A prospective evaluation of the risk of QT prolongation with hormone replacement therapy: the atherosclerosis risk in communities study

PURPOSE: Prolongation of the QT interval is associated with an increased risk of arrhythmia, coronary heart disease (CHD), and mortality. Estrogens and androgens have been proposed as a causal factor in QT lengthening. We tested whether postmenopausal hormone replacement therapy was associated with prolonged QT intervals in a healthy population sample of women (mean age=54). METHODS: Women (n=3103) were asked about estrogen (ERT) and progestin plus estrogen (PERT) replacement therapy use at 4 examinations over 9 years. Electrocardiographic QT intervals were measured and corrected for heart rate using the QT Index (QTI) and Bazett's correction. QT prolongation was defined as QTI>110% and a change from baseline of >or=4%. RESULTS: Heart rate corrected QT length was moderately but significantly (p<0.01) greater, and the risk of QT prolongation was nearly twice (Odds Ratio=1.9, 95% Confidence Interval: 1.2-2.0) that in women who used ERT compared with never users. PERT use was not significantly associated with QT length. CONCLUSIONS: The potential for slight increases in QT length over time, and an increased risk of QT prolongation with ERT use identified in this observational study, are important concerns that should be further explored in randomized trials.     

Relation between cognitive function and mortality in middle-aged adults: the atherosclerosis risk in communities study

An independent, inverse association between cognitive function and all-cause mortality has been reported in elderly cohorts. The purpose of this study was to determine whether the same association exists in middle-aged persons. The Atherosclerosis Risk in Communities Study is a cohort study initiated in 1987 to investigate the development of atherosclerosis in middle-aged persons. Three cognitive function measures were included in the second cohort examination conducted from 1990 to 1992 when the participants were aged 48-67 years: the Delayed Word Recall Test (DWRT), the Digit Symbol Substitution Test (DSST) (a subtest from the Wechsler Adult Intelligence Scale-Revised), and the Word Fluency Test from the Multilingual Aphasia Examination. Cox proportional hazards modeling was used to determine whether all-cause mortality ascertained through 1997 was associated with each measure after adjustment for sociodemographic, biologic, psychologic, and behavioral risk factors. Without adjustment, there was a significantly lower mortality hazard associated with higher scores on all three measures. After covariate adjustment, the hazard ratios for the DWRT and the DSST remained significant (hazard ratio1-point DWRT score increment = 0.90, 95% confidence interval: 0.84, 0.97; hazard ratio 7-point DSST score increment = 0.86, 95% confidence interval: 0.80, 0.93). Cognitive function measured in middle age appears to have prognostic importance for life expectancy similar to that reported in elderly adults.     

Prospective association between hormone replacement therapy,heart rate,and heart rate variability. The Atherosclerosis risk in communities study

Hormone replacement therapy is universally associated with coronary heart disease (CHD) in observational studies, but it is unknown whether this association is mediated by the autonomic nervous system. We tested the hypothesis that postmenopausal hormone replacement therapy was associated with more favorable heart rate (HR) and heart rate variability (HRV) in a population sample of women (n=2,621). Hormone therapy use was measured at four examinations beginning in 1987. Supine HR and HRV indices were measured for 6 minutes at the final examination (1996-1998). In unadjusted linear regression models, hormone therapy was associated with lower HR (hormone use=64.7 vs. never=65.7 beats/min, P=.01) and higher HRV. However, following adjustment for age and CHD risk factors, both associations were eliminated. Results from this observational study suggest that hormone therapy is not associated with HR or HRV. These analyses should be replicated in a randomized trial.     

雌激素替代治疗对大鼠动脉粥样硬化的影响

目的:了解早期经皮雌激素替代治疗(estrogen replacement therapy,ERT)对高脂喂养的去势雌性大鼠动脉粥样硬化水平的影响。方法:28只大鼠随机分为4组:A组为假手术对照组,B组为单纯去势组,C组为去势+小剂量ERT组,D组为去势+大剂量ERT组。4组小鼠均给予高脂饮食12周,分别于术前、高脂喂食4周和12周后抽血测定血脂、雌二醇含量及血清SOD活力。结果:12周后B组小鼠血清雌二醇含量明显低于A组(P<0.05),D组明显高于A组(P<0.05),C组与A组间比较差异无统计学意义(P>0.05);12周后B组小鼠血清TC、LDL-C水平显著高于A组(P<0.05);C、D组小鼠的血清TC、LDL-C水平均低于A组(P<0.05),而B组的TG、HDL-C水平均低于其余3组。B组主动脉粥样斑块面积明显大于A、C及D组(P<0.05),C、D两组的斑块面积小于A组(P<0.05);B组血清SOD活力明显下降。结论:早期ERT可改善血脂代谢,抑制血清SOD活性的下降,从而抑制大鼠动脉粥样硬化形成。     

