Segment-specific association between plasma homocysteine level and carotid artery intima-media thickness in the Framingham Offspring Study.

Elevated plasma total homocysteine (tHcy) level is an established risk factor for cardiovascular disease. The relationship between tHcy and carotid artery intima-media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT had not been systematically studied, however. Because the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action. We examined the cross-sectional segment-specific relationships of tHcy to ICA/bulb-IMT and CCA-IMT in 2499 participants from the Framingham Offspring Study who were free of cardiovascular disease. In multivariate linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared with the other quartile categories, in both the age- and sex-adjusted and the multivariate-adjusted models (P for trend <.0001 and <.01, respectively). We observed a significant age-by-tHcy interaction for ICA/bulb-IMT (P=.03) and thus stratified the analyses by median age (58 years). A significant positive trend between tHcy and ICA/bulb-IMT was seen in individuals age ≥58 years (P for trend <.01), but not in younger individuals (P for trend=.24) in multivariate-adjusted models. For CCA-IMT, no significant trends were observed in any of the analyses. The segment-specific association between elevated tHcy level and ICA/bulb-IMT suggests an association between tHcy and plaque formation.

Advance care planning and health care preferences of community-dwelling elders: the Framingham Heart Study.

OBJECTIVE: The study objective was to describe self-reported advance care planning, health care preferences, use of advance directives, and health perceptions in a very elderly community-dwelling sample. METHODS: We interviewed surviving participants of the original cohort of the Framingham Heart Study who were cognitively intact and attended a routine research examination between February 2004 and October 2005. Participants were queried about discussions about end-of-life care, preferences for care, documentation of advance directives, and health perceptions. RESULTS: Among 220 community-dwelling respondents, 67% were women with a mean age of 88 years (range 84-100 years). Overall, 69% discussed their wishes for medical care at the end of life with someone, but only 17% discussed their wishes with a physician or health care provider. Two thirds had a health care proxy, 55% had a living will, and 41% had both. Most (80%) respondents preferred comfort care over life-extending care, and 71% preferred to die at home; however, substantially fewer respondents said they would rather die than receive specific life-prolonging interventions (chronic ventilator [63%] or feeding tube [64%]). Many were willing to endure distressing health states, with fewer than half indicating that they would rather die than live out their life in a great deal of pain (46%) or be confused and/or forgetful (45%) all of the time. CONCLUSIONS: Although the vast majority of very elderly community-dwellers in this sample appear to prefer comfort measures at the end of life, many said they were willing to endure specific life-prolonging interventions and distressing health states to avoid death. Our results highlight the need for physicians to better understand patients' preferences and goals of care to help them make informed decisions at the end of life.

Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study.

OBJECTIVE: To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP). METHODS AND RESULTS: In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22). CONCLUSIONS: An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.

Characteristics of Framingham offspring participants with long-lived parents.

BACKGROUND: Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Incidence and prognosis of syncope.

BACKGROUND: Little is known about the epidemiology and prognosis of syncope in the general population. METHODS: We evaluated the incidence, specific causes, and prognosis of syncope among women and men participating in the Framingham Heart Study from 1971 to 1998. RESULTS: Of 7814 study participants followed for an average of 17 years, 822 reported syncope. The incidence of a first report of syncope was 6.2 per 1000 person-years. The most frequently identified causes were vasovagal (21.2 percent), cardiac (9.5 percent), and orthostatic (9.4 percent); for 36.6 percent the cause was unknown. The multivariable-adjusted hazard ratios among participants with syncope from any cause, as compared with those who did not have syncope, were 1.31 (95 percent confidence interval, 1.14 to 1.51) for death from any cause, 1.27 (95 percent confidence interval, 0.99 to 1.64) for myocardial infarction or death from coronary heart disease, and 1.06 (95 percent confidence interval, 0.77 to 1.45) for fatal or nonfatal stroke. The corresponding hazard ratios among participants with cardiac syncope were 2.01 (95 percent confidence interval, 1.48 to 2.73), 2.66 (95 percent confidence interval, 1.69 to 4.19), and 2.01 (95 percent confidence interval, 1.06 to 3.80). Participants with syncope of unknown cause and those with neurologic syncope had increased risks of death from any cause, with multivariable-adjusted hazard ratios of 1.32 (95 percent confidence interval, 1.09 to 1.60) and 1.54 (95 percent confidence interval, 1.12 to 2.12), respectively. There was no increased risk of cardiovascular morbidity or mortality associated with vasovagal (including orthostatic and medication-related) syncope. CONCLUSIONS: Persons with cardiac syncope are at increased risk for death from any cause and cardiovascular events, and persons with syncope of unknown cause are at increased risk for death from any cause. Vasovagal syncope appears to have a benign prognosis.

