(1)

Circulation. 2004;109:1101-1107.

(c) 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Explaining the Decline in Coronary Heart Disease Mortality in England and Wales Between 1981 and 2000

Belgin Unal, MD, MPH; Julia Alison Critchley, DPhil; Simon Capewell, MD

From the Department of Public Health, University of Liverpool, England (B.U., J.A.C., S.C.), and the Department of Public Health, Dokuz Eylul University School of Medicine, Izmir, Turkey (B.U.).

Correspondence to Dr Belgin Unal, Dokuz Eylul University School of Medicine Department of Public Health, Izmir, Turkey. E-mail belgina@liv.ac.uk

Received August 6, 2003; revision received October 18, 2003; accepted October 18, 2003.

Background- Coronary heart disease mortality rates have been decreasing in the United Kingdom since the 1970s. Our study aimed to examine how much of the decrease in England and Wales between 1981 and 2000 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors.

Methods and Results- The IMPACT mortality model was used to combine and analyze data on uptake and effectiveness of cardiological treatments and risk factor trends in England and Wales. The main data sources were published trials and meta-analyses, official statistics, clinical audits, and national surveys. Between 1981 and 2000, coronary heart disease mortality rates in England and Wales decreased by 62% in men and 45% in women 25 to 84 years old. This resulted in 68 230 fewer deaths in 2000. Some 42% of this decrease was attributed to treatments in individuals (including 11% to secondary prevention, 13% to heart failure treatments, 8% to initial treatments of acute myocardial infarction, and 3% to hypertension treatments) and 58% to population risk factor reductions (principally smoking, 48%; blood pressure, 9.5%; and cholesterol, 9.5%). Adverse trends were seen for physical activity, obesity and diabetes.

Conclusions- More than half the coronary heart disease mortality decrease in Britain between 1981 and 2000 was attributable to reductions in major risk factors, principally smoking. This emphasizes the importance of a comprehensive strategy that promotes primary prevention, particularly for tobacco and diet, and that maximizes population coverage of effective treatments, especially for secondary prevention and heart failure. These findings may be cautiously generalizable to the United States and other developed countries. *

 References 1(2)

Lancet. 1998 May 2;351(9112):1308-11.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9643792

Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure.

Bernardi L, Spadacini G, Bellwon J, Hajric R, Roskamm H, Frey AW.

Department of Internal Medicine, IRCCS S Matteo, University of Pavia, Italy. LBern1ps@ipv36.unipv.it

BACKGROUND: In chronic heart failure (CHF), impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity. We investigated the effect of breathing rate on oxygen saturation and other respiratory indices. METHODS: Arterial oxygen saturation (SaO2) and respiratory indices were recorded during spontaneous breathing (baseline) and during controlled breathing at 15, six, and three breaths per min in 50 patients with CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min. Respiratory indices were recorded before training, at the end of training, and 1 month after training. FINDINGS: During spontaneous breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4] vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing rates in patients with CHF. Compared with baseline, minute ventilation increased at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine CHF patients who had 1 month of respiratory training, resting SaO2 increased from 92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no changes in the respiratory indices in the patients who did not have respiratory training. INTERPRETATION: Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF.*

 References 1(3)

Circulation. 2002;105:143.)

(c) 2002 American Heart Association, Inc.

Brief Rapid Communications

Slow Breathing Increases Arterial Baroreflex Sensitivity in Patients With Chronic Heart Failure

Luciano Bernardi, MD; Cesare Porta, MD; Lucia Spicuzza, MD; Jerzy Bellwon, MD; Giammario Spadacini, MD; Axel W. Frey, MD; Leata Y.C. Yeung, MD; John E. Sanderson, MD; Roberto Pedretti, MD; Roberto Tramarin, MD

From the Department of Internal Medicine, University of Pavia and IRCCS Ospedale S Matteo, (L.B., C.P.), Pavia, Italy; the Institute of Respiratory Diseases, University of Catania (L.S.), Catania, Italy; First Department of Cardiology, University of Gdansk (J.B.), Gdansk, Poland; Herz-Zentrum (G.M., A.W.F.), Bad Krozingen, Germany; the Chinese University of Hong Kong, Prince of Wales Hospital (L.Y.C.Y., J.E.S.), Hong Kong SAR; the Department of Cardiology, IRCCS Fondazione Salvatore Maugeri, Centro Medico Tradate (R.P.), Tradate, Italy; and the Department of Cardiology, IRCCS Fondazione Salvatore Maugeri, Centro Medico Pavia (R.T.), Pavia, Italy.

Correspondence to Luciano Bernardi, MD, Clinica Medica 1, Universita' di Pavia, IRCCS Ospedale S Matteo, 27100 Pavia, Italy. E-mail lbern1ps@unipv.it

Background- It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction.

Methods and Results- We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in 81 patients with stable (2 weeks) CHF (age, 58±1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15]) and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from 9.4±0.7 to 13.8±1.0 ms/mm Hg, P<0.0025) and in CHF patients (from 5.0±0.3 to 6.1±0.5 ms/mm Hg, P<0.0025), which correlated with the value obtained during spontaneous breathing (r=+0.202, P=0.047). In addition, systolic and diastolic blood pressure decreased in CHF patients (systolic, from 117±3 to 110±4 mm Hg, P=0.009; diastolic, from 62±1 to 59±1 mm Hg, P=0.02).

Conclusions- These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.

Key Words: baroreflex • heart failure • heart rate • blood pressure • respiration *

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Circulation. 2003;108:2757.)

(c) 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Relation Between Progression and Regression of Atherosclerotic Left Main Coronary Artery Disease and Serum Cholesterol Levels as Assessed With Serial Long-Term (9-18 Months) Follow-Up Intravascular Ultrasound

Clemens von Birgelen, MD, PhD; Marc Hartmann, MD; Gary S. Mintz, MD; Dietrich Baumgart, MD; Axel Schmermund, MD; Raimund Erbel, MD

From the Department of Cardiology, Essen University, Essen, Germany (C.v.B., M.H., D.B., A.S., R.E.); the Department of Cardiology, Medisch Spectrum Twente, Enschede, the Netherlands (C.v.B.); and the Cardiovascular Research Foundation, New York, NY (G.S.M.).

Correspondence to Dr Clemens von Birgelen, Medisch Spectrum Twente, Enschede Hospital, Cardiology Department, Ariensplein 1, 7511 JX Enschede, The Netherlands. E-mail von.birgelen@freeler.nl

Received May 28, 2003; revision received September 4, 2003; accepted September 8, 2003.

Background- The relation between serum lipids and risk of coronary events has been established, but there are no data demonstrating directly the relation between serum low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol versus serial changes in coronary plaque dimensions.

Methods and Results- We performed standard analyses of serial intravascular ultrasound (IVUS) studies of 60 left main coronary arteries obtained 18.3±9.4 months apart to evaluate progression and regression of mild atherosclerotic plaques in relation to serum cholesterol levels. Overall, there was (1) a positive linear relation between LDL cholesterol and the annual changes in plaque plus media (P&M) cross-sectional area (CSA) (r=0.41, P<0.0001) with (2) an LDL value of 75 mg/dL as the cutoff when regression analysis predicted on average no annual P&M CSA increase; (3) an inverse relation between HDL cholesterol and annual changes in P&M CSA (r=-0.30, P<0.02); (4) an inverse relation between LDL cholesterol and annual changes in lumen CSA (r=-0.32, P<0.01); and (5) no relation between LDL and HDL cholesterol and the annual changes in total arterial CSA (remodeling). Despite similar baseline IVUS characteristics, patients with an LDL cholesterol level  <120 mg/dL showed more annual P&M CSA progression and lumen reduction than patients with lower LDL cholesterol.

Conclusions- There is a positive linear relation between LDL cholesterol and annual changes in plaque size, with an LDL value of 75 mg/dL predicting, on average, no plaque progression. HDL cholesterol shows an inverse relation with annual changes in plaque size.