Baldness and myocardial infarction in men: the atherosclerosis risk in communities study

Because hair loss may be a surrogate measure of androgenic activity-possibly a determinant of coronary atherosclerosis-several studies have explored the presence and magnitude of an association between male pattern baldness and myocardial infarction (MI). In particular, vertex baldness, but not frontal baldness alone, was strongly associated with incident MI in a large, hospital-based, case-control study. The authors examined these associations in a cross-sectional sample of 5,056 men aged 52-75 years, of whom 767 had a history of MI. The sample was derived from the Atherosclerosis Risk in Communities (ARIC) Study (1987-1998). As compared with a baldness-free reference group, the estimated odds ratios for prevalent MI from a multivariable model were 1.28 (frontal baldness), 1.02 (mild vertex baldness), 1.40 (moderate vertex baldness), and 1.18 (severe vertex baldness). Other regression models have yielded similar results, including the absence of a monotonic "dose-response relation" between the extent of vertex baldness and prevalent MI. The authors also examined the relation of baldness pattern to carotid intimal-medial thickness, a measure of atherosclerosis, among those who were free of clinical cardiovascular disease. The estimated mean differences in carotid intimal-medial thickness between groups of men with various types of baldness and their baldness-free counterparts were all close to zero. The results of this study suggest that male pattern baldness is not a surrogate measure of an important risk factor for myocardial infarction or asymptomatic atherosclerosis.     

Endogenous postmenopausal hormones and carotid atherosclerosis: a case-control study of the atherosclerosis risk in communities cohort

Studies examining the relation between endogenous postmenopausal hormone levels and cardiovascular disease have yielded conflicting results. After excluding women with a history of hormone replacement therapy (HRT) use, the authors conducted a US case-control study in 1987-1992 comparing endogenous postmenopausal hormone levels in women with and without significant carotid atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) cohort. Atherosclerosis was assessed by using B-mode ultrasound to measure carotid artery intimal-medial thickness (IMT). Cases (n = 182) were postmenopausal women with average IMT measurements greater-than-or-equal the 95th percentile. Controls (n = 182) were frequency matched to cases on age and ARIC center and had IMT measurements < the 75th percentile. After adjustment for cardiovascular risk factors, no association was found between the odds of atherosclerosis and increasing quartiles of estrone, dehydroepiandrosterone sulfate, or androstenedione. Compared with participants in the lowest quartile of sex hormone-binding globulin (SHBG), those in the highest quartile had a significantly lower odds of atherosclerosis (odds ratio = 0.48, 95% confidence interval: 0.24, 0.97). Similarly, participants in the highest quartile of total testosterone had a lower odds of atherosclerosis (odds ratio = 0.38, 95% confidence interval: 0.20, 0.74). The authors found higher total testosterone and SHBG to be inversely related to carotid atherosclerosis, suggesting their potential importance in reducing atherosclerotic risk in postmenopausal women not using HRT.     

Occupational physical activity in the atherosclerosis risk in communities study

PURPOSE: Accumulation of physical activity throughout the day is recommended to reduce health risks and enhance quality of life. Yet, many epidemiologic studies measure leisure activity only, without assessment of occupational activity. The purposes of this study were to describe occupational activity and to quantify the association between occupational and leisure activity in 2991 African American and 8566 White middle-aged adults. METHODS: Physical activity was measured by the Baecke questionnaire in 1987-89 for participants 45 to 64 years of age in the Atherosclerosis Risk in Communities Study. RESULTS: Reported occupational activity was greater among African American men and women compared to White men and women. Leisure activity was greater among White men and women compared to African American men and women. Work indices (range-1 (low) to 5 (high)) were highest among African American women (2.78) and men (2.72), followed by White men (2.55) and women (2.45), adjusted for age, study center, body mass index, and perceived health status. Those with the highest occupational activity had lower participation in any sport or exercise than those with lower occupational activity across race-gender groups. CONCLUSIONS: This data suggests that studies relying solely on leisure activity may miss important information provided by occupational physical activity.     

Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study

Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the Atherosclerosis Risk in Communities Study (1990-1998), who were followed between 3 and 6 years. Alcohol consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of various levels. Incident diabetes was determined by blood glucose measurements and self-report. After adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21 drinks/week when compared with men who drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were current drinkers but reported no regular use of spirits, beer, or wine were 1.82 (95% confidence interval: 1.14, 2.92). Results of this study support the hypothesis that high alcohol intake increases diabetes risk among middle-aged men. However, more moderate levels of alcohol consumption do not increase risk of type 2 diabetes in either middle-aged men or women.     

