Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD.     

Chronic psychosocial stress predicts long-term cardiovascular morbidity and mortality in middle-aged men.

AIMS: To prospectively investigate the association between self-reported psychosocial stress and long-term cardiovascular (CV) morbidity and mortality in a population-based cohort. METHODS AND RESULTS: The Malm? Preventive Project is a population-based screening and intervention programme for cardiovascular disease (CVD) risk factors. Between 1974 and 1980, a total of 13,609 (2741 women) individuals, mean age 45 years, had self-reported chronic stress determined by questionnaire. CV morbidity and mortality were followed up in national registries. Median follow-up time was 21 years. The risk ratio (RR) for a fatal or nonfatal CV incident in the men and women of the group reporting chronic stress was 1.27 (95% CI 1.15-1.39). After stepwise adjustments for known CV risk factors, the RR was reduced to 1.14 (1.02-1.28). The highest RR was found for fatal stroke in men reporting chronic stress, 2.04 (1.07-3.88). For women alone, there was no significant increase in risk after adjustments. CONCLUSION: Self-reported chronic stress is an independent risk factor for CVD, particularly fatal stroke, in middle-aged men; it continues to be a risk factor after adjustment for several other known risk factors. The adjustment itself might reflect mechanisms whereby psychosocial stress directly or indirectly exerts its effects on the body, indicating a possible over-adjustment.     

Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus

BACKGROUND: Although the association between smoking and increased risk of coronary heart disease (CHD) is well established in the general population, this relationship is less well-defined among individuals with diabetes. OBJECTIVE: To assess the relationship between cigarette smoking and risk of CHD among women with type 2 diabetes mellitus in the Nurses' Health Study cohort. METHODS: The Nurses' Health Study, a prospective cohort study of 121,700 US female registered nurses surveyed in 11 states and followed up from July 1, 1976, through July 1, 1996, involved a total of 6547 women diagnosed as having type 2 diabetes mellitus. Incident cases of CHD were our main outcome measure in this study. RESULTS: We documented 458 incident cases of CHD (200 fatal CHD-related cases and 258 nonfatal myocardial infarctions) during 20 years (68,227 person-years) of follow-up. We found a dose-response relationship between current smoking status and risk of CHD among diabetic women. Compared with never smokers, the relative risks (RRs) for CHD were 1.21 (95% confidence interval [CI], 0.97-1.51) for past smokers, 1.66 (95% CI, 1.10-2.52) for current smokers of 1 to 14 cigarettes per day, and 2.68 (95% CI, 2.07-3.48) for current smokers of 15 or more cigarettes per day in multivariate analyses (P<.001 for trend). The multivariate RR of CHD among diabetic women who had stopped smoking for more than 10 years was similar to that among diabetic women who were never smokers (RR, 1.01; 95% CI, 0.73-1.38). In secondary analyses involving diabetic and nondiabetic women, the multivariate-adjusted RR of CHD for those with diabetes who currently smoked (> or = 15 cigarettes per day) compared with those who never smoked was 7.67 (95% CI, 5.88-10.01). CONCLUSIONS: Cigarette smoking is strongly associated with an increased risk of CHD among women with type 2 diabetes mellitus. Furthermore, quitting smoking seems to decrease this excess risk substantially; women with diabetes should be strongly advised against smoking.CK     

Age at natural menopause and risk of cardiovascular disease.