Key Words: ultrasonics • coronary disease • cholesterol • lipids   *

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American Journal of Clinical Nutrition, Vol. 74, No. 1, 1-2, July 2001

(c) 2001 American Society for Clinical Nutrition

Editorial

The public health implications of the Dietary Approaches to Stop Hypertension Trial 1,2

For study purposes it is highly recommended to go to the original article at http://www.ajcn.org/cgi/content/full/74/1/1 and use references and their links to online free texts

George Lburn Black¹

1 From the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.

2 Reprints not available. Address correspondence to GL Blackburn, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Autumn Street, Kennedy 152, Boston, MA 02215. E-mail: gblackbu@caregroup.harvard.edu. RFN2

The Dietary Approaches to Stop Hypertension (DASH) Trial was designed to assess the relation between modification of dietary patterns and hypertension (1, 2). DASH provides evidence that existing dietary recommendations can produce concrete health results in a relatively healthy but sedentary population in which 50% of the participants were women and 60% were African American. Obarzanek et al (3) applied the Framingham risk equation (4) to the results of their study published in this issue of the Journal to estimate 10-y risk of coronary heart disease (CHD) in subjects consuming the recommended DASH diet. The results showed a 12.1% decreased risk of CHD in the participants consuming the DASH diet compared with a slightly increased risk in those consuming the control diet. The decrease was achieved in the absence of changes in weight or physical activity. Reductions in blood lipids were greater in men than in women, whereas the lipid response to diet did not differ significantly between African Americans and non-African Americans.

Data from DASH and other clinical trials offer the most significant evidence to date of the role of diet in health promotion, disease prevention, and disease treatment (5-7). These studies underscore the messages in the new Dietary Guidelines for Americans (8). The DASH diet and similar dietary patterns that include low-fat dairy products and a high intake of fruit, vegetables, and fiber provide important guidelines for public health policy (9, 10). Other lifestyle factors-such as physical activity levels, annual physical exams, immunizations, monitoring of vital signs, and other preventive health measures-might also affect outcomes. This may be particularly true for exercise, which can be expected to raise HDL cholesterol and lower triacylglycerol, results not achieved by the DASH diet alone. Weight loss can also be expected to potentiate the outcomes.

The lipid biomarkers of CHD risk are well established (4, 6, 7, 11), as are the salubrious effects of diets that include low-fat dairy products and certain fruit and vegetables, including legumes, potatoes, juices, apples, bananas, oranges, lettuce, spinach, string beans, and tomatoes. Absence of information on various fruit and vegetables, however, may be especially problematic if only certain types and diversities confer protection, eg, spinach, Brussels sprouts, broccoli, and string beans, which are particularly nutrient dense and require little insulin for their digestion and metabolism.

Dietary patterns are influenced by cultural, ethnic, and environmental factors, including the availability of foods, the ability to purchase and prepare foods, and food industry advertising. Dietary patterns are also not readily altered, and the major limitation of the DASH study is the questionable ability of most persons to maintain dietary changes in the long term.

The DASH diet requires twice the average daily servings of fruit, vegetables, and dairy products; one-third the usual intake of beef, pork, and ham; one-half the typical use of fats, oils, and salad dressings; and one-quarter the ordinary number of snacks and sweets. It also requires education for lactose-intolerant individuals on the use of lactase enzyme products and behavior modification to help change lifelong eating habits. The volume of food consumed from the 5 major food groups of the DASH diet is 1.94 kg (68.5 oz), whereas only 51 g (1.8 oz) comes from fats and sugars. This is twice the volume of healthful food and a fraction of the energy-dense, nutrient-poor junk food found in a typical Western diet (1, 10, 12).

According to public health researchers, those who make small, incremental changes in their diet over time have the highest probability of success. Recommendations include considering meat as just one part of a meal; centering food choices around carbohydrates such as pasta, rice, beans, or vegetables; and replacing traditional snacks and desserts with fruit or low-fat, low-energy foods such as sugarless gelatin. Portion-controlled foods and liquid meal replacement represent a new approach to healthful eating (5-7, 11).

Current clinical studies targeted to changes in diet and exercise patterns stress the importance of these community and individual challenges. However, long-term results do not bode well for healthful diets according to the results of DASH (9, 10). Nevertheless, DASH and other dietary pattern trials have provided significant knowledge on the role of diet in preventing chronic disease. It is incumbent on us to use that knowledge in the interest of public health (13).

The need to develop a simple, modern diet as effective as the DASH diet is one of the major challenges facing food technologists and nutrition scientists (13, 14). It is also an extraordinary opportunity for improving public health by broadening the appeal and use of scientifically sound functional foods. Tucker et al (15), for example, describes relations among consumption of whole grains, vegetables, fruit, and fish and the inverse association of these foods with meat. Fung et al (10) advanced this approach by examining the relation between 2 dietary patterns, a so-called prudent pattern and a Western pattern, and biomarkers of cardiovascular disease risk. This scientific approach, which used factor analysis, provided added evidence that dietary patterns can be related to measures of health. Other studies that used cluster analysis reached the same conclusion, particularly when the cohort was well defined and restricted to one population. The Healthy Eating Index, a comprehensive measure of diet quality, combines multiple aspects of diet in relation to guidelines into a single score (16).

We need to develop simple and clear food-selection tools that will meet the recommendations of the Dietary Guidelines for Americans. Evidence from DASH and similar controlled studies provides proof of the value of scientifically sound food selection, but there is a lack of science on which community strategies or individual interventions can be based. Our diverse society requires innovation in food delivery, convenience, and culture-changes that will deliver measurable improvements in compliance to new dietary patterns and in quality of life.

REFERENCES

1. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336:1117-24.

2. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001;344:3-10.

3. Obarzanek E, Sacks FM, Vollmer WM, et al. Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial. Am J Clin Nutr 2001;74:80-9.

4. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

5. Metz JA, Stern JS, Kris-Etherton P, et al. A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction. Arch Intern Med 2000;160:2150-8.

6. Chait A, Malinow MR, Nevin DN, et al. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease. Am J Clin Nutr 1999;70:881-7.

7. Haynes RB, Kris-Etherton P, McCarron DA, et al. Nutritionally complete prepared meal plan to reduce cardiovascular risk factors: a randomized clinical trial. J Am Diet Assoc 1999;99:1077-83.[Medline]

8. US Department of Health and human Services, US Department of Agriculture. Dietary guidelines for Americans. 5th ed. Washington, DC: US Government Printing Office, 2000.

9. Kant AK, Schatzkin A, Graubard BI, Schairer C. A prospective study of diet quality and mortality in women. JAMA 2000;283: 2109-15.

10. Fung TT, Rimm EB, Spiegelman D, et al. Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am J Clin Nutr 2001;73:61-7.

11. Ditschuneit HH, Flechtner-Mors M, Johnson TD, Adler G. Metabolic and weight-loss effects of a long-term dietary intervention in obese patients. Am J Clin Nutr 1999;69:198-204.

12. Kant AK. Consumption of energy-dense, nutrient-poor foods by adult Americans: nutritional and health implications. The third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2000;72:929-36.

13. Blackburn GL. Functional foods in the prevention and treatment of disease: significance of the Dietary Approaches to Stop Hypertension Study. Am J Clin Nutr 1997;66:1067-71.

14. French SA, Jeffery RW, Story M, et al. Pricing and promotion effects on low-fat vending snack purchases: the CHIPS Study. Am J Public Health 2001;91:112-7.

15. Tucker KL, Dallal GE, Rush D. Dietary patterns of elderly Boston-area residents defined by cluster analysis. J Am Diet Assoc 1992;92: 1487-91.

Kennedy ET, Phis J, Carlson S, Fleming K. The Healthy Eating Index: design and application. J Am Diet Assoc 1995;95:1103-8. *

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Prev Med. 2000 Apr;30(4):277-81                                                                    

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10731455&dopt=Citation

Training effects of accumulated daily stair-climbing exercise in previously sedentary young women.

Boreham CA, Wallace WF, Nevill A.

