Sudhir Kurl

Metabolic Syndrome and the Risk of Stroke in Middle-Aged Men

Background and Purpose— The metabolic syndrome, a clustering of disturbed glucose and insulin metabolism, obesity and abdominal fat distribution, dyslipidemia, and hypertension is associated with cardiovascular diseases. The aim of this study was to examine the relationship of metabolic syndrome, as defined by National Cholesterol Education Program (NCEP) and World Health Organization (WHO) criteria, with the risk for stroke. Methods— Population-based cohort study with an average follow-up of 14.3 years from eastern Finland. A total of 1131 men with no history of cardiovascular disease and diabetes at baseline participated. Sixty-five strokes occurred, of which 47 were ischemic strokes. Results— Men with the metabolic syndrome as defined by the NCEP criteria had a 2.05-fold (95% CI, 1.03 to 4.11; P=0.042) risk for all strokes and 2.41-fold (95% CI, 1.12 to 5.32; P=0.025) risk for ischemic stroke, after adjusting for socioeconomic status, smoking, alcohol, and family history of coronary heart disease. Additional adjustment for ischemic changes during exercise test, serum low-density lipoprotein cholesterol, plasma fibrinogen, energy intake for saturated fats, energy expenditure of leisure time physical activity, and white blood cell count, the results remained significant. The risk ratios among men with metabolic syndrome as defined by the WHO criteria were 1.82 (95% CI, 1.01 to 3.26; P=0.046) for all strokes and 2.16 (95% CI, 1.11 to 4.19; P=0.022) for ischemic stroke. After further adjustment, the respective risks were 2.08 (95% CI, 1.12 to 3.87; P=0.020) and 2.47 (95% CI, 1.21 to 5.07; P=0.013). Conclusion— The risk of any stroke is increased in men with metabolic syndrome, in the absence of stroke, diabetes and cardiovascular disease at baseline. Prevention of the metabolic syndrome presents a great challenge for clinicians with respect to stroke.

Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study

The role of flavonoids in CVD, especially in strokes, is unclear. Our aim was to study the role of flavonoids in CVD. We studied the association between the intakes of five subclasses (flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins), a total of twenty-six flavonoids, on the risk of ischaemic stroke and CVD mortality. The study population consisted of 1950 eastern Finnish men aged 42-60 years free of prior CHD or stroke as part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up time of 15.2 years, 102 ischaemic strokes and 153 CVD deaths occurred. In the Cox proportional hazards model adjusted for age and examination years, BMI,systolic blood pressure, hypertension medication, serum HDL- and LDL-cholesterol, serum TAG, maximal oxygen uptake, smoking, family history of CVD, diabetes, alcohol intake, energy-adjusted intake of folate, vitamin E, total fat and saturated fat intake (percentage of energy), men in the highest quartile of flavonol and flavan-3-ol intakes had a relative risk of 0.55 (95% CI 0.31, 0.99) and 0.59 (95% CI 0.30, 1.14) for ischaemic stroke, respectively, as compared with the lowest quartile. After multivariate adjustment, the relative risk for CVD death in the highest quartile of flavanone and flavone intakes were 0.54 (95% CI 0.32, 0.92) and 0.65 (95% CI 0.40, 1.05), respectively. The present results suggest that high intakes of flavonoids may be associated with decreased risk of ischaemic stroke and possibly with reduced CVD mortality.

Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: results of the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study.