BACKGROUND: Early natural menopause has been postulated to increase the risk of cardiovascular disease. OBJECTIVE: To examine the relation of age at natural menopause with risk of coronary heart disease (CHD) and stroke in the Nurses' Health Study. METHODS: Analysis was restricted to 35 616 naturally postmenopausal women who never used estrogen replacement therapy and with no diagnosed cardiovascular disease at baseline, followed up from 1976 to 1994. Information on menopausal status, age at menopause, and other risk factors was obtained in 1976 and updated every 2 years by mailed questionnaires. RESULTS: During 354326 person-years of follow-up, we documented 757 incident cases of CHD and 350 incident cases of stroke. After adjusting for age, smoking status, and other cardiovascular risk factors, the relative risks (RRs) across categories of age at natural menopause (<40, 40-44, 45-49, 50-54, and > or = 55 years) were 1.53, 1.42, 1.10, 1.00 (reference), and 0.95, respectively; the RR for each 1-year decrease in age at natural menopause was 1.03 (95% confidence interval, 1.01-1.05). Elevated risk with younger age at menopause was observed among current smokers (RR, 1.04 [95% CI, 1.01-1.07] for each 1-year decrease in age at natural menopause) but not among never smokers (RR, 1.00; 95% CI, 0.96-1.04). Age at natural menopause was not significantly associated with ischemic stroke (RR, 1.01; 95% CI, 0.97-1.04) or hemorrhagic stroke (RR, 1.03; 95% CI, 0.97-1.10). CONCLUSIONS: We observed an overall significant association between younger age at menopause and higher risk of CHD among women who experienced natural menopause and never used hormone therapy. This increased risk was observed among current smokers but not among never smokers. The apparent elevated risk of CHD with decreased age at natural menopause among smokers might reflect residual confounding by smoking.     

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.     

Adiponectin and incident coronary heart disease and stroke. A systematic review and meta‐analysis of prospective studies

The plasma concentration of adiponectin, an adipokine that has anti‐inflammatory, anti‐atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta‐analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using ‘adiponectin’ and ‘cardiovascular disease’ or ‘stroke’ and their synonyms, excluding patients with clinically manifest vascular disease. Random‐effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose–response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta‐analyses. An increase of 1 standard deviation in log‐transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86–1.09). A 10 μg mL^–1 increase in adiponectin conferred a RR of 0.91 (95% CI 0.80–1.03) for CHD and a RR 1.01 (95% CI 0.97–1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.     

Dietary magnesium intake and risk of cardiovascular disease among women

This study assessed the hypothesis that greater magnesium intake is associated with reduced risk for cardiovascular disease (CVD), including myocardial infarction (MI) and stroke, in a large prospective cohort of women. In 1993, a semi-quantitative food frequency questionnaire was used to assess magnesium intake in 39,876 female health professionals aged 39 to 89 years who had no history of CVD or cancer. During a median of 10 years of follow-up, 1,037 incident cases of CVD were identified, including 280 nonfatal MIs and 368 strokes. After adjustment for age and randomized treatment status, magnesium intake was not significantly associated with risk for incident CVD. Comparing the highest quintile of magnesium intake (median 433 mg/day) with the lowest quintile (median 255 mg/day), the relative risks were 0.87 (95% confidence interval [CI] 0.72 to 1.05, p for trend = 0.24) for total CVD, 0.88 (95% CI 0.70 to 1.12, p for trend = 0.34) for coronary heart disease (CHD), 1.03 (95% CI 0.72 to 1.49, p for trend = 0.96) for nonfatal MI, 1.11 (95% CI 0.61 to 2.00, p for trend = 0.95) for CVD death, and 0.87 (95% CI 0.64 to 1.18, p for trend = 0.55) for total stroke. Additional adjustment for other CVD risk factors did not materially change the observed null associations. In conclusion, the results do not support the hypothesis that magnesium intake reduces the development of CHD, although a modest inverse association with stroke cannot be ruled out.     