Sports Studies, University of Ulster at Jordanstown, Jordanstown, Country Antrim, BT37 OQB, United Kingdom. ca.boreham@ulst.ac.uk

BACKGROUND: The health and fitness benefits associated with short, intermittent bouts of exercise accumulated throughout the day have been seldom investigated. Stair climbing provides an ideal model for this purpose. METHODS: Twenty-two healthy female volunteers (18-22 years) were randomly assigned to control (N = 10) or stair-climbing (N = 12) groups. Stair climbers then underwent a 7-week stair-climbing program, progressing from one ascent per day in week 1 to six ascents per day in weeks 6 and 7, using a public access staircase (199 steps). Controls were instructed to maintain their normal lifestyle. Standardized stair-climbing tests were administered to both groups immediately before and after the program. Each paced ascent lasted 135 s, during which oxygen uptake (VO(2)) and heart rate (HR) were monitored continuously. Blood lactate concentration was also measured immediately following each test ascent. Fasting blood samples from before and after the program were analyzed for serum lipids. Data were analyzed using a two-way ANOVA with repeated measures. RESULTS: Relative to the insignificant changes in the control group, the stair-climbing group displayed a rise in HDL cholesterol concentration (P<0.05) and a reduced total:HDL ratio (P<0.01) over the course of the program. VO(2) and HR during the stair-climbing test were also reduced, as was blood lactate (all P<0.01). CONCLUSION: A short-term stair-climbing program can confer considerable cardiovascular health benefits on previously sedentary young women, lending credence to the potential public health benefits of this form of exercise. Copyright 2000 American Health Foundation and Academic Press.    *

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New England Journal of Medicine Volume 342:1392-1398 May 11, 2000 Number 19

Beneficial Effects of High Dietary Fiber Intake in Patients with Type 2 Diabetes Mellitus

Manisha Chandalia, M.D., Abhimanyu Garg, M.D., Dieter Lutjohann, Ph.D., Klaus von Bergmann, M.D., Scott M. Grundy, M.D., Ph.D., and Linda J. Brinkley, R.D.

http://content.nejm.org/cgi/content/abstract/342/19/1392?firstpage=1392&volume=342&sendit=GO&searchid=1091433117318_830&FIRSTINDEX=0&volume=342&firs tpage=1392&journalcode=nejm

For comment http://www.medscape.com/viewarticle/418629

ABSTRACT

Background The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial.

Methods In a randomized, crossover study, we assigned 13 patients with type 2 diabetes mellitus to follow two diets, each for six weeks: a diet containing moderate amounts of fiber (total, 24 g; 8 g of soluble fiber and 16 g of insoluble fiber), as recommended by the American Diabetes Association (ADA), and a high-fiber diet (total, 50 g; 25 g of soluble fiber and 25 g of insoluble fiber) containing foods not fortified with fiber (unfortified foods). Both diets, prepared in a research kitchen, had the same macronutrient and energy content. We compared the effects of the two diets on glycemic control and plasma lipid concentrations.

Results Compliance with the diets was excellent. During the sixth week of the high-fiber diet, as compared with the sixth week of the ADA diet, mean daily preprandial plasma glucose concentrations were 13 mg per deciliter (0.7 mmol per liter) lower (95 percent confidence interval, 1 to 24 mg per deciliter [0.1 to 1.3 mmol per liter]; P=0.04) and mean daily urinary glucose excretion was 1.3 g lower (median difference, 0.23 g; 95 percent confidence interval, 0.03 to 1.83; P=0.008). The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations, which were measured every two hours, by 10 percent (P=0.02) and 12 percent (P=0.05), respectively. The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent (P=0.02), triglyceride concentrations by 10.2 percent (P=0.02), and very-low-density lipoprotein cholesterol concentrations by 12.5 percent (P=0.01).

Conclusions A high intake of dietary fiber, particularly of the soluble type, above the level recommended by the ADA, improves glycemic control, decreases hyperinsulinemia, and lowers plasma lipid concentrations in patients with type 2 diabetes.

Source Information

From the Department of Internal Medicine (M.C., A.G., S.M.G., L.J.B.) and the Center for Human Nutrition (A.G., S.M.G.), University of Texas Southwestern Medical Center, Dallas; the Department of Veterans Affairs Medical Center, Dallas (M.C., A.G., S.M.G.); and the Department of Clinical Pharmacology, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany (D.L., K.B.).

Address reprint requests to Dr. Garg at the Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390.     *

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December 2004  J Am Dietetic Assoc Volume 104 Number 12

Diets lower in folic acid and carotenoids are associated with the coronary disease epidemic in Central and Eastern Europe

Sonja L. Connor, MS, RD *

Lila S. Ojeda, MS, RD

Gary Sexton, PhD

Gerdi Weidner, PhD

William E. Connor, MD

Abstract

Objective To test our hypothesis that lower intakes of previously identified cardioprotective nutrients would be associated with the coronary epidemic in Central and Eastern Europe.

Design We conducted a survey of coronary mortality in 16 countries and diet in 19 countries.

Subjects/setting Countries were placed in four groups with different cultural patterns (Central and Eastern Europe, including Russia; Western Europe and the United States; Mediterranean; and Asian).

Main outcome measures Independent predictors of coronary mortality.

Statistical analyses performed Means and standard deviations were calculated, and analysis of variance with Bonferroni post hoc tests and backward elimination regression analysis was conducted.

Results Coronary mortality was highest in Central and Eastern Europe followed by Western Europe and the United States, the Mediterranean countries, and Asia (Japan). The model with folate, fiber, and n-6/n-3 fatty acids explained the majority of variation in coronary mortality (men 86%, women 90%). Most of the variation was explained by folate (men 61%, women 62%). The picture is complicated by the fact that folate, lutein/zeaxanthin, and beta-carotene were highly intercorrelated (r=0.87 to 0.99).

Conclusions A diet low in foods containing folate and carotenoids (beta-carotene and lutein/zeaxanthin) may be a major contributing factor to increased coronary risk observed in the countries of Central and Eastern Europe.

*Address correspondence to: Sonja L. Connor, MS, RD, Research Associate Professor, Department of Medicine, Oregon Health and Science University: L465, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3098.

Email address: connors@ohsu.edu (Sonja L. Connor)

Copyright (c) by American Dietetic Association doi: 10.1016/j.jada.2004.09.023

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Circulation. 2004;110:1236-1244.)

(c) 2004 American Heart Association, Inc.

Original Articles

Explaining the Increase in Coronary Heart Disease Mortality in Beijing Between 1984 and 1999

Julia Critchley, MSc, DPhil; Jing Liu, MD, MPH; Dong Zhao, MD, PhD; Wang Wei, MD; Simon Capewell, FRCPE

From International Health Research Group (J.C.), Liverpool School of Tropical Medicine, Liverpool, UK; Department of Epidemiology (J.L., D.Z., W.W.), Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing, China; and Department of Public Health (S.C.), University of Liverpool, Liverpool, UK.

Correspondence to Dr Julia Critchley, International Health Research Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. E-mail juliac@liverpool.ac.uk

Received January 8, 2004; revision received May 12, 2004; accepted May 21, 2004.

Background- Coronary heart disease (CHD) mortality is rising in many developing countries. We examined how much of the increase in CHD mortality in Beijing, China, between 1984 and 1999 could be attributed to changes in major cardiovascular risk factors and assessed the impact of medical and surgical treatments.

Methods and Results- A validated, cell-based mortality model synthesized data on (1) patient numbers, (2) uptake of specific medical and surgical treatments, (3) treatment effectiveness, and (4) population trends in major cardiovascular risk factors (smoking, total cholesterol, blood pressure, obesity, and diabetes). Main data sources were the WHO MONICA and Sino-MONICA studies, the Chinese Multi-provincial Cohort Study, routine hospital statistics, and published meta-analyses. Age-adjusted CHD mortality rates increased by 50% in men and 27% in women (1608 more deaths in 1999 than expected by application of 1984 rates). Most of this increase (77%, or 1397 additional deaths) was attributable to substantial rises in total cholesterol levels (more than 1 mmol/L), plus increases in diabetes and obesity. Blood pressure decreased slightly, whereas smoking prevalence increased in men but decreased substantially in women. In 1999, medical and surgical treatments in patients together prevented or postponed 642 deaths, mainly from initial treatments for acute myocardial infarction (41%), hypertension (24%), angina (15%), secondary prevention (11%), and heart failure (10%). Multiway sensitivity analyses did not greatly influence the results.

Conclusions- Much of the dramatic CHD mortality increases in Beijing can be explained by rises in total cholesterol, reflecting an increasingly "Western" diet. Without cardiological treatments, increases would have been even greater.

Key Words: coronary disease  mortality  risk factors  prevention *

 (A10)

Circulation. 2001;104:2018.)

(c) 2001 American Heart Association, Inc.

Reducing Emotional Distress Improves Prognosis in Coronary Heart Disease 9-Year Mortality in a Clinical Trial of Rehabilitation

Johan Denollet, PhD; Dirk L. Brutsaert, MD

From the Department of Clinical Health Psychology, Tilburg University, the Netherlands (J.D.), and the Center for Cardiac Rehabilitation, University Hospital of Antwerp, Belgium (J.D., D.L.B.).

Correspondence to Johan Denollet, PhD, Clinical Health Psychology, Room P508, Tilburg University, Warandelaan, 2, PO Box 90153, 5000 LE Tilburg, the Netherlands. E-mail j.denollet@kub.nl

Background- The impact of treating emotional distress on prognosis in coronary heart disease (CHD) has not been documented convincingly. We tested the hypothesis that treatment-related changes in emotional distress may explain the beneficial effect of rehabilitation on prognosis.

