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Background We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups. Methods We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts in the age range 45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study) (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874 [16.2%] were African Americans). The risk algorithm included age, sex, body mass index, systolic blood pressure, electrocardiographic PR interval, hypertension treatment, and heart failure. Results We found 1359 incident AF events in 100 074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years; and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4 cases/1000 person-years). The strongest risk factors in all samples were age and heart failure. The relative risks for incident AF associated with risk factors were comparable across cohorts and race groups. After recalibration for baseline incidence and risk factor distribution, the Framingham algorithm, reported in C statistic, performed reasonably well in all samples: AGES, 0.67 (95% confidence interval [CI], 0.64-0.71); CHS whites, 0.68 (95% CI, 0.66-0.70); and CHS African Americans, 0.66 (95% CI, 0.61-0.71). Risk factors combined in the algorithm explained between 47.0% (AGES) and 63.6% (FHS) of the population-attributable risk. Conclusions Risk of incident AF in community-dwelling whites and African Americans can be assessed reliably by routinely available and potentially modifiable clinical variables. Seven risk factors accounted for up to 64% of risk.

Clinical hypothyroidism and hyperthyroidism are recognized causes of reversible dementia, but previous studies relating thyrotropin levels to cognitive performance in clinically euthyroid persons have yielded inconsistent results.We related serum thyrotropin concentrations measured at baseline (March 1977-November 1979) to the risk of Alzheimer disease (AD) in 1864 cognitively intact, clinically euthyroid Framingham original cohort participants (mean age, 71 years; 59% women). Sex-specific Cox proportional hazards models were constructed using tertiles of thyrotropin concentration (tertile 2 as the referent) and adjusting for age, apolipoprotein E epsilon4 allele status, educational level, plasma homocysteine level, current smoking, body mass index, prevalent stroke, and atrial fibrillation.During a mean follow-up of 12.7 years (range, 1-25 years), 209 participants (142 women) developed AD. Women in the lowest (1.0 mIU/L) and highest (2.1 mIU/L) tertiles of serum thyrotropin concentration were at increased risk for AD (multivariate-adjusted hazard ratio, 2.39 [95% confidence interval, 1.47-3.87] [P.001] and 2.15 [95% confidence interval, 1.31-3.52] [P = .003], respectively) compared with those in the middle tertile. Thyrotropin levels were not related to AD risk in men. Analyses excluding individuals receiving thyroid supplementation did not significantly alter these relationships. In analyses limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, the U-shaped relationship between thyrotropin level and AD risk was maintained in women but not when analyses were limited to those with thyrotropin levels of 0.5 to 5.0 mIU/L.Low and high thyrotropin levels were associated with an increased risk of incident AD in women but not in men.

Background Metabolic syndrome (MetS) has been recognized as a prediabetic constellation of symptoms and an independent risk factor for cardiovascular disease. Methods To evaluate the age-adjusted risk of stroke and population-attributable risk associated with MetS and compare with those of overt type 2 diabetes mellitus (hereinafter, “diabetes”), we determined the prevalence of MetS alone, diabetes alone, and both in 2097 subjects in the Framingham Offspring Study, aged 50 to 81 years and free of stroke. Age-adjusted risk ratios, 10-year incidence, and population-attributable risks of stroke were estimated for men and women with MetS alone, diabetes alone, and both. Results Criteria for MetS were met in 30.3% of men and 24.7% of women. Twenty-four percent of men had MetS alone; 7% had diabetes alone; and 6% had both. Twenty percent of women had MetS alone; 3% had diabetes alone; and 5% had both. Over 14 years of follow-up, 75 men and 55 women developed a first stroke; all but 4 events were ischemic. Relative risk (RR) of stroke in persons with both diabetes and MetS (RR, 3.28; confidence interval [CI], 1.82-5.92) was higher than that for either condition alone (MetS alone: RR, 2.10; CI, 1.37-3.22; diabetes alone: RR, 2.47; CI, 1.31-4.65). The population-attributable risk, owing to its greater prevalence, was greater for MetS alone than for diabetes alone (19% vs 7%), particularly in women (27% vs 5%). Conclusions Metabolic syndrome is more prevalent than diabetes and a significant independent risk factor for stroke in people without diabetes. Prevention and control of MetS and its components are likely to reduce stroke incidence.

Background Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. Methods A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. Results Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. Conclusions Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Background Clinical hypo- and hyperthyroidism are recognized causes of reversible dementia but prior studies relating thyroid stimulating hormone (TSH) levels to cognitive performance in clinically euthyroid persons have yielded inconsistent results.

Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity.We studied 1697 Framingham Heart Study (FHS) offspring members 30 years or older, whose parents (1) participated in the original FHS cohort and (2) achieved age 85 years or died before January 1, 2005. Offspring participants (mean +/- SD age, 40 +/- 7 years; 51% women) were grouped according to whether neither (n = 705), one (n = 804), or both parents (n = 188) survived to 85 years or older. We examined offspring risk factors at examination cycle 1 (1971-1975) including age, sex, education, cigarette smoking, systolic and diastolic blood pressures, total-high-density lipoprotein cholesterol ratio, body mass index, and Framingham Risk Score. Participants returning for examination cycle 3 (1983-1987; n = 1319) were eligible for inclusion in longitudinal analyses evaluating risk factor progression from baseline to a higher follow-up risk category.For all factors studied, except body mass index, we observed statistically significant linear trends for lower offspring examination 1 risk factor levels with increasing parental survival category. The mean Framingham Risk Score was most favorable in offspring with both parents surviving to 85 years or older and was progressively worse in those with one or no long-lived parent (0.55, 1.08, and 1.71, respectively; P value for trend,.001). Longitudinally, offspring of parents who lived longer had lower risk of blood pressure and Framingham Risk Score progression.Our findings suggest that individuals with long-lived parents have advantageous cardiovascular risk profiles in middle age compared with those whose parents died younger. The risk factor advantage persists over time.

Background Previous studies examining the association of plasma cholesterol levels with the risk for development of Alzheimer disease (AD) have been inconclusive. We examined the impact of baseline and lifetime plasma total cholesterol levels averaged across many years on the risk for AD in a large, population-based cohort. Methods Five thousand two hundred nine subjects from the Framingham Study original cohort underwent biennial evaluation for cardiovascular risk factors since 1950, with estimations of serum total cholesterol levels at 19 of these 25 biennial examinations. The study sample consisted of 1026 subjects from this cohort who were alive and free of stroke and dementia at examination cycle 20 (1988-1989) and had undergone apolipoprotein E (APOE) genotyping. The main outcome measure was incident AD diagnosed using standard criteria, according to average total cholesterol levels across biennial examination cycles 1 to 15 and baseline total cholesterol level measured at the 20th biennial examination cycle. Results Alzheimer disease developed in 77 subjects from 1992 to 2000. After adjustment for age, sex,APOEgenotype, smoking, body mass index (calculated as weight in kilograms divided by the square of height in meters), coronary heart disease, and diabetes, we found no significant association between the risk for incident AD and average cholesterol level at biennial examination cycles 1 to 15 (hazard ratio per 10-mg/dL [0.3-mmol/L] rise, 0.95; 95% confidence interval, 0.87-1.04) or baseline total cholesterol level at examination 20 (hazard ratio, 0.97; 95% confidence interval, 0.90-1.05). Conclusion In this large, population-based cohort, baseline and long-term average serum total cholesterol levels were not associated with the risk for incident AD.

Background Elevated fasting total homocysteine (tHcy) levels were recently shown to confer an independent risk for all-cause and cardiovascular disease (CVD) mortality among selected Norwegian patients with confirmed coronary heart disease. We examined whether elevated fasting plasma tHcy levels were predictive of all-cause and CVD mortality in a large, population-based sample of elderly US women and men. Methods Nonfasting plasma tHcy levels were determined in 1933 elderly participants (mean age, 70 ± 7 years; 58.9% women) from the original Framingham Study cohort, examined between 1979 and 1982, with follow-up through 1992. Unadjusted and adjusted (ie, for age, sex, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, and creatinine) relative risk estimates (with 95% confidence intervals [CIs]) for total and CVD mortality were generated by proportional hazards modeling, with tHcy levels (quartiles) as the independent variable. Results There were 653 total deaths and 244 CVD deaths during a median follow-up of 10.0 years. Proportional hazards modeling revealed that tHcy levels of 14.26 µmol/L or greater (the upper quartile), vs less than 14.26 µmol/L (the lower three quartiles), were associated with relative risk estimates of 2.18 (95% CI, 1.86-2.56) and 2.17 (95% CI, 1.68-2.82) for all-cause and CVD mortality, respectively. The relative risk estimates after adjustment for age, sex, systolic blood pressure, diabetes, smoking, and total and high-density lipoprotein cholesterol levels attenuated these associations, but they remained significant: 1.54 (95% CI, 1.31-1.82) for all-cause mortality; 1.52 (95% CI, 1.16-1.98) for CVD mortality. Conclusion Elevated nonfasting plasma tHcy levels are independently associated with increased rates of all-cause and CVD mortality in the elderly.

• Chronic atrial fibrillation without valvular disease has been associated with increased stroke incidence. The impact of atrial fibrillation on the risk of stroke with increasing age was examined in 5184 men and women in the Framingham Heart Study. After 30 years of follow-up, chronic atrial fibrillation appeared in 303 persons. Age-specific incidence rates steadily increased from 0.2 per 1000 for ages 30 to 39 years to 39.0 per 1000 for ages 80 to 89 years. The proportion of strokes associated with this arrhythmia was 14.7%, 68 of the total 462 initial strokes, increasing steadily with age from 6.7% for ages 50 to 59 years to 36.2% for ages 80 to 89 years. In contrast to the impact of cardiac failure, coronary heart disease, and hypertension, which declined with age, atrial fibrillation was a significant contributor to stroke at all ages. ( Arch Intern Med 1987;147:1561-1564)