OBJECTIVES The goal of this study was to compare the performance of several measures of carotid intima-media thickness (C-IMT) as predictors of cardiovascular events (CVEs), and to investigate whether they add to the predictive accuracy of Framingham risk factors (FRFs). BACKGROUND Various markers of subclinical atherosclerosis have been identified as predictors of CVEs, but the most powerful variable is still under debate. METHODS A cohort study was carried out in 5 European countries. A total of 3,703 subjects (median age 64.4 years; 48% men) were followed-up for a median of 36.2 months, and 215 suffered a first CVE (incidence: 19.9/1,000 person-years). RESULTS All measures of C-IMT and the interadventitia common carotid artery diameter (ICCAD) were associated with the risk of CVEs, after adjustment for FRFs and therapies (all p < 0.005). The average of 8 maximal IMT measurements (IMT(mean-max)), alone or combined with ICCAD, classified events and non-events better than the common carotid mean IMT (net reclassification improvement [NRI]: +11.6% and +19.9%, respectively; both p < 0.01). Compared with classification based on FRFs alone, the NRI resulting from the combination of FRFs+ICCAD+IMT(mean-max) was +12.1% (p < 0.01). The presence of at least 1 plaque (maximum IMT >1.5 mm) performed significantly worse than composite IMTs that incorporated plaques (p < 0.001). Adjusted Kaplan-Meier curves showed that individuals with a FRS = 22.6% (cohort average), and both IMT(mean-max) and ICCAD above the median, had a 6.5% risk to develop a CVE over 3 years versus a 3.4% risk for those with the same FRS, and both IMT(mean-max) and ICCAD below the median. CONCLUSIONS A risk stratification strategy based on C-IMT and ICCAD as an adjunct to FRFs is a rational approach to prevention of cardiovascular disease.

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in Middle-aged men

OBJECTIVES We investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD). BACKGROUND Silent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD. METHODS We investigated the association of silent ischemia, as defined by ST depression during and after maximal symptom-limited exercise test, with coronary risk in a population-based sample of men with no prior CHD followed for 10 years on average. RESULTS Silent ischemia during exercise was associated with a 5.9-fold (95% CI 2.3 to 11.8) CHD mortality in smokers, 3.8-fold (95% CI 1.9 to 7.9) in hypercholesterolemic men and 4.7-fold (95% CI 2.4 to 9.1) in hypertensive men adjusting for other risk factors. The respective relative risks (RRs) of any acute coronary event were 3.0 (95% CI 1.7 to 5.1), 1.9 (95% CI 1.2 to 3.1) and 2.2 (95% CI 1.4 to 3.5). These associations were weaker in men without these risk factors. Furthermore, silent ischemia after exercise was a stronger predictor for the risk of acute coronary events and CHD death in smokers and in hypercholesterolemic and hypertensive men than in men without risk factors. CONCLUSIONS Exercise-induced silent myocardial ischemia was a strong predictor of CHD in men with any conventional risk factor, emphasizing the importance of exercise testing to identify asymptomatic high risk men who could benefit from risk reduction and preventive measures.

Cardiorespiratory Fitness Is Related to the Risk of Sudden Cardiac Death : A Population-Based Follow-Up Study

OBJECTIVES Our aim was to examine the relation of cardiorespiratory fitness with sudden cardiac death (SCD) in a population-based sample of men. BACKGROUND Very limited information is available about the role of cardiorespiratory fitness in the prediction of SCD. METHODS This population study was based on 2,368 men 42 to 60 years of age. Cardiorespiratory fitness was defined by using respiratory gas exchange analyzer and maximal workload during cycle ergometer exercise test. RESULTS During the 17-year follow-up, there were 146 SCDs. As a continuous variable, 1 metabolic equivalent (MET) increment in cardiorespiratory fitness was related to a decrease of 22% in the risk of SCD (relative risk: 0.78, 95% confidence interval: 0.71 to 0.84, p<0.001). In addition to cardiorespiratory fitness, ischemic ST-segment depression during exercise testing, smoking, systolic blood pressure, prevalent coronary heart disease, family history of coronary heart disease, and type 2 diabetes mellitus were related to the risk of SCD. The Harrell C-index for the total model discrimination was 0.767, while cardiorespiratory fitness provides modest improvement (from 0.760 to 0.767) in the risk prediction when added with all other risk factors. The integrated discrimination improvement was 0.0087 (p=0.018, relative integrated discrimination improvement 0.11) when cardiorespiratory fitness was added in the model. However, the net reclassification index (-0.018) was not statistically significantly improved (p=0.703). CONCLUSIONS Cardiorespiratory fitness is a predictor of SCD in addition to that predicted by conventional risk factors. There was a slight improvement in the level of discrimination, although the net reclassification index did not change while using cardiorespiratory fitness with conventional risk factors.