Methods and Results- In this nonrandomized clinical trial, 150 men with CHD participated in rehabilitation (n=78) or received standard medical care (n=72). There were no differences between rehabilitation and control patients with regard to left ventricular ejection fraction (LVEF) or standard care. End points were reduction in distress after 3 months and mortality after 9 years. At the end of the 3-month trial, 64 patients (43%) reported improvement and 22 (15%) reported deterioration in negative affect. Rehabilitation patients improved more (P=0.004) and deteriorated less (P=0.001) than control patients; rehabilitation was effective in reducing distress. After 9 years of follow-up, 15 patients had died (13 cardiac and 2 cancer deaths). Mortality was associated with LVEF 50% (P=0.038) and deterioration in negative affect (P=0.007). Rate of death was 17% (12/72) for control patients versus 4% (3/78) for rehabilitation patients (P=0.009); rehabilitation was effective in reducing mortality. LVEF 50% (OR 3.2; 95% CI 1.1 to 9.8; P=0.041) and rehabilitation (OR 0.2; 95% CI 0.1 to 0.7; P=0.016) were independent predictors of mortality. Rehabilitation warded off the deleterious effect of deterioration in negative affect on prognosis.

Conclusions- Deterioration in negative affect is associated with a high long-term mortality risk. Warding off deterioration in negative affect is a mechanism that may explain the beneficial effect of comprehensive rehabilitation on prognosis in patients with CHD.

Key Words: myocardial infarction • mortality • stress • depression • trials *

 (A11)

Circulation. 2004;110:3599-3603.

(c) 2004 American Heart Association, Inc.

Vascular Medicine

Postprandial Hypertriglyceridemia Increases Circulating Levels of Endothelial Cell Microparticles

Alexandre C. Ferreira, MD; Arley A. Peter, MD; Armando J. Mendez, PhD; Joaqu¡n J. Jimenez, MD; Lucia M. Mauro; Julio A. Chirinos, MD; Reyan Ghany, MD; Salim Virani, MD; Santiago Garcia, MD; Lawrence L. Horstman; Joshua Purow, MD; Wenche Jy, PhD; Yeon S. Ahn, MD; Eduardo de Marchena, MD

From the University of Miami School of Medicine, Cardiovascular Center (A.C.F., A.A.P., J.A.C., R.G., S.V., S.G., L.L.H., J.P., E.D.M.), Diabetes Research Institute (A.J.M.), and Wallace H. Coulter Platelet Laboratory (J.J.J., L.M.M., W.J., Y.S.A.), Miami, Fla.

Correspondence to Alexandre Ferreira, MD, Director, Coronary Care Unit, Department of Medicine, Division of Cardiology, PO Box 016960, Miami, FL 33101. E-mail aferreir@med.miami.edu

Received April 15, 2004; revision received August 3, 2004; accepted August 12, 2004.

Background- This study evaluated a possible relationship between levels of endothelial microparticles (EMPs), known to be a sensitive indicator of endothelial disturbance, and changes in postprandial lipid levels in healthy volunteers after a low- or high-fat meal.

Methods and Results- Eighteen healthy subjects without known cardiovascular risk factors were evaluated. Lipid and EMP levels were measured before and 1 and 3 hours after a single low- or high-fat isocaloric meal. The low-fat meal had no significant postprandial effect on EMPs or lipids compared with fasting levels. In contrast, a single high-fat meal significantly increased EMP levels after 1 and 3 hours, from 389±54 (thousands per milliliter) when fasting to 541±139 (P=0.0002) and 677±159 (P<0.0001), respectively, and correlated with a postprandial elevation in serum triglycerides.

Conclusions- A single high-fat meal led to a significant elevation of plasma EMP levels in healthy, normolipidemic subjects and correlated with a postprandial elevation of serum triglycerides. EMPs may be an indirect marker of endothelial dysfunction or injury induced by postprandial triglyceride-rich lipoproteins.

Key Words: hypertriglyceridemia  endothelium  microparticles *

  (A12)

For study purposes it is recommended you link to the original abstract and then use links to the rest of that particular issue / volume of the journal http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12831834

Brain Behav Immun. 2003 Aug;17(4):310-5.

Psychological factors correlate meaningfully with percent-monocytes among acute coronary syndrome patients.

Gidron Y, Armon T, Gilutz H, Huleihel M.

Department of Sociology of Health, Faculty of Health Sciences, Ben-Gurion University, Be'er-Sheva 84105, Israel. yorig@bgumail.bgu.ac.il

Recent research demonstrates the importance of inflammatory parameters in the etiology and prognosis of the acute coronary syndrome (ACS). This study explored relations between psychological factors and immunological parameters routinely measured among ACS patients. Forty-two ACS patients completed questionnaires assessing perceived-control, emotional support, hostility, and life-events 2-4 days after hospitalization. Data on total leukocytes and percentages (%) of monocytes, %neutrophils, and %lymphocytes upon admission to hospital were collected from computerized medical charts as well as various biomedical information and risk-factors (e.g., diagnosis, left-ventricle-LV functioning, smoking, and hypertension). Of all significant biomedical variables, LV-function and arrival-time correlated uniquely with total leukocytes. Controlling for LV-function and arrival-time, hostility and life-events positively correlated with %monocytes, and perceived-control and emotional-support inversely correlated with %monocytes. Emotional-support was positively correlated and life-events were negatively correlated with %neutrophils. Macrophages play a pivotal role in plaque instability, the trigger of an ACS. This initiating role, and our finding of a relationship between recruitment of monocytes and a poor psychosocial profile, predictive of ACS, are consistent with a PNI component in the pathophysiology of ACS.    *

 (A13)

J Am Coll Cardiol. 2003 Sep 3;42(5):861-872.

Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure.

Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, Kempf W, Schubert A, Schuler G, Hambrecht R.

Universitat Leipzig, Herzzentrum GmbH, Department of Internal Medicine & Cardiology, Strumpellstrasse 39, 04289 Leipzig, Germany.

OBJECTIVES: The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure (CHF).BACKGROUND: Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase (iNOS) in the myocardium and peripheral skeletal muscles has been described in CHF. METHODS: Twenty male patients with stable CHF (left ventricular ejection fraction 25 +/- 2%; age 54 +/- 2 years) were randomized to a training group (n = 10) or a control group (n = 10). At baseline and after six months, serum samples and vastus lateralis muscle biopsies were obtained. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1-beta levels were measured by enzyme-linked immunosorbent assay, local cytokine, and iNOS expression by real-time polymerase chain reaction. RESULTS: Exercise training improved peak oxygen uptake by 29% in the training group (from 20.3 +/- 1.0 to 26.1 +/- 1.5 ml/kg. min; p < 0.001 vs. control group). While serum levels of TNF-alpha, IL-6, and IL-1-beta remained unaffected by training, local skeletal muscle TNF-alpha decreased from 1.9 +/- 0.4 to 1.2 +/- 0.3 relative U (p < 0.05 for change vs. control group), IL-6 from 71.3 +/- 16.5 to 41.3 +/- 8.8 relative U (p < 0.05 vs. begin), and IL-1-beta from 2.7 +/- 1.1 to 1.4 +/- 0.6 relative U (p = 0.02 vs. control group). Exercise training also reduced local iNOS expression by 52% (from 6.3 +/- 1.2 to 3.0 +/- 1.0 relative U; p = 0.007 vs. control group). CONCLUSIONS: Exercise training significantly reduced the local expression of TNF-alpha, IL-1-beta, IL-6, and iNOS in the skeletal muscle of CHF patients. These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.

COMMENT

Anti-Inflammatory Effects of Exercise May Lessen CHF-Related Cardiac Skeletal Muscle Wasting

Aerobic exercise reduces levels of inflammatory cytokines in skeletal muscle of patients with chronic heart failure (CHF), researchers report in the September 3rd issue of the Journal of the American College of Cardiology.

These local anti-inflammatory effects of exercise may attenuate skeletal muscle wasting seen in patients with CHF.

"For patients with stable CHF, regular aerobic exercise training should not be regarded as rehabilitation only, but as a continuing treatment with the potential to modify the underlying disease process," Dr. Stephan Gielen of the University of Leipzig Heart Center in Germany said in a statement.

Dr. Gielen and colleagues randomly assigned 20 men with stable CHF to a control group or to an exercise-training group for 6 months. Men in the training group participated in group workouts and rode a stationary bicycle daily for 20 minutes at workloads corresponding to 70% of maximal oxygen uptake during symptom-limited exercise.