Vitamin C and risk of coronary heart disease in women

OBJECTIVES: Our objective was to prospectively examine the relation between vitamin C intake and risk of coronary heart disease (CHD) in women. BACKGROUND: Results from prospective investigations of the relation between vitamin C intake and risk of CHD have been inconsistent. The lack of clear evidence for a protective association despite a plausible mechanism indicates the need to evaluate further the association between vitamin C intake and risk of CHD. METHODS: In 1980, 85,118 female nurses completed a detailed semiquantitative food-frequency questionnaire that assessed their consumption of vitamin C and other nutrients. Nurses were followed up for 16 years for the development of incident CHD (nonfatal myocardial infarction and fatal CHD). RESULTS: During 16 years of follow-up (1,240,566 person-years), we identified 1,356 incident cases of CHD. After adjustment for age, smoking, and a variety of other coronary risk factors, we observed a modest significant inverse association between total intake of vitamin C and risk of CHD (relative risk [RR] = 0.73; 95% confidence interval [CI] 0.57 to 0.94). Among women who did not use vitamin C supplements or multivitamins, the association between intake of vitamin C from diet alone and incidence of CHD was weak and not significant (RR = 0.86; 95% CI 0.59 to 1.26). In multivariate models adjusting for age, smoking, and a variety of other coronary risk factors, vitamin C supplement use was associated with a significantly lower risk of CHD (RR = 0.72; 95% CI 0.61 to 0.86). CONCLUSIONS: Users of vitamin C supplements appear to be at lower risk for CHD.     

Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses' Health Study

OBJECTIVE: To explore the contribution of female hormonal factors occurring prior to the onset of rheumatoid arthritis (RA), such as age at menarche, parity, age at first birth, breast-feeding, use of oral contraceptives (OCs), irregular menstrual cycles, and postmenopausal hormone (PMH) use, to the subsequent development of RA in a large female cohort. METHODS: We studied female reproductive and hormonal risk factors for RA in a cohort of 121,700 women enrolled in the longitudinal Nurses' Health Study. The diagnosis of incident RA (between 1976 and 2002) in 674 women was confirmed by a connective tissue disease screening questionnaire and blinded medical record review for American College of Rheumatology criteria. Sixty percent of the patients with RA were rheumatoid factor positive. The relationship between potential risk factors, including age, age at menarche, parity, age at first birth, total lifetime history of breast-feeding, use of OCs, and irregular menstrual cycles and the multivariate-adjusted risk of RA was estimated using Cox proportional hazards models. RESULTS: Using a multivariate model that adjusted for age, body mass index, smoking, parity, and other hormonal factors, we observed a strong trend for decreasing risk of RA with increasing duration of breast-feeding (P for trend = 0.001). For women who breast-fed (compared with parous women who did not breast-feed), the risk ratios (RRs) and 95% confidence intervals (95% CIs) were as follows: breast-feeding for < or =3 total months, RR 1.0 (95% confidence interval [95% CI] 0.8-1.2); for 4-11 total months, RR 0.9 (95% CI 0.7-1.1); for 12-23 total months, RR 0.8 (95% CI 0.6-1.0); and for > or =24 total months, RR 0.5 (95% CI 0.3-0.8). Very irregular menstrual cycles were associated with an increased risk of RA (RR 1.4, 95% CI 1.0-2.0). Age at menarche < or =10 years was associated with an increased risk of seropositive RA (RR 1.6, 95% CI 1.1-2.4) but not significantly associated with risk of RA. Parity, total number of children, age at first birth, and OC use were not associated with an increased risk of RA in this cohort. CONCLUSION: In this large cohort, breast-feeding for >12 months was inversely related to the development of RA. This apparent effect was dose-dependent, with a significant trend toward lower risk with longer duration of breast-feeding. Irregular menstrual cycles and earlier age at menarche increased the risk of RA. Other reproductive hormonal factors were not associated with RA risk.     

Disability and Incident Coronary Heart Disease in Older Community‐Dwelling Adults: The Three‐City Study

