Showing papers by "Charles H. Hennekens published in 2000"

C-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in Women

Abstract: Background Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events. Methods We conducted a prospective, nested case–control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (slCAM-1). We also studied homocysteine and several lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronay-revascularization procedures. Results Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), slCAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), low-density lipoprotein (LDL) cholesterol (2.4), apolipoprotein B-100 (3.4), high-density lipoprotein (HDL) cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9). Conclusions The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying women at risk for cardiovascular events.

Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men

Abstract: Background—Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse. Methods and Results—In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1.46 pg/mL; P=0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration (P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P=0.005); for each quartile increase in IL-6, there was a 38% increase in risk (P=0.001).This relationship...

Triggering of sudden death from cardiac causes by vigorous exertion

Abstract: Background Retrospective and cross-sectional data suggest that vigorous exertion can trigger cardiac arrest or sudden death and that habitual exercise may diminish this risk. However, the role of physical activity in precipitating or preventing sudden death from cardiac causes has not been assessed prospectively in a large number of subjects. Methods We used a prospective, nested case–crossover design within the Physicians' Health Study to compare the risk of sudden death during and up to 30 minutes after an episode of vigorous exertion with that during periods of lighter exertion or none. We then evaluated whether habitual vigorous exercise modified the risk of sudden death that was associated with vigorous exertion. In addition, the relation of vigorous exercise to the overall risk of sudden death and nonsudden death from coronary heart disease was assessed. Results During 12 years of follow-up, 122 sudden deaths were confirmed among the 21,481 male physicians who were initially free of self-reported ca...

Systolic and Diastolic Blood Pressure, Pulse Pressure, and Mean Arterial Pressure as Predictors of Cardiovascular Disease Risk in Men

Abstract: —We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting the risk of cardiovascular disease (CVD), stratifying results at age 60 years, when DBP decreases while SBP continues to increase. We prospectively followed 11 150 male physicians with no history of CVD or antihypertensive treatment through the 2-year questionnaire, after which follow-up began. Reported blood pressure was averaged from both the baseline and 2-year questionnaires. During a median follow-up of 10.8 years, there were 905 cases of incident CVD. For men aged P >0.05). For men aged ≥60 years (n=2407), those in the highest versus lowest quartiles of average SBP (≥135 versus P >0.05). These data suggest that average SBP, DBP, and MAP strongly predict CVD among younger men, whereas either average SBP or PP predicts CVD among older men. More research should distinguish whether MAP, highly correlated with SBP and DBP, better predicts CVD.

Baseline Characteristics of Participants in the Women's Health Study

Abstract: The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial designed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in women. A total of 39,876 female health professionals, age 45 years or older and without a history of cardiovascular disease or cancer (other than nonmelanoma skin cancer), were randomized in a 2 X 2 factorial design to one of four treatment groups: active aspirin and vitamin E placebo, aspirin placebo and active vitamin E, both active agents, or both placebos. The process of randomization was successful, as evidenced by the equal distribution of a large number of baseline demographic, lifestyle, and health history characteristics among the four treatment groups. Similar distribution of known potential confounders, as well as the large sample size, provides reassuring evidence that unmeasured or unknown potential confounders are also equally distributed. As expected in...

Blood Levels of Homocysteine and Increased Risks of Cardiovascular Disease: Causal or Casual?