At baseline, local expression of TNF-alpha, IL-1-beta, and IL-6 was significantly increased in skeletal muscle relative to serum levels of these cytokines, which were only slightly higher than normal.

Six months of regular exercise led to a significant reduction in skeletal muscle TNF-alpha, IL-1-beta, and IL-6, while serum levels of these cytokines remained virtually unchanged. Specifically, TNF-alpha fell from 1.9 to 1.2 U (p < 0.05 for change vs. control), IL-1-beta from 2.7 to 1.4 U (p = 0.02 vs. control), and IL-6 from 71.3 to 41.3 U (p < 0.05 vs. baseline).

Exercise training also reduced local inducible nitric oxide synthase (iNOS) expression by 52%.

There was no change in TNF-alpha, IL-1-beta, and IL-6 or iNOS in the control group.

Consistent with previous reports, exercise training also improved peak oxygen uptake by 29%.

"Taken together, these results indicate that long-term aerobic endurance training in CHF patients has anti-inflammatory effects on the skeletal muscle," Dr. Gielen and colleagues write. "These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF.*

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Circulation. 2003;108:530.)

(c) 2003 American Heart Association, Inc.

Effect of Different Intensities of Exercise on Endothelium-Dependent Vasodilation in Humans Role of Endothelium-Dependent Nitric Oxide and Oxidative Stress

Chikara Goto, RPT, MS; Yukihito Higashi, MD, PhD; Masashi Kimura, MD; Kensuke Noma, MD; Keiko Hara, MD; Keigo Nakagawa, MD; Mitsutoshi Kawamura, RPT, MS; Kazuaki Chayama, MD, PhD; Masao Yoshizumi, MD, PhD; Isao Nara, RPT, PhD

From the Program in Physical Therapy Health Sciences, School of Medicine (C.G., M.K., I.N.), Department of Cardiovascular Physiology and Medicine (Y.H., M.Y.), Department of Medicine and Molecular Science (K. Noma, M.K., K.H., K. Nakagawa, K.C.), Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Correspondence to Yukihito Higashi, MD, PhD, FAHA, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi@hiroshima-u.ac.jp

Received June 11, 2002; de novo received February 19, 2003; revision received May 5, 2003; accepted May 5, 2003.

Background- Aerobic exercise enhances endothelium-dependent vasodilation in hypertensive patients, patients with chronic heart failure, and healthy individuals. However, it is unclear how the intensity of exercise affects endothelial function in humans. The purpose of the present study was to determine the effects of different intensities of exercise on endothelium-dependent vasodilation in humans.

Methods and Results- We evaluated the forearm blood flow responses to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after different intensities of exercise (mild, 25% O2max; moderate, 50% O2max; and high, 75% O2max; bicycle ergometers, 30 minutes, 5 to 7 times per week for 12 weeks) in 26 healthy young men. Forearm blood flow was measured using a mercury-filled Silastic strain-gauge plethysmograph. Twelve weeks of moderate-intensity exercise, but not mild- or high-intensity exercise, significantly augmented acetylcholine-induced vasodilation (7.5±2.4 to 11.4±5.8 mL/min per 100 mL tissue; P<0.05). No intensity of aerobic exercise altered isosorbide dinitrate-induced vasodilation. The administration of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished the moderate-intensity exercise-induced augmentation of the forearm blood flow response to acetylcholine. High-intensity exercise increases plasma concentrations of 8-hydroxy-2'-deoxyguanosine (from 6.7±1.1 to 9.2±2.3 ng/mL; P<0.05) and serum concentrations of malondialdehyde-modified low-density lipoprotein (from 69.0±19.5 to 82.4±21.5 U/L; P<0.05), whereas moderate exercise tended to decrease both indices of oxidative stress.

Conclusions- These findings suggest that moderate-intensity aerobic exercise augments endothelium-dependent vasodilation in humans through the increased production of nitric oxide and that high-intensity exercise possibly increases oxidative stress.     *

 (A15)

Circulation. 2003;108:292.)

(c) 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Variability of Phase Shift Between Blood Pressure and Heart Rate Fluctuations A Marker of Short-Term Circulation Control

Josef Halámek, PhD; Tomá Kára, MD; Pavel Jurák, PhD; Miroslav Souek, MD, PhD; Darrel P. Francis, MD, MRCP; L. Ceri Davies, MD, MRCP; Win K. Shen, MD, PhD; Andrew J.S. Coats, DM, FRCP; Miroslav Novák, MD, PhD; Zuzana Nováková, MD, PhD; Roman Panovsk, MD; Jií Toman, MD, PhD; Josef umbera, MD, PhD; Virend K. Somers, MD, PhD

From the Institute of Scientific Instruments (J.H., P.J.), Academy of Sciences; St Anne's University Hospital (T.K., M.S., M.N., R.P., J.T., J.S.); and the Faculty of Medicine (Z.N.), Masaryk University, Brno, Czech Republic; Mayo Clinic (T.K., W.K.S., V.K.S.), Rochester, Minn; Chelsea & Westminster Hospital (D.P.F.), London; Colchester General Hospital (L.C.D.), Colchester; and the National Heart & Lung Institute (A.J.S.C.), London, UK.

Reprint requests to Josef Halámek, PhD, Institute of Scientific Instruments, AS CR, Královopolská 147, 612 64 Brno, Czech Republic. E-mail josef@isibrno.cz

Background- We postulated that the variability of the phase shift between blood pressure and heart rate fluctuation near the frequency of 0.10 Hz might be useful in assessing autonomic circulatory control.

Methods and Results- We tested this hypothesis in 4 groups of subjects: 28 young, healthy individuals; 13 elderly healthy individuals; 25 patients with coronary heart disease; and 19 patients with a planned or implanted cardioverter-defibrillator (ICD recipients). Data from 5 minutes of free breathing and at 2 different, controlled breathing frequencies (0.10 and 0.33 Hz) were used. Clear differences (P<0.001) in variability of phase were evident between the ICD recipients and all other groups. Furthermore, at a breathing frequency of 0.10 Hz, differences in baroreflex sensitivity (P<0.01) also became evident, even though these differences were not apparent at the 0.33-Hz breathing frequency.

Conclusions- The frequency of 0.10 Hz represents a useful and potentially important one for controlled breathing, at which differences in blood pressure-RR interactions become evident. These interactions, whether computed as a variability of phase to define stability of the blood pressure-heart rate interaction or defined as the baroreflex sensitivity to define the gain in heart rate response to blood pressure changes, are significantly different in patients at risk for sudden arrhythmic death. In young versus older healthy individuals, only baroreflex gain is different, with the variability of phase being similar in both groups. These measurements of short-term circulatory control might help in risk stratification for sudden cardiac death.

Key Words: baroreceptors • respiration • death, sudden    *

 (A16)

Diabetes Care 27:2701-2706, 2004

Glycemic Index and Dietary Fiber and the Risk of Type 2 Diabetes

Allison M. Hodge, MENVSC1 Dallas R. English, PhD Kerin O'Dea, PhD Graham G. Giles, PhD

OBJECTIVE- To examine associations between type 2 diabetes and fiber, glycemic load

(GL), dietary glycemic index (GI), and fiber-rich foods.

RESEARCH DESIGN AND METHODS- This was a prospective study of 36,787 men

and women aged 40-69 years without diabetes. For all self-reported cases of diabetes at 4-year

follow-up, confirmation of diagnosis was sought from medical practitioners. Case subjects were

those who reported diabetes at follow-up and for whom there was no evidence that they did not

have type 2 diabetes. Data were analyzed with logistic regression, adjusting for country of birth,

physical activity, family history of diabetes, alcohol and energy intake, education, 5-year weight

change, sex, and age.

RESULTS- Follow-up was completed by 31,641 (86%) participants, and 365 cases were

identified. The odds ratio (OR) for the highest quartile of white bread intake compared with the

lowest was 1.37 (95% CI 1.04 -1.81; P for trend_0.001). Intakes of carbohydrate (OR per 200

g/day 0.58, 0.36-0.95), sugars (OR per 100 g/day 0.61, 0.47- 0.79), and magnesium (OR per

500 mg/day 0.62, 0.43- 0.90) were inversely associated with incidence of diabetes, whereas

intake of starch (OR per 100 g/day 1.47, 1.06 -2.05) and dietary GI (OR per 10 units 1.32,

1.05-1.66) were positively associated with diabetes. These relationships were attenuated after

adjustment for BMI and waist-to-hip ratio.