OBJECTIVES: To prospectively assess the association between disability and incident fatal and nonfatal coronary heart disease (CHD) in older adults free of cardiovascular disease (CVD). DESIGN: A French multicenter prospective population‐based cohort of 9,294 subjects, aged 65 and older at baseline, recruited between 1999 and 2001 and followed for 6 years. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: Seven thousand three hundred fifty‐four participants with no history of CVD and with available information on disability status. Subjects were categorized at baseline as having no disability, mild disability (mobility only), and moderate or severe disability (mobility plus activities of daily living or instrumental activities of daily living). MEASUREMENTS: Incident fatal and nonfatal coronary events (angina pectoris, myocardial infarction, revascularization procedures, and CHD death). RESULTS: At baseline, the mean level of the risk factors increased gradually with the severity of disability. After a median follow‐up of 5.2 years, 264 first coronary events, including 55 fatal events, occurred. After adjustment for cardiovascular risk factors, participants with moderate or severe disability had a 1.7 times (95% confidence interval (CI)=1.0–2.7) greater risk of overall CHD than nondisabled subjects, whereas those with mild disability were not at greater CHD risk. An association was also found with fatal CHD, for which the risk increased gradually with the severity of disability (hazard ratio (HR)_{mild disability}=1.7, 95% CI=0.8–3.6; HR_{moderate/severe disability}=3.5, 95% CI=1.3–9.3; P for trend=.01). CONCLUSION: In older community‐dwelling adults, the association between disability and incident CHD is mostly due to an association with fatal CHD.     

Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group

Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.     

Waist circumference,body mass index,and risk for stroke in older people: a 15 year longitudinal population study of 70- year-olds

OBJECTIVES: To investigate waist circumference (WC) and body mass index (BMI) at age 70 as risk factors for stroke. DESIGN: Cohort study of 70-year-olds with 15-year follow-up. SETTING: Geriatric Medicine Department, G?teborg University, Sweden. PARTICIPANTS: Two thousand two hundred eighty-seven (1,045 men; 1,242 women) 70-year-olds examined between 1971 and 1981 in G?teborg, Sweden. MEASUREMENTS: Cox regression model was used to calculate relative risk (RR) and 95% confidence interval (CI) for first-ever stroke (fatal and nonfatal) in reference to the lowest quartiles of WC and BMI. Tests for trend were performed fitting WC and BMI in their original continuous form. RESULTS: In men and women, RRs for stroke, in the highest WC quartile were 1.65 (95% CI = 1.08-2.51) and 1.31 (95% CI = 0.88-1.92), respectively, after adjustment for cohorts, smoking habit, coronary heart disease (CHD), diabetes mellitus, total cholesterol (TC), systolic blood pressure (SBP), and height at age 70. In men, RR for stroke in the highest BMI quartile (> or=28 kg/m2) was 1.68 (95% CI = 1.12-2.53) after adjustment for cohorts, smoking habits, CHD, diabetes mellitus, TC, and SBP at age 70. In women, adjusted RRs for stroke across the BMI quartiles were not significantly different. In men, population attributable fractions of stroke were 24.8% and 25.2% for the highest quartiles of WC and BMI, respectively. CONCLUSIONS: High WC (> or =99 cm) and BMI (> or =28 kg/m2) are risks for stroke in older men but not in older women.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study

BACKGROUND: Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women. METHODS: In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women's Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality. RESULTS: At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein. CONCLUSIONS: The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.     

Association between aspirin use and cardiovascular outcomes in ALLHAT participants with and without chronic kidney disease: A post hoc analysis

It is unclear whether aspirin is beneficial for prevention of CVD in patients with CKD. We performed a secondary analysis of the ALLHAT trial to assess the effect of baseline aspirin use on nonfatal myocardial infarction (MI) or fatal coronary heart disease (CHD), all‐cause mortality, and stroke. Baseline characteristics of aspirin users and nonusers were used to generate propensity‐matched cohorts. Using conditional Cox proportional hazard regression models, we examined the effect of aspirin on the outcomes in the cohort at large and across 3 levels of kidney function (eGFR ≥90, 60–89, and <60). 11 250 ALLHAT participants reported using aspirin at baseline. The propensity‐matched dataset included 6894 nonusers matched with replacement to achieve a balanced analysis population (n = 22 500). Risk of fatal CHD or nonfatal MI (HR = 0.94, 95% CI 0.86–1.02) and stroke (HR = 1.01, 95% CI 0.89–1.15) was not significantly different between groups. Aspirin users were at significantly lower risk of all‐cause mortality compared to nonusers (HR = 0.82, 95% CI 0.76–0.88). Aspirin use was not associated with incidence of fatal CAD or nonfatal MI in patients with CVD (HR = 0.93, CI 0.84–1.04) or without CVD at baseline (HR = 1.04, CI 0.82–1.32). Results were consistent across strata of GFR (interaction p value NS). In hypertensive patients at high cardiovascular risk, aspirin use is not associated with risk of nonfatal MI, fatal CHD, or stroke; however, aspirin use is associated with lower risk of all‐cause mortality. These results are consistent across baseline eGFR.     