Abstract: Background Accumulating data from epidemiological studies suggest that individuals with elevated blood levels of homocysteine have increased risks of cardiovascular disease. We reviewed the currently available evidence of an association between homocysteine and cardiovascular disease and examined whether the strength of the evidence varies according to study design. Methods We used a computerized MEDLINE literature search, 1966 through September 1998, to identify all epidemiological studies that examined the relationship of homocysteine level with risks of coronary heart or cerebrovascular disease. Two measures of plasma homocysteine level and its association with risk of cardiovascular disease were extracted: mean homocysteine level in cases and controls, and relative risk of cardiovascular disease for elevated homocysteine level. Results A total of 43 studies were reviewed. Most cross-sectional and case-control studies indicated higher mean homocysteine levels (either fasting or after methionine load) and/or a greater frequency of elevated homocysteine level in persons with cardiovascular disease as compared with persons without cardiovascular disease. Results of most prospective studies, however, indicated smaller or no association. The few prospective studies that reported a positive association between homocysteine level and risks of cardiovascular disease included patients with preexisting vascular disease. Conclusions In contrast to cross-sectional and case-control studies, results of prospective studies indicated less or no predictive ability for plasma homocysteine in cardiovascular disease. Instead, elevated homocysteine level may be an acute-phase reactant that is predominantly a marker of atherogenesis, or a consequence of other factors more closely linked to risks of cardiovascular disease. Randomized trials are necessary to test reliably whether lowering homocysteine levels will decrease risks of cardiovascular disease.

Pulse pressure and mortality in older people.

Abstract: Background: In older people, observational data are unclear concerning the relationships of systolic and diastolic blood pressure with cardiovascular and total mortality. We examined which combinations of systolic, diastolic, pulse, and mean arterial pressure best predict total and cardiovascular mortality in older adults. Methods: In 1981, the National Institute on Aging initiated its population-based Established Populations for Epidemiologic Studies of the Elderly in 3 communities. At baseline, 9431 participants, aged 65 to 102 years, had blood pressure measurements, along with measures of medical history, use of medications, disability, and physical function. During an average follow-up of 10.6 years among survivors, 4528 participants died, 2304 of cardiovascular causes. Results: In age- and sex-adjusted survival analyses, the lowest overall death rate occurred among those with systolic pressure less than 130 mm Hg and diastolic pressure 80 to 89 mm Hg; relative to this group, the highest death rate occurred in those with systolic pressure of 160 mm Hg or more and diastolic pressure less than 70 mm Hg (relative risk, 1.90; 95% confidence interval, 1.47-2.46). Both low diastolic pressure and elevated systolic pressure independently predicted increases in cardiovascular (P,.001) and total (P,.001) mortality. Pulse pressure correlated strongly with systolic pressure (R=0.82) but was a slightly stronger predictor of both cardiovascular and total mortality. In a model containing pulse pressure and other potentially confounding variables, diastolic pressure (P=.88) and mean arterial pressure (P=.11) had no significant association with mortality. Conclusions: Pulse pressure appears to be the best single measure of blood pressure in predicting mortality in older people and helps explain apparently discrepant results for low diastolic blood pressure. Arch Intern Med. 2000;160:2765-2772

A Prospective Study of Walking as Compared with Vigorous Exercise in the Prevention of Coronary Heart Disease in Women

Abstract: Background The role of walking, as compared with vigorous exercise, in the prevention of coronary heart disease remains controversial, and data for women on this topic are sparse. Methods We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). Results There was a strong, graded inverse association between physical activity and the risk of coronary events. As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend or =6 MET) was associated with similar risk reductions (30 to 40 percent). Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary. Conclusions These prospective data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women.

Alcohol consumption and risk of Type 2 diabetes mellitus among US male physicians

Abstract: Objective To examine the association between low to moderate alcohol consumption and the incidence of type 2 diabetes mellitus (DM) in men. Design Prospective cohort study. Subjects and Methods Over an average period of 12.1 years, we evaluated 20,951 participants in the Physicians' Health Study between ages 40 and 84 years who were free of cardiovascular disease, cancer, and diabetes and provided data on alcohol consumption at baseline. Main Outcome Measure Type 2 DM diagnosed after randomization. Results Among 20,951 physicians, 766 cases of incident DM were reported over an average follow-up period of 12.1 years. After adjustment for age, randomized treatment assignment, smoking, physical activity, and body mass index, the relative risk estimates and 95% confidence intervals for those reporting alcohol use of rarely/never, 1 to 3 drinks per month, 1 drink per week, 2 to 4 drinks per week, 5 to 6 drinks per week, and 1 or more drinks per day were 1.00 (referent), 1.03 (0.80-1.33), 0.89 (0.70-1.14), 0.74 (0.59-0.93), 0.67 (0.51-0.89), and 0.57 (0.45-0.73), respectively (linear trend, P Conclusion These data indicate that apparently healthy men who self-select for light to moderate alcohol consumption have a decreased subsequent risk of type 2 DM.