CONCLUSIONS- Reducing dietary GI while maintaining a high carbohydrate intake may

reduce the risk of type 2 diabetes. One way to achieve this would be to substitute white bread

with low-GI breads.*

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Ann Intern Med. 2002 Apr 2;136(7):523-8.

 BRIEF COMMUNICATION Change in Coronary Flow Reserve on Transthoracic Doppler Echocardiography after a Single High-Fat Meal in Young Healthy Men

Takeshi Hozumi, MD; Marc Eisenberg, MD; Kenichi Sugioka, MD; Aravind R. Kokkirala, MD; Hiroyuki Watanabe, MD; Masakazu Teragaki, MD; Junichi Yoshikawa, MD; and Shunichi Homma, MD

2 April 2002 | Volume 136 Issue 7 | Pages 523-528

Background: High-fat meals and elevated triglyceride levels are associated with cardiovascular disease. In recent studies of brachial artery vasoactivity, a single high-fat meal reduced endothelial function in young healthy men. It is unknown whether coronary microcirculation is affected after high-fat meals.

Objective: To evaluate change in coronary flow reserve after a single high-fat meal.

Design: Controlled interventional study.

Setting: University hospitals.

Patients: 15 young healthy men (mean age [±SD], 29 ± 4 years).

Intervention: Coronary flow reserve was determined by using transthoracic Doppler echocardiography before and after consumption of a high-fat meal in all 15 men and before and after consumption of a low-fat meal in 5 of 15 men.

Measurements: Coronary flow reserve, lipid levels, and hemodynamic characteristics.

Results: In all men, triglyceride levels increased significantly from baseline 5 hours after the high-fat meal, from 1.1 mmol/L to 2.8 mmol/L (100 mg/dL to 250 mg/dL) (P < 0.001). Average coronary flow reserve was 4.02 before and 3.30 5 hours after the high-fat meal (decrease, 18% [95% CI, 13% to 23%]). In the 5 men who received both meals, mean coronary flow reserve decreased by 0.79 after the high-fat meal and increased by 0.07 after the low-fat meal (difference, -0.86 [CI, -1.36 to -0.37]; P = 0.03). Mean triglyceride levels increased by 1.6 mmol/L (140 mg/dL) after the high-fat meal and 0.1 mmol/L (10 mg/dL) after the low-fat meal (difference, 1.5 mmol/L [CI, 0.3 to 2.7 mmol/L], 130 mg/dL [CI, 23 to 236 mg/dL]; P = 0.03).

Conclusions: Coronary flow reserve decreased after a single high-fat meal in young healthy men. High-fat meals may be detrimental to coronary microcirculation.     *

 (A18)

Circulation. 2001;103:2424.)

(c) 2001 American Heart Association, Inc.

Brief Rapid Communications

Does Reduced Vascular Stiffening Fully Explain Preserved Cardiovagal Baroreflex Function in Older, Physically Active Men?

Brian E. Hunt, PhD; William B. Farquhar, PhD; J. Andrew Taylor, PhD

From the Laboratory for Cardiovascular Research, Research and Training Institute, Hebrew Rehabilitation Center for Aged, and the Division on Aging, Harvard Medical School, Boston, Mass.

Correspondence to Brian E. Hunt, PhD, Laboratory for Cardiovascular Research, Research and Training Institute, Hebrew Center for Aged, 1200 Centre St, Boston, MA 02131. E-mail hunt@mail.hrca.harvard.edu

Background-We measured cardiovagal baroreflex gain and its vascular mechanical and neural components during dynamic baroreflex engagement in 10 young untrained men, 6 older untrained men, and 12 older, physically active men.

Methods and Results-Our newly developed assessment of beat-to-beat carotid diameters during baroreflex engagement estimates the mechanical transduction of pressure into barosensory stretch (diameter/pressure), the neural transduction of stretch into vagal outflow (R-R interval/diameter), and conventional integrated cardiovagal baroreflex gain (R-R interval/pressure). Integrated gain was lower in older untrained men than in young untrained men (6.8±1.2 versus 15.7±1.8 ms/mm Hg) due to both lower mechanical (9.1±1.0 versus 17.1±2.4 mm Hg/µm) and lower neural (0.57±0.10 versus 0.90±0.10 ms/µm) transduction. Integrated gain in older active men (13.3±2.7 ms/mm Hg) was comparable to that in young untrained men. This was achieved through mechanical transduction (12.1±1.4 mm Hg/µm) that was modestly higher than that in older untrained men and neural transduction (1.00±0.20 ms/µm) comparable to that in young untrained men. Across groups, both mechanical and neural components were related to integrated gain; however, the neural component carried greater predictive weight (ß=0.789 versus 0.588).

Conclusions-Both vascular and neural deficits contribute to age-related declines in cardiovagal baroreflex gain; however, long-term physical activity attenuates this decline by maintaining neural vagal control.     *

 (A19)

Am J Hypertens 2003 Aug;16(8):629-33 (ISSN: 0895-7061)

How much exercise is required to reduce blood pressure in essential hypertensives: a dose-response study.

Ishikawa-Takata K; Ohta T; Tanaka H

Division of Health Promotion and Exercise (KI-T), National Institute of Health and Nutrition, 1-23-1 Toyama Shinjyuku, Tokyo 162-8636, Japan. kazu@nih.go.jp.

BACKGROUND: Regular aerobic exercise is widely recommended for essential hypertensives. However, it is not clear how much exercise is needed to reduce blood pressure (BP). METHODS: The dose-response relation of exercise training and BP was determined using an 8-week exercise intervention study involving 207 untreated subjects with stage 1 or 2 essential hypertension. Subjects were divided into five groups based on the duration and frequency/week of exercise (sedentary control, 30 to 60 min/wk, 61 to 90 min/wk, 91 to 120 min/wk, and >120 min/wk). Age, gender, height, body mass, body mass index, dietary intake, and baseline BP were not different among the groups. RESULTS: Both systolic and diastolic BP at rest did not change in the nonexercising control group. All four exercise groups demonstrated significant reductions in both systolic and diastolic BP at rest. The magnitude of reductions in systolic BP was greater in the 61 to 90 min/wk group compared with the 30 to 60 min/wk group. There were no greater reductions in systolic BP with further increases in exercise volume. The magnitude of reductions in diastolic BP was not significantly different among four exercise groups. There were no obvious relations between exercise frequency per week and the magnitude of BP decreases with exercise training. CONCLUSIONS: In previously sedentary hypertensive subjects, clinically significant decreases in BP can be achieved with relatively modest increases in physical activity above sedentary levels and that the volume of exercise required to reduce BP may be relatively small that should be reasonably attainable by a sedentary hypertensive population.     *

 (A20)

PNAS | July 22, 2003 | vol. 100 | no. 15 | 9090-9095 Psychology

Chronic stress and age-related increases in the proinflammatory cytokine IL-6

Janice K. Kiecolt-Glaser * , Kristopher J. Preacher , Robert C. MacCallum ¶, Cathie Atkinson *, William B. Malarkey  || and Ronald Glaser   ** 

Departments of *Psychiatry, ||Internal Medicine, and **Molecular Virology, Immunology, and Medical Genetics, Ohio State University College of Medicine, Columbus, OH 43210; Department of Psychology, Institute for Behavioral Medicine Research, and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210; and ¶Department of Psychology, University of North Carolina, Chapel Hill, NC 27599

Edited by Burton H. Singer, Princeton University, Princeton, NJ and approved June 3, 2003 (received for review April 2, 2003)

To whom correspondence should be addressed. E-mail: glaser.1@osu.edu.

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Abbreviations: CRP, C-reactive protein; BMI, body mass index. *

 (A21)

New England J Medicine Volume 346:393-403  February 7, 2002  Number 6

Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or MetforminDiabetes Prevention Program Research Group

The writing group (William C. Knowler,) M.D., Dr.P.H., Elizabeth Barrett-Connor, M.D., Sarah E. Fowler, Ph.D., Richard F. Hamman, M.D., Dr.P.H., John M. Lachin, Sc.D., Elizabeth A. Walker, D.N.Sc., and David M. Nathan, M.D.) takes responsibility for the content of this article.

Address reprint requests to the Diabetes Prevention Program Coordinating Center, Biostatistics Center, George Washington University, 6110 Executive Blvd., Suite 750, Rockville, MD 20852.

ABSTRACT

Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors - elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle - are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups.

Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin.

Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin. *

 (A22)

Lancet 1998; 351: 4, 78-84

Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction

Maria Teresa La Rovere, J Thomas Bigger Jr, Frank I Marcus, Andrea Mortara, Peter J Schwartz, for the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators

Centro Medico Montescano, Fondazione "Salvatore Maugeri", Montescano, Pavia, Italy (M T La Rovere MD, A Mortara MD); Columbia University College of Physicians and Surgeons, Department of Medicine, Cardiology Division, New York, NY (Prof J T Bigger Jr MD); University of Arizona Health Sciences Center, Department of Internal Medicine, Section of Cardiology, Tucson, AZ, USA (Prof F I Marcus MD); and Department of Cardiology, University of Pavia and Policlinico S Matteo IRCCS, Pavia, Italy (Prof P J Schwartz MD)

Correspondence to: Dr Maria Teresa La Rovere, Centro Medico Montescano, Fondazione "Salvatore Maugeri", Via per Montescano, 27040 Montescano (PV), Italy

Summary

BackgroundExperimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity (BRS) may contribute to post-infarction risk stratification. There are clinical data to support this concept for heart-rate variability. The main objective of the ATRAMI study was to provide prospective data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infarction in whom left-ventricular ejection fraction (LVEF) and ventricular arrhythmias were known.

Methods This multicentre international prospective study enrolled 1284 patients with a recent (<28 days) myocardial infarction. 24 h Holter recording was done to quantify heart-rate variability (measured as standard deviation of normal to normal RR intervals [SDNN]) and ventricular arrhythmias. BRS was calculated from measurement of the rate-pressure response to intravenous phenylephrine.

Findings During 21 (SD 8) months of follow-up, the primary endpoint, cardiac mortality, included 44 cardiac deaths and five non-fatal cardiac arrests. Low values of either heart-rate variability (SDNN <70 ms) or BRS (<3·0 ms per mm Hg) carried a significant multivariate risk of cardiac mortality (3·2 [95% CI 1·42-7·36] and 2·8 [1·24-6·16], respectively). The association of low SDNN and BRS further increased risk; the 2-year mortality was 17% when both were below the cut-offs and 2% (p<0·0001) when both were well preserved (SDNN >105 ms, BRS >6·1 ms per mm Hg). The association of low SDNN or BRS with LVEF below 35% carried a relative risk of 6·7 (3·1-14·6) or 8·7 (4·3-17·6), respectively, compared with patients with LVEF above 35% and less compromised SDNN (70 ms) and BRS (3 ms per mm Hg).

Interpretation ATRAMI provides clinical evidence that after myocardial infarction the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability.*

 (A23)

Note added by Phil Harris. Reference 9 appears not to be available in Abstract. Relaxation techniques were an important part of therapy in this programme. A Yoga expert helped train patients in the early pilot study.

Heart 1999;82:654-655 ( December )

Improving quality of life in patients with angina

R J P Lewin

British Heart Foundation Rehabilitation Research Unit, Department of Health Studies, The University of York, Genesis 6, York Science Park, Heslington, York YO10 5DG, UK, emailrjpl1@york.ac.uk

Editorial

Angina appears to have a particularly deleterious effect on a patient's quality of life. In a community survey in which the short form 36 (SF36) was administered to 1200 patients with 11 different chronic illnesses (including arthritis, sciatica, back pain, diabetes, depression, and stroke) only patients suffering from chronic anxiety reported a more severe detrimental effect on their general health.1 These patients were already receiving medical treatment, what more could have been done to help them?

Interventional treatments

Both coronary artery bypass grafting and angioplasty provide worthwhile reductions in symptoms and reduce early mortality in selected patients. The relative merits of each procedure are likely to be debated for some time but, whatever the final consensus, without a huge increase in resources, neither intervention will help most angina patients. In the UK there are approximately 1.6 million people with angina,2 of whom approximately 20% are referred to secondary care3 and 2% receive surgery or angioplasty each year.2 The long waiting lists for referral to secondary care, the scarcity of cardiologists, and an aging population make it likely that, for some time to come, the vast majority of patients with angina will remain unknown to secondary care and will not be considered for surgery or angioplasty.

Care in the community

Two recent community based studies have demonstrated that improved care can produce significant improvements in both clinical status and quality of life. In the first of these studies 688 primary care patients with angina were randomised to health education delivered by health visitors, or to routine medical care. The study produced improvements in the educational group in: activity levels, compliance with medication, lifestyle, and quality of life.4 In the second study, 1173 patients, of whom 50% had angina, were recruited from 19 general practices in Aberdeenshire.5 Practice nurses worked to a specially designed treatment manual to review medical treatment and negotiate behaviour change with patients. Intervention patients had significant improvement in blood pressure, lipids, and aspirin use, a 28% reduction in hospital admissions, and an improvement in quality of life.5 Both of these interventions were largely educational, neither included a formal exercise component or psychological interventions, two of the main components of cardiac rehabilitation. Meta-analyses and systematic review suggest that, in myocardial infarction patients, rehabilitation improves quality of life and reduces cardiac and all cause mortality by 20-25%.6 Could cardiac rehabilitation provide similar gains for angina patients?

Cardiac rehabilitation

Trials of cardiac rehabilitation programmes specifically designed for angina patients have shown considerable promise. For example, an exercise trial that crossed over patients from blockade to exercise, showed the antianginal benefits of exercise to be equal to that of  blockade.7 In the lifestyle trial, a rehabilitation programme in which the main elements were exercise, stress management, and a low fat diet, the intervention patients reported a 90% reduction in angina at one year and 82% showed some degree of regression of coronary artery disease.8 In a trial of a specially developed angina management programme conducted by our group, patients reported a 70% reduction in episodes of angina and a 72% improvement in quality of life at one year. Of those awaiting elective bypass surgery on entry to the programme 50% were subsequently removed from the waiting list after independent review by their cardiologist9 and the vast majority of these patients have not required any further cardiological intervention 3-7 years after treatment.

The latter trials were distinguished by their addition of psychological treatments, such as stress management and relaxation therapy, to exercise. There have also been a number of purely psychological interventions for angina, these have been reviewed elsewhere.10 The two treatments that showed the most promise were relaxation therapy and stress management.10 It appears that rehabilitation might provide substantial gains for patients. Unfortunately, cardiac rehabilitation programmes in the UK are underprovided, underresourced, and poorly supported by medicine.11 They usually only enrol postmyocardial infarction or cardiac surgery patients referred from secondary care, and currently treat fewer than 50% of these patients. Angina and heart failure are often used to exclude patients from cardiac rehabilitation, this is ironic as they are two groups who particularly benefit from an increased exercise capacity. There is a clear rationale for exercise training but what benefits can psychological treatments provide?

Psychological factors in the production of angina

Psychological factors have been associated with angina since its description. Herberden named it after the choking sensation of fear that accompanied each attack. John Hunter described how an 18th century surgeon's everyday worriesfor example, that his bees might have swarmed while he was up in town, could provoke angina, and modern Holter monitoring studies confirm that as many as 50% of ischaemic episodes may be triggered by emotion rather than exertion.12 It is possible that this is through an interaction between raised autonomic drive and vasoconstriction. A number of other dynamic factors such as decreased myocardial contractility, increased afterload and alkalosis due to emotionally induced hyperventilation may also be involved.10 In a number of studies, questionnaire measures of anxiety, depression, and neuroticism have all shown moderate, positive correlations with the frequency and severity of the self report of angina, independent of the extent of coronary artery disease,11 which in itself is not predictive of self reported angina or disability. The success of medical treatment is also linked to psychological factors; at Duke University Medical Centre, Williams et al were able to predict prospectively 85% of patients who would succeed on medical treatment and 61% of those who would not, using an empirically derived model, the main element of which was the score on a questionnaire measure of hypochondriasis.13 The authors noted that it is these patients, who are not different on any measurable cardiological feature, who constitute the bulk of those referred on from primary care to cardiology for further investigations due to insufficient symptom relief from medical treatment.

What is so bad about angina?

This may appear a somewhat redundant and insensitive question, the obvious answer being "the pain and discomfort it causes", but this does not accord with the data. In the community survey of quality of life,1 the angina patient's pain score was less than half that of patients with sciatica, arthritis, and back pain, and roughly similar to patients with chronic anxiety states. Yet, although objectively the prognosis for the average stroke patient is far worse than that for an angina patient, the angina patients scored their general health as being twice as poor as did patients with stroke1 and lower than all other patients except those with chronic anxiety. Angina appears to have a disproportionately severe impact on a patient's view of their health status. With the development of sophisticated imaging techniques "angor animi" may no longer be regarded as a strong diagnostic sign of angina pectoris, but there is no reason to believe that the acute anxiety and the fear of death that accompanies angina is any less real or has any less impact on quality of life, than it did in 1772.