Do breast‐feeding and other reproductive factors influence future risk of rheumatoid arthritis?: Results from the Nurses' Health Study

Objective

To explore the contribution of female hormonal factors occurring prior to the onset of rheumatoid arthritis (RA), such as age at menarche, parity, age at first birth, breast‐feeding, use of oral contraceptives (OCs), irregular menstrual cycles, and postmenopausal hormone (PMH) use, to the subsequent development of RA in a large female cohort.

Methods

We studied female reproductive and hormonal risk factors for RA in a cohort of 121,700 women enrolled in the longitudinal Nurses' Health Study. The diagnosis of incident RA (between 1976 and 2002) in 674 women was confirmed by a connective tissue disease screening questionnaire and blinded medical record review for American College of Rheumatology criteria. Sixty percent of the patients with RA were rheumatoid factor positive. The relationship between potential risk factors, including age, age at menarche, parity, age at first birth, total lifetime history of breast‐feeding, use of OCs, and irregular menstrual cycles and the multivariate‐adjusted risk of RA was estimated using Cox proportional hazards models.

Results

Using a multivariate model that adjusted for age, body mass index, smoking, parity, and other hormonal factors, we observed a strong trend for decreasing risk of RA with increasing duration of breast‐feeding (P for trend = 0.001). For women who breast‐fed (compared with parous women who did not breast‐feed), the risk ratios (RRs) and 95% confidence intervals (95% CIs) were as follows: breast‐feeding for ≤3 total months, RR 1.0 (95% confidence interval [95% CI] 0.8‐1.2); for 4–11 total months, RR 0.9 (95% CI 0.7–1.1); for 12–23 total months, RR 0.8 (95% CI 0.6–1.0); and for ≥24 total months, RR 0.5 (95% CI 0.3–0.8). Very irregular menstrual cycles were associated with an increased risk of RA (RR 1.4, 95% CI 1.0–2.0). Age at menarche ≤10 years was associated with an increased risk of seropositive RA (RR 1.6, 95% CI 1.1–2.4) but not significantly associated with risk of RA. Parity, total number of children, age at first birth, and OC use were not associated with an increased risk of RA in this cohort.

Conclusion

In this large cohort, breast‐feeding for >12 months was inversely related to the development of RA. This apparent effect was dose‐dependent, with a significant trend toward lower risk with longer duration of breast‐feeding. Irregular menstrual cycles and earlier age at menarche increased the risk of RA. Other reproductive hormonal factors were not associated with RA risk.

     

Fatty liver and uric acid levels predict incident coronary heart disease but not stroke among atomic bomb survivors in Nagasaki.

Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0 +/- 9.9 years old; 1,249 women: 63.2 +/- 8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01-1.08), smoking (RR 2.20, 95% CI 1.02-4.74), hyperuricemia (RR 2.30, 95% CI 1.08-4.89), and fatty liver (RR 2.53, 95% CI 1.06-6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06-1.10), smoking (RR 2.06, 95% CI 1.14-3.72), and hypertension (RR 2.14, 95% CI 1.38-3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.     