Male pattern baldness and coronary heart disease: the Physicians' Health Study.

Abstract: moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59), and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, ,.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12). Conclusion: Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels. Arch Intern Med. 2000;160:165-171

Seven-year changes in alcohol consumption and subsequent risk of cardiovascular disease in men

Abstract: Background: Few studies have examined whether changes in alcohol consumption influence future cardiovascular risk. Objective: To examine whether 7-year changes in alcohol consumption are associated with the subsequent risk of cardiovascular disease (CVD). Methods: We prospectively followed up 18455 men aged 40 to 84 years from the Physicians’ Health Study with no history of CVD or cancer. Alcohol consumption was reported on the baseline and the 7-year questionnaires; follow-up for this analysis began after the 7-year questionnaire (median follow-up, 5.8 years). There were 1091 CVD cases, including myocardial infarction, angina pectoris, revascularization, stroke, and CVD-related death. Results: Among men initially consuming 1 drink per week or less (n=7360), those with moderate increases (.1 to ,6 drinks per week) in alcohol consumption had a borderline significant (P=.05) 29% reduced risk of CVD compared with men with no changes (˛1 to 1 drink per week). Among men initially consuming greater than 1 to 6 drinks per week (n=6612), those with moderate increases had a nonsignificant (P=.32) 15% decrease in CVD risk compared with men with no changes. Finally, among men initially consuming 1 drink per day or more (n=4483), those who increased intake had a 63% increased risk of CVD compared with men with no changes. Conclusions: These prospective data suggest that, among men with initially low alcohol consumption (#1 drink per week), a subsequent moderate increase in alcohol consumption may lower their CVD risk. The possible reduction in CVD risk from increasing alcohol intake did not extend to men initially consuming greater than 1 drink per week. Given the potential risks and benefits associated with alcohol consumption, physician counseling of patients must be individualized in the context of the primary prevention of CVD. Arch Intern Med. 2000;160:2605-2612

A prospective study of physical activity and risk of prostate cancer in US physicians

Abstract: Background Exercise can suppress androgen production and may thus decrease the risk of prostate cancer. However, findings from epidemiological studies assessing physical activity and risk of prostate cancer are inconsistent. Methods We prospectively examined the association between physical activity and prostate cancer risk in the Physicians' Health Study (PHS), a randomized trial of low-dose aspirin and beta-carotene among 22 071 men aged 40-84 without self-reported myocardial infarction, stroke and cancer. At baseline in 1982, men were asked about the frequency of exercise vigorous enough to work up a sweat. Physical activity was assessed in a similar fashion again at 36 months of follow-up. Results During 11.1 years of follow-up (258 779 person-years), 982 cases of prostate cancer occurred and were confirmed by medical record review. After adjustment for potential confounding factors (including age, height, randomized treatment assignment, smoking status, alcohol intake, use of multivitamins, history of diabetes, history of hypertension and history of high cholesterol), the relative risks for prostate cancer associated with exercise vigorous enough to work up a sweat were 1.0 (referent) for frequency less than once per week, 1.02 (95% CI : 0.82-1.26) for once per week, 1.07 (95% CI : 0.90-1.27) for 2-4 times per week, and 1.11 (95% CI : 0.90-1.36) for 5+ times per week. Across all subgroups of men categorized by age, body mass index, smoking status, alcohol intake, use of multivitamins, history of diabetes, history of hypertension and history of high cholesterol, there were no significant associations between frequency of exercise vigorous enough to work up a sweat and prostate cancer risk. After excluding cases of prostate cancer that occurred during the first 36 months of follow-up, again, there was no significant association. Combining physical activity assessments at baseline and at 36 months also yielded no significant association with prostate cancer risk. Conclusions These observational data from the Physicians' Health Study do not support the hypothesis that increased physical activity reduces the risk of prostate cancer.