In the past few years it has become increasingly clear that such beliefs and attributions are important predictors of outcome. For example, in a study of 400 patients who failed to return to work following uncomplicated myocardial infarction, Wynn claimed that in 40% of cases the reason could be directly attributed to an immanent fear of death due to an overcautious prognosis.14 In a further 23% of cases the patients' anxiety was directly related to a cardiac misconception such as, "every attack of angina causes further damage to my heart".14 In several surveys it has been shown that 80% of patients believe that the primary cause of their heart disease was worry or stress or overwork. In the face of such beliefs the most obvious coping strategy is to rest and to avoid the demands, stresses, and excitements and thus often the rewards, of a normal life.15 Unfortunately, many health professionals share these misconceptions and reinforce them, urging patients to avoid provoking angina, to rest and to "take things easy". Most physicians are now aware that rest is an inappropriate prescription for back pain, and angina may be the only remaining medical condition for which rest is (often unintentionally) prescribed.

Our experience in developing and evaluating the angina management programme is that it is important to educate patients about the true causes of angina, to reduce their exaggerated health worries, and to give them hope that through lifestyle changes they can fight back against premature death. It is important to provide specific advice and guidance about the lifestyle changes required and to encourage them to return to as normal a life as possible. Most of our patients have had a number of years of living with angina, usually becoming increasingly disabled by it. It seems possible to many of them and reasonable to us, that if better advice and guidance were given to patients close to the time of diagnosis, fewer of them would lapse into the fearful and restricted lifestyle that leads to reduced quality of life. We are currently evaluating this possibility in a controlled trial of a very brief educational intervention suitable for use in primary or secondary care shortly after diagnosis.

Conclusion

There is much that could be done to improve quality of life for the average angina patient. Improved cardiac education and hospital based rehabilitation programmes have both demonstrated worthwhile benefits. To cope with the numbers involved new community based rehabilitation programmes should be developed for patients with chronic stable angina. It has been shown that self help rehabilitation programmes can be delivered by specially trained practice nurses or health visitors, working from manuals,5 16 and this may be a practical and cost effective approach. Patients with more complex problems or those who do not respond to simple community based rehabilitation methods should be referred to more intensive rehabilitation programmes in secondary care. These programmes require greater investment in staff training and resources. Patients' beliefs about heart disease are often the most important determinant of their disability and quality of life. These factors should be addressed by medical staff at the point of diagnosis and throughout the illness career. It is important to emphasise that death is not imminent, that many risk factors are controllable by the patient and doctor, with very worthwhile clinical benefits, and that there is no evidence that brief periods of ischaemia are damaging. The common misconceptions that lead to undue anxiety and to the abandoning of enjoyable activitiesfor example, that each episode is a mini-heart attack, or that the cure is to rest, should be sought out and changed in the patient and wherever possible their family. A programme of daily walking, starting within the patients' current ability and being stepped up within the patients' comfort zone as their fitness increases, is simple to organise and to monitor. Above all clinicians should try to imbue patients with a sense of optimism and control over their fate by encouraging an active participation in the management of the condition.

Acknowledgments

Although I take full responsibility for any inaccuracies or opinions I would like to thank Professor Brian Pentecost, Professor Keith Fox, and Dr Iain Todd for their helpful comments and suggestions on earlier drafts of this manuscript.

References

1.  Lyons RA, Lo SV, Littlepage BNC. Comparative health status of patients with 11 common illnesses in Wales. J Epidemiol Community Health 1994;48:388-390

2.  British Heart Foundation Health Promotion Research Group. Coronary heart disease statistics. London: British Heart Foundation, 1998. 

3.  Ghandi MM, Lampe C, Wood DA. Incidence, clinical characteristics, and short-term prognosis of angina pectoris. Br Heart J 1995;73:193-198

4.  Cupples ME, McKnight A. Randomised controlled trial of health promotion in general practice for patients at high cardiovascular risk. BMJ 1995;309:993-996

5.  Campbell NC, Thain J, Deans HG, et al. Secondary prevention clinics for coronary heart disease: randomised trial of effect on health. BMJ 1998;316:1434-1437

6.  NHS Centre for Reviews and Dissemination. Effective health carecardiac rehabilitation, volume 4, number 4. York: University of York, 1998. 

7.  Todd IC, Ballantyne D. Antianginal efficacy of exercise training: a comparison with  blockade. Br Heart J 1990;64:14-19

8.  Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? Lancet 1990;336:129-133

9.  Lewin B, Cay EL, Todd I, et al. The angina management programme: a rehabilitation treatment. Br J Cardiol 1995;1:221-226. 

10.  Lewin B. The psychological and behavioural management of angina. J Psychosom Res 1997;5:452-462. 

11.  Lewin RJ, Ingleton R, Newens AJ, et al. Adherence to cardiac rehabilitaion guidelines: a survey of cardiac rehabilitation programmes in the United Kingdom. BMJ 1998;316:1354-1355

12.  Deanfield JE, Maseri A, Selwyn AP, et al. Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes. Lancet 1983;ii:753-758. 

13.  Williams RB, Haney TL, McKinnis RA, et al. Psychosocial and physical predictors of anginal pain relief with medical management. Psychosom Med 1986;48:200-210

14.  Wynn A. Unwarranted emotional distress in men with ischaemic heart disease. Med J Aust 1967;2:847-851[Medline]. 

15.  Fielding R. Patients' beliefs regarding the causes of myocardial infarction: implications for information-giving and compliance. Patient Education and Counselling 1987;9:121-134. 

16.    Lewin B, Robertson IH, Cay EL, et al. Effects of a self-help post-myocardial-infarction rehabilitation on psychological adjustment and use of health services. Lancet 1992;339:1036-1040*

 (A24)

J Am Soc Nephrol 14:S108-S113, 2003

(c) 2003 American Society of Nephrology

Supplement Article

Prevention of Diabetes Mellitus in Subjects with Impaired Glucose Tolerance in the Finnish Diabetes Prevention Study: Results From a Randomized Clinical Trial

Jaana Lindström*, Johan G. Eriksson*, Timo T. Valle*, Sirkka Aunola, Zygimantas Cepaitis*, Martti Hakumäki, Helena Hämäläinen, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi¶, Mauri Laakso**, Anne Louheranta, Marjo Mannelin**, Vesa Martikkala*, Vladislav Moltchanov**, Merja Rastas, Virpi Salminen,, Jouko Sundvall, Matti Uusitupaand Jaakko Tuomilehto*,

*National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, Helsinki; Social Insurance Institution, Research Department, Turku; University of Kuopio, Department of Clinical Nutrition, Kuopio; Finnish Diabetes Association, The Diabetes Centre, Tampere; ¶University of Oulu, Department of Public Health Science and General Practice, Oulu; **Oulu Deaconess Institute, Department of Sports Medicine, Oulu; Institute of Nursing and Health Care, Tampere; National Public Health Institute, Department of Health and Functional Capacity, Helsinki; and University of Helsinki, Department of Public Health, Helsinki, Finland.

Correspondence to Jaakko Tuomilehto, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. Phone: 358-9-4744-8635; Fax: 358-9-4744-8338;

ABSTRACT. Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle. The Finnish Diabetes Prevention Study (DPS) is the first individually randomized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects. We randomly assigned 522 (172 men, 350 women) middle-aged (mean age 55 yr), overweight (mean body mass index 31 kg/m2) subjects with impaired glucose tolerance either to the lifestyle intervention or control group. Each subject in the intervention group received individualized counseling aimed at reducing weight and intake of total and saturated fat, and increasing intake of fiber and physical activity. An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters. The mean (± SD) weight reduction from baseline to year 1 and to year 2, respectively, was 4.2 ± 5.1 kg and 3.5 ± 5.5 in the intervention group and 0.8 ± 3.7kg and 0.8 ±4.4 im the control group (P<0.001 between the groups). At the time of the first analysis of the outcome data the mean duration of follow-up was 3.2 yr. the risk of diabetes was reduced by 58% (P<0.001) in the intervension group compared with the control group. The reduction in the incidence of diabetes was directly associated with the number and magnitude of lifestyle changes made. In conclusion, the DPS is the first controlled trial demonstrating that type two diabetes can be prevented by changes in lifestyle in high-risk subjects *

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