Plasma Vitamin C Modifies the Association Between Hypertension and Risk of Stroke

Background and Purpose— There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland. Methods— We conducted a 10.4-year prospective population-based cohort study of 2419 randomly selected middle-aged men (42 to 60 years) with no history of stroke at baseline examination. A total of 120 men developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes. Results— Men with the lowest levels of plasma vitamin C (<28.4 &mgr;mol/L, lowest quarter) had a 2.4-fold (95% CI, 1.4 to 4.3;P =0.002) risk of any stroke compared with men with highest levels of plasma vitamin C (>64.96 &mgr;mol/L, highest quarter) after adjustment for age and examination months. An additional adjustment for body mass index, systolic blood pressure, smoking, alcohol consumption, serum total cholesterol, diabetes, and exercise-induced myocardial ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2 to 3.8;P =0.01). Adjustment for prevalent coronary heart disease and atrial fibrillation did not attenuate the association any further. Furthermore, hypertensive men with the lowest vitamin C levels (<28.4 &mgr;mol/L) had a 2.6-fold risk (95% CI, 1.52 to 4.48;P <0.001), and overweight men (≥25 kg/m2) with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90;P =0.001) for any stroke after adjustment for age, examination months, and other risk factors. Conclusions— Low plasma vitamin C was associated with increased risk of stroke, especially among hypertensive and overweight men.

Systolic Blood Pressure During Recovery From Exercise and the Risk of Acute Myocardial Infarction in Middle-Aged Men

We prospectively assessed the association of systolic blood pressure (SBP) after exercise with the risk of an acute myocardial infarction. Limited information exists currently on the role of SBP during recovery period with the risk of acute myocardial infarction. SBP was measured every 2 minutes during and after a progressive cycle ergometer exercise test in a representative sample of 2336 men (aged 42 to 61 years). During an average follow-up period of 13.1 years, 358 acute myocardial infarctions occurred. An incremental rise of 10 mm Hg per minute in SBP at 2 minutes after exercise (relative risk, 1.07-fold; 95% confidence interval [CI], 1.03 to 1.12; P=0.001) was associated with the risk of acute myocardial infarction after adjustment for age, alcohol consumption, smoking, serum lipids, diabetes mellitus, body mass index, resting SBP, regular use of antihypertensive medications, physical fitness, heart rate, and ischemic ECG findings during exercise. Men with elevated SBP of >195 mm Hg after exercise had a 1.69-fold (95% CI, 1.24 to 2.30; P=0.001) risk for an acute myocardial infarction compared with those with SBP <170 mm Hg after adjustment for age, other risk factors, and resting SBP. SBP after exercise provides an incremental predictive value for acute myocardial infarction beyond that of resting SBP. This emphasizes the importance of SBP measurements after the exercise test because it provides additional valuable prognostic measure with regard to acute myocardial infarction.

Duration of QRS Complex in Resting Electrocardiogram Is a Predictor of Sudden Cardiac Death in Men