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease.

Abstract: Background In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. Objective To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. Methods and Results These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease–related death (1%; 95% CI, −12% to 16%) and nonfatal stroke (8%; 95% CI, −12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. Conclusions For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease–related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.

Self-Selected Posttrial Aspirin Use and Subsequent Cardiovascular Disease and Mortality in the Physicians' Health Study

Abstract: Background The randomized aspirin component of the Physicians' Health Study (PHS) was terminated early, after 5 years, primarily because of the emergence of a statistically extreme (P Methods Data on self-selected aspirin use were collected until the beta carotene component ended as scheduled after 12 years. Posttrial use of aspirin was assessed at the 7-year follow-up among 18 496 participants with no previous reported CVD. Randomized and posttrial observational results in the PHS were compared, and differences between those self-selecting aspirin and those not were examined. Results At 7 years, 59.5% of participants without CVD reported self-selected aspirin use for at least 180 d/y, and 20.8% for 0 to 13 d/y. Use was significantly associated with family history of MI, hypertension, elevated cholesterol levels, body mass index, alcohol consumption, exercise, and use of vitamin E supplements. In multivariate analyses, self-selected aspirin use for at least 180 vs 0 to 13 d/y was associated with lower risk for subsequent MI (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55-0.95), no relation with stroke (RR, 1.02; 95% CI, 0.74-1.39), and significant reductions in CVD-related (RR, 0.65; CI, 0.47-0.89) and total mortality (RR, 0.64; CI, 0.54-0.77). Conclusion These associations between self-selected aspirin use and CVD risk factors increase the likelihood of residual confounding and emphasize the need for large-scale randomized trials, such as the ongoing Women's Health Study, to detect reliably the most plausible small to moderate effects of aspirin in the primary prevention of stroke and CVD-related death.

A prospective study of cytochrome P450 1A1 polymorphisms and colorectal cancer risk in men.

Abstract: Positive associations with increased red meat intake and colorectal cancer have been reported consistently [(1)][1] , particularly with the consumption of broiled and grilled meats [(2)][2] . This may be attributable to PAH[4][3] formation. Cigarette smoking is another source of PAH exposure, and an

Antioxidant Vitamins and Cardiovascular Disease: Evidence from Observational Epidemiologic Studies and Randomized Trials

Abstract: Despite the proliferation of advertisements touting the benefits of antioxidant vitamins on cardiovascular disease in consumer magazines and on the Internet, this hypothesis has not yet been proven. Basic science and animal research studies have provided plausible biologic mechanisms and some, but not all, observational epidemiologic studies indicate that individuals who self-select for antioxidant vitamins have decreased risks of cardiovascular disease. However, since the benefits postulated are small to moderate in size, the most reliable data on which to base public health recommendations regarding the use of antioxidant supplements will be provided by large-scale randomized trials of sufficient size, dose, and duration. Ultimately, a judgment of benefit, no effect, or harm associated with the use of antioxidant vitamins must be based on an evaluation of the totality of evidence from all these research disciplines.

Marqueurs inflammatoires systemiques en tant qu'outils diagnostiques dans la prevention des maladies atherosclereuses

Abstract: L'invention concerne des procedes servant a caracteriser, chez un individu, un profil de risque de developpement futur d'une maladie cardio-vasculaire, et consistant a obtenir un niveau du marqueur d'inflammation systemique de cet individu. L'invention concerne egalement des procedes d'evaluation de la possibilite qu'un traitement, a base d'un agent reduisant le risque de developpement futur d'une maladie cardio-vasculaire, va etre benefique pour un individu.