Metabolic syndrome vs Framingham Risk Score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus

BACKGROUND: We sought to compare metabolic syndrome (MetS) with the Framingham Risk Score (FRS) as predictors of coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (DM2) in middle-aged men. METHODS: A prospective study of 5128 men aged 40 to 59 years with no history of cardiovascular disease (CVD) (CHD or stroke) or DM2 drawn from general practices in 24 British towns and observed for 20 years. Metabolic syndrome was defined as the presence of 3 or more metabolic abnormalities based on modified National Cholesterol Education Program criteria. RESULTS: Men with MetS at baseline (26%) showed significantly higher relative risk (RR) than men without MetS of developing CHD (RR, 1.64; 95% confidence interval [CI], 1.41-1.90), stroke (RR, 1.61 95% CI, 1.26-2.06), and DM2 (RR, 3.57; 95% CI, 2.83-4.50). The probability of developing CVD or DM2 over 20 years increased from 11.9% in those with no abnormalities to 31.2% in those with 3 abnormalities to 40.8% in those with 4 or 5 abnormalities. The FRS was a better predictor of CHD and stroke than MetS but was less predictive of DM2. Areas under the receiver-operating characteristic curves for FRS vs the number of metabolic abnormalities were 0.68 vs 0.59 for CHD, 0.60 vs 0.70 for DM2, and 0.66 vs 0.55 for stroke (P< .001 for all). CONCLUSIONS: Presence of MetS is a significant predictor of CVD and DM2 but is a stronger predictor of DM2 than of CHD. Although MetS does not predict CHD as well as the FRS, it serves well as a simple clinical tool for identifying high-risk subjects predisposed to CVD or DM2.     

Menstrual cycle irregularity as a marker of cardiovascular risk factors at postmenopausal years

To evaluate the association between cardiovascular risk factors (CVRF) during postmenopausal years and previous menstrual irregularity during reproductive years, we performed a case-control study in 414 postmenopausal women (mean age 60.4 +/- 5.5 years; BMI 25.3 +/- 4.7 kg/m(2)). The variables assessed were: menstrual cycle characteristics at age 2035y (independent) and records of arterial hypertension, dyslipidemia, diabetes mellitus, and coronary heart disease (dependent). Statistical analysis used the chi-square test and logistic regression, adjusting for potential confounders for cardiovascular risk, with significance set at 5%. Women reporting previous menstrual irregularity were associated with increased risk for some CVRF [adjusted odds ratio (OR) 2.14; CI-95%=1,024.48], when compared with those reporting regular menstrual cycles. Stratified analysis demonstrated significant associations of previous menstrual irregularity with: arterial hypertension (OR= 2.74; CI-95%=1,395.41), hypercholesterolemia (OR= 2.32; CI-95%=1,174.59)), hypertriglyceridemia (OR= 2.09; CI-95%=1,104.33), and coronary angioplasty (OR= 6.82; CI-95%=1,4432.18). These data suggest that a prior history of menstrual irregularity, as indicative of polycystic ovary syndrome, may be related to increased risk for CVD during postmenopausal years.     

A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study.

BACKGROUND--Although dietary factors are suspected to be important determinants of coronary heart disease (CHD) risk, the direct evidence is relatively sparse. METHODS--The Adventist Health Study is a prospective cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists. Extensive dietary information was obtained at baseline, along with the values of traditional coronary risk factors. These were related to risk of definite fatal CHD or definite nonfatal myocardial infarction. RESULTS--Subjects who consumed nuts frequently (more than four times per week) experienced substantially fewer definite fatal CHD events (relative risk, 0.52; 95% confidence interval [CI], 0.36 to 0.76) and definite nonfatal myocardial infarctions (relative risk, 0.49; 95% CI, 0.28 to 0.85), when compared with those who consumed nuts less than once per week. These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population. Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infarction (relative risk, 0.56; 95% CI, 0.35 to 0.89) and definite fatal CHD (relative risk, 0.89; 95% CI, 0.60 to 1.33) when compared with those who usually ate white bread. Men who ate beef at least three times each week had a higher risk of definite fatal CHD (relative risk, 2.31; 95% CI, 1.11 to 4.78), but this effect was not seen in women or for the nonfatal myocardial infarction end point. CONCLUSION--Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events. The favorable fatty acid profile of many nuts is one possible explanation for such an effect.