The relationship between temporal changes in blood pressure and changes in cognitive function: atherosclerosis risk in communities (ARIC) study

BACKGROUND: Although previous epidemiological studies have reported that hypertension is a major risk factor for decline in brain perfusion and atrophy, which are known to be related to cognitive decline, the impact of temporal changes in blood pressure on age-related cognitive declines has not been assessed. METHODS: The present study evaluates changes in blood pressure and cognitive decline over a 6-year period in the Atherosclerosis Risk in Communities (ARIC) Study. This report is based on 8,058 men and women aged 48-67 years examined in the second (1990-92), and fourth (1996-98) ARIC cohort visits. Changes between these visits were measured in hypertension status and three cognitive function tests: Delayed Word Recall (DWR), the Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF). Adjusted mean differences in cognitive function were compared among five categories of hypertension status by using linear regression modeling. RESULTS: In the present study, older subjects with uncontrolled hypertension had a significantly larger mean DSS/WAIS-R score decline than normotensive subjects. Although other cognitive declines did not achieve statistical significance, both cross-sectional and change analysis suggested that partially controlled or uncontrolled hypertension is associated with a less favorable cognitive profile, particularly when considering results of the DSS and the WF tests. CONCLUSIONS: The present study results provide some support to the hypothesis that hypertension status changes over 6 years in individuals initially aged 48-67 years are related to cognitive changes.     

A meta-analysis of estrogen replacement therapy and risk of epithelial ovarian cancer

Estrogen replacement therapy (ERT) has not been associated with epithelial ovarian cancer in most reported epidemiologic studies that have looked for an association. Some studies may have found weak statistically nonsignificant associations because the number of cases or number of women who reported estrogen use was small. We performed a meta-analysis of data from 15 case-control studies that provided data on ERT and risk of epithelial ovarian cancer. The 15 combined studies were statistically heterogeneous (chi(2) (14) = 26. 3, P < 0.05) in terms of the effect they found. When we combined these studies using a random effects model, we did not find a significant association of ERT with ovarian cancer (odds ratio = 1.1, 95% confidence interval = 0.9-1.3). There was no clear evidence of a dose-response relation with increasing duration of estrogen use in a subset of five studies that reported estrogen use by duration (overall slope = 0.0012, 95% confidence interval = -0.0055 to 0. 0080). The influences of statistical outliers, study design (hospital or clinic controls vs. community controls), and location (U.S. and Canada vs. Europe and Australia) were examined. The odds ratio was 1.3 (95% confidence interval = 1.0-1.6) in the relatively homogeneous subset of four U.S. case-control studies with community controls, but we cannot rule out the possibility of uncontrolled confounding. The odds ratios for estrogen use for other subgroups defined by geographic location and type of control group were not significantly different from one.     

Influence of retirement on leisure-time physical activity: the atherosclerosis risk in communities study

Cross-sectional data suggest that leisure-time physical activity may increase during retirement. Prospective population-based studies are necessary to characterize leisure activity patterns through retirement among the same persons to verify this observation. Therefore, the purpose of this study was to describe the influence of retirement on leisure activity using data from Atherosclerosis Risk in Communities Study cohort participants aged 45-64 years at baseline. Physical activity was measured by the Baecke questionnaire in 1,825 African-American and 5,957 White participants who were working at the initial visit (1986-1989) and either retired or working 6 years later (1993-1995). Participants who retired during follow-up were more likely to increase their sport participation and television watching than those who continued to work over the 6-year period. Among those reporting sport or exercise at baseline, those retiring over follow-up were more likely to maintain their sport and exercise participation than those who continued to work across race-gender groups. Among those not reporting sport or exercise at baseline, those who retired were more likely to adopt activity than those who continued to work except for African-American women. In this study, retirement was associated with gains in sport and exercise participation as well as television watching.     