Background— Previous studies indicate that increased QRS duration in ECG is related to the risk of all-cause death. However, the association of QRS duration with the risk of sudden cardiac death (SCD) is not well documented in large population-based studies. Our aim was to examine the relation of QRS duration with SCD in a population-based sample of men. Methods and Results— This prospective study was based on a cohort of 2049 men aged 42 to 60 years at baseline with a 19-year follow-up, during which a total of 156 SCDs occurred. As a continuous variable, each 10-ms increase in QRS duration was associated with a 27% higher risk for SCD (relative risk, 1.27; 95% confidence interval, 1.14–1.40; P<0.001). Subjects with QRS duration of >110 ms (highest quintile) had a 2.50-fold risk for SCD (relative risk, 2.50; 95% confidence interval, 1.38–4.55; P=0.002) compared with those with QRS duration of <96 ms (lowest quintile), after adjustment for established key demographic and clinical risk factors (age, alcohol consumption, previous myocardial infarction, smoking, serum low- and high-density lipoprotein cholesterol, C-reactive protein, type 2 diabetes mellitus, body mass index, systolic blood pressure, and cardiorespiratory fitness). In addition to QRS duration, smoking, previous myocardial infarction, type 2 diabetes mellitus, cardiorespiratory fitness, body mass index, systolic blood pressure, and C-reactive protein were independently associated with the risk of SCD. Conclusions— QRS duration is an independent predictor of the risk of SCD and may have utility in estimating SCD risk in the general population.

Determinants of cardiorespiratory fitness in men aged 42 to 60 years with and without cardiovascular disease.

Good cardiorespiratory fitness has been found to protect against cardiovascular diseases and type 2 diabetes. The purpose of this study was to investigate determinants of directly measured cardiorespiratory fitness (maximal oxygen uptake [VO2max]), including age, body composition, prevalent diseases, cardiovascular and pulmonary functions, biochemical factors, physical activity, nutrition, smoking, and alcohol consumption, in a population-based study of 936 men 42 to 60 years of age. Variables that had the strongest direct associations with VO2max (milliliters per minute) in a linear multivariate step-up regression model were body weight, heart rate at maximal exercise, mean intensity and frequency of conditioning physical activity, intake of carbohydrates, blood hemoglobin, and forced expiratory volume in 1 second. The strongest inverse associations with VO2max were heart rate at rest, age, fasting serum insulin, waist-to-hip ratio, coronary heart disease, and asthma. This model accounted for 67% of the variation of VO2max. In conclusion, mean intensity, frequency, and duration of conditioning physical activity were associated directly with VO2max. However, measurements of the function of pulmonary and cardiovascular systems, carbohydrate intake, and body composition were powerful determinants of cardiorespiratory fitness, especially in older middle-aged men.

Systolic blood pressure response to exercise testing is related to the risk of acute myocardial infarction in middle-aged men

Background We assessed the association of systolic blood pressure response to exercise with the risk of an acute myocardial infarction. Design We conducted a population-based follow-up study. Methods This study was based on 1731 middle-aged men without history of coronary heart disease who underwent a cycle ergometer exercise test. Systolic blood pressure was measured every 2 min during a cycle ergometer exercise test in 1731 men followed for 12.7 years on average. A total of 188 acute myocardial infarctions were observed. Results The total change in systolic blood pressure, the slope of the rise in systolic blood pressure per minute and maximal systolic blood pressure during exercise in quintiles were related to the risk of acute myocardial infarction. Maximal systolic blood pressure of over 230 mmHg was associated with a 2.47 [95% confidence interval (CI) 1.46-4.18] fold risk of acute myocardial infarction, after adjustment for age, other risk factors including the use of antihypertensive medications and systolic blood pressure at rest. Among men with elevated systolic blood pressure at rest, the relative risk for an acute myocardial infarction was 4.31 (95% CI 2.04-9.07) times higher for those who had a steep slope of systolic blood pressure rise (>9.4 mmHg per min of exercise) as compared with those who had a more gradual rise in systolic blood pressure. Conclusions Both rate and levels of rise in systolic blood pressure during a progressive exercise test were risk predictors for acute myocardial infarction. These measurements provide an incremental predictive value for an acute myocardial infarction to elevated resting systolic blood pressure, emphasizing the importance of regular blood pressure measurements during exercise testing. Eur J Cardiovasc Prev Rehabil 13:421-428