Hyperhomocyst(e)inemia and hemostatic factors: the atherosclerosis risk in communities study

PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to hemostatic factors in a population-based sample without evidence of cardiovascular disease. METHODS: A subsample of 660 participants--67 African-American women, 53 African-American men, 201 white women, and 339 white men--was selected from the Atherosclerosis Risk in Communities Study baseline cohort. This was based on carotid intimal-medial wall thickness above the 90th percentile or below the 75th percentile of the population distribution, assessed by B-mode ultrasonography. Unadjusted and multivariable-adjusted associations between fasting plasma H(e) and the hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C antigen, hematocrit, platelet count, beta-thromboglobulin (beta-TG), tissue plasminogen activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined. RESULTS: Mean age-adjusted H(e) was positively, albeit weakly, correlated with beta-TG, tPA, hematocrit, D-dimer and PAI-1; inversely correlated with protein C; and was higher in smokers, men and African-Americans. In multivariable regression, beta-TG, tPA, and factor VII:c were positively associated with H(e), as well as age, black race, male sex, and current cigarette smoking. CONCLUSIONS: These cross-sectional data for a biracial group of middle-aged individuals suggest that H(e) levels falling below values consistent with homocyst(e)inemia are associated with several prothrombotic factors after adjustment for sociodemographic factors. If H(e) change is antecedent to altered hemostasis, FDA-mandated fortification of grain products with folic acid for prevention of fetal neural tube defects may lead to both reduced plasma H(e) levels and improved hemostatic profiles.     

Supermarkets, other food stores, and obesity: the atherosclerosis risk in communities study

BACKGROUND: Obesity is a leading public health concern, and although environmental factors have been hypothesized to play a role in the prevention of obesity, little empirical data exist to document their effects. The purpose of this study was to examine whether characteristics of the local food environment are associated with the prevalence of cardiovascular disease risk factors. METHODS: A cross-sectional study of men and women participating in the third visit (1993-1995) of the Atherosclerosis Risk in Communities (ARIC) Study was conducted in 2004. The analyses included 10,763 ARIC participants residing in one of the 207 eligible census tracts located in the four ARIC-defined geographic areas. Names and addresses of food stores located in Mississippi, North Carolina, Maryland, and Minnesota were obtained from departments of agriculture. Multilevel modeling was used to calculate prevalence ratios of the associations between the presence of specific types of food stores and cardiovascular disease risk factors. RESULTS: The presence of supermarkets was associated with a lower prevalence of obesity and overweight (obesity prevalence ratio [PR] = 0.83, 95% confidence interval [CI] = 0.75-0.92; overweight PR = 0.94, 95% CI = 0.90-0.98), and the presence of convenience stores was associated with a higher prevalence of obesity and overweight (obesity PR = 1.16, 95% CI = 1.05-1.27; overweight PR = 1.06, 95% CI = 1.02-1.10). Associations for diabetes, high serum cholesterol, and hypertension were not consistently observed. CONCLUSIONS: Results from this study suggest that characteristics of local food environments may play a role in the prevention of overweight and obesity.     

Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis risk in communities study

The authors examined the association of breast cancer incidence with serum levels of insulin and glucose in a cohort of 7,894 women aged 45-64 years from four US communities. Anthropometric factors and fasting levels of insulin and glucose were measured at baseline (1987-1989). Over an average follow-up period of 7.1 years (1987-1995), 187 breast cancer cases were ascertained. Breast cancer was associated positively with body mass index but not with waist:hip ratio or serum insulin level. After adjustment for age, race, and study site, the incidence of breast cancer was 60% higher among diabetic women than among women with fasting glucose levels under 100 mg/dl, but this association was attenuated after further adjustment for body mass index and other covariates (adjusted rate ratio = 1.39, 95% confidence interval: 0.86, 2.23). Circulating insulin levels were not predictive of future breast cancer incidence, but there may be a weak association with type 2 diabetes, perhaps modulated via increased adiposity.     

Coffee and sweetened beverage consumption and the risk of type 2 diabetes mellitus: the atherosclerosis risk in communities study

The authors analyzed data from a prospective, community-based cohort to assess the risk of incident type 2 diabetes mellitus associated with coffee and sweetened beverage consumption. They included 12,204 nondiabetic, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1999). Consumption of each beverage was assessed by food frequency questionnaire and classified into categories of cups per day. They found an inverse association, after adjusting for potential confounders, between increased coffee consumption and risk of type 2 diabetes mellitus in men (for > or =4 cups (> or =0.95 liter)/day compared with almost never: hazard ratio = 0.77, p(trend) = 0.02) with no significant association in women (hazard ratio = 0.89, p(trend) = 0.32) using a combination of self-report of physician-diagnosed diabetes, diabetes treatment, and a fasting or nonfasting blood glucose test. When self-reported diabetes or diabetes treatment alone was used, a stronger and significant inverse association was seen in men and women. Sweetened beverage consumption (men: hazard ratio = 1.03, p(trend) = 0.94; women: hazard ratio = 1.01, p(trend) = 0.58) showed no consistent association with the incidence of type 2 diabetes mellitus. In summary, increased coffee consumption was significantly associated with a decreased risk of diagnosed type 2 diabetes mellitus in community-based US adults.