Obesity and the risk of heart failure.

BACKGROUND: Extreme obesity is recognized to be a risk factor for heart failure. It is unclear whether overweight and lesser degrees of obesity also pose a risk. METHODS: We investigated the relation between the body-mass index (the weight in kilograms divided by the square of the height in meters) and the incidence of heart failure among 5881 participants in the Framingham Heart Study (mean age, 55 years; 54 percent women). With the use of Cox proportional-hazards models, the body-mass index was evaluated both as a continuous variable and as a categorical variable (normal, 18.5 to 24.9; overweight, 25.0 to 29.9; and obese, 30.0 or more). RESULTS: During follow-up (mean, 14 years), heart failure developed in 496 subjects (258 women and 238 men). After adjustment for established risk factors, there was an increase in the risk of heart failure of 5 percent for men and 7 percent for women for each increment of 1 in body-mass index. As compared with subjects with a normal body-mass index, obese subjects had a doubling of the risk of heart failure. For women, the hazard ratio was 2.12 (95 percent confidence interval, 1.51 to 2.97); for men, the hazard ratio was 1.90 (95 percent confidence interval, 1.30 to 2.79). A graded increase in the risk of heart failure was observed across categories of body-mass index. The hazard ratios per increase in category were 1.46 in women (95 percent confidence interval, 1.23 to 1.72) and 1.37 in men (95 percent confidence interval, 1.13 to 1.67). CONCLUSIONS: In our large, community-based sample, increased body-mass index was associated with an increased risk of heart failure. Given the high prevalence of obesity in the United States, strategies to promote optimal body weight may reduce the population burden of heart failure.

Serum aldosterone and the incidence of hypertension in nonhypertensive persons.

BACKGROUND: Primary hyperaldosteronism is a well-recognized cause of secondary hypertension. It is unknown whether serum aldosterone levels within the physiologic range influence the risk of hypertension. METHODS: We investigated the relation of baseline serum aldosterone levels to increases in blood pressure and the incidence of hypertension after four years in 1688 nonhypertensive participants in the Framingham Offspring Study (mean age, 55 years), 58 percent of whom were women. We defined an increase in blood pressure as an increment of at least one blood-pressure category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and defined hypertension as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications. RESULTS: At follow-up, the blood-pressure category had increased in 33.6 percent of the participants, and hypertension had developed in 14.8 percent. In multivariable models, a 16 percent increase in the risk of an elevation in blood pressure (P=0.002) and a 17 percent increase in the risk of hypertension (P=0.03) were observed per quartile increment in the serum aldosterone level. The highest serum aldosterone quartile, relative to the lowest, was associated with a 1.60-fold risk of an elevation in blood pressure (95 percent confidence interval, 1.19 to 2.14) and a 1.61-fold risk of hypertension (95 percent confidence interval, 1.05 to 2.46). The associations between the serum aldosterone level and blood-pressure outcomes were not significantly affected by adjustment for urinary sodium excretion or left ventricular thickness or internal dimensions. CONCLUSIONS: In our community-based sample, increased aldosterone levels within the physiologic range predisposed persons to the development of hypertension.

Low-grade albuminuria and the risks of hypertension and blood pressure progression.

BACKGROUND: It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively. METHODS AND RESULTS: We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximately 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03). CONCLUSIONS: Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension.

Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study.

BACKGROUND: Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. METHODS AND RESULTS: We examined the association of urinary albumin excretion (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49 (19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD (hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (> or =3.9 microg/mg for men, > or =7.5 microg/mg for women) experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P<0.001) and a borderline significantly increased risk of death (adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P=0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest probabilities of CVD. CONCLUSIONS: In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR <30 microg/mg indicates "normal" albumin excretion.

Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study.

BACKGROUND: Throughout the past 50 years, heart disease has been the leading cause of death in the United States. Although declines in coronary heart disease (CHD) mortality have been noted, there is still uncertainty about the magnitude of the decline and whether the trend is similar for sudden cardiac death (SCD). METHODS AND RESULTS: We examined temporal trends in SCD and nonsudden CHD death in the Framingham Heart Study original and offspring cohorts from 1950 to 1999. SCD was defined as a death attributed to CHD with preceding symptoms that lasted less than 1 hour; all deaths were adjudicated by a physician panel. Log-linear Poisson regression was used to estimate CHD mortality and SCD risk ratios (RRs); RRs were adjusted for age and gender. There were 811 CHD deaths: 453 nonsudden and 358 SCDs. Ninety-one (20%) of nonsudden CHD deaths and 173 (48%) of SCDs were in subjects free of antecedent CHD. From 1950-1969 to 1990-1999, overall CHD death rates decreased by 59% (95% CI 47% to 68%, P(trend)<0.001). Nonsudden CHD death decreased by 64% (95% CI 50% to 74%, P(trend)<0.001), and SCD rates decreased by 49% (95% CI 28% to 64%, P(trend)<0.001). These trends were seen in men and women, in subjects with and without a prior history of CHD, and in smokers and nonsmokers. CONCLUSIONS: The risks of SCD and nonsudden CHD mortality have decreased by 49% to 64% over the past 50 years. These trends were evident in subjects with and without heart disease, which suggests important contributions of primary and secondary prevention to the decreasing risk of CHD death and SCD.

Natural history of asymptomatic left ventricular systolic dysfunction in the community.

BACKGROUND: Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community. METHODS AND RESULTS: We studied 4257 participants (1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD (visually estimated ejection fraction [EF]50%, n=4128) and ALVD (n=129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 (CI 3.1 to 13.5). Mild ALVD (EF 40% to 50%, n=78) and moderate-to-severe ALVD (EF <40%, n=51) were associated with adjusted HRs for CHF of 3.3 (CI 1.7 to 6.6) and 7.8 (CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk (adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years. CONCLUSIONS: Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD.

Clinical correlates and prognostic significance of exercise-induced ventricular premature beats in the community: the Framingham Heart Study.

BACKGROUND: Recent investigations suggest that ventricular premature beats during exercise (EVPBs) are associated with increased cardiovascular mortality in asymptomatic individuals, but mechanisms underlying the association are unclear. METHOD AND RESULTS: We evaluated 2885 Framingham Offspring Study participants (1397 men; mean age, 43 years) who were free of cardiovascular disease and who underwent a routine exercise stress test; 792 participants (27%) had development of EVPBs (median, 0.22/min of exercise). Logistic regression was used to evaluate predictors of EVPBs. Cox models were used to examine the relations of infrequent (less than or equal to median) and frequent (greater than median) versus no EVPBs to incidence of hard coronary heart disease (CHD) event (recognized myocardial infarction, coronary insufficiency, or CHD death) and all-cause mortality, adjusting for vascular risk factors and exercise variables. Age and male sex were key correlates of EVPBs. During follow-up (mean, 15 years), 142 (113 men) had a first hard CHD event and 171 participants (109 men) died. EVPBs were not associated with hard CHD events but were associated with increased all-cause mortality rates (multivariable-adjusted hazards ratio, 1.86, 95% CI, 1.24 to 2.79 for infrequent, and 1.71, 95% CI, 1.18 to 2.49 for frequent EVPBs versus none). The relations of EVPBs to mortality risk were not influenced by VPB grade, presence of recovery VPBs, left ventricular dysfunction, or an ischemic ST-segment response. CONCLUSIONS: In our large, community-based sample of asymptomatic individuals, EVPBs were associated with increased risk of death at a much lower threshold than previously reported. Additional studies are needed to confirm these findings and to clarify the underlying mechanisms.

Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study.

BACKGROUND: Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. METHODS AND RESULTS: We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD > or =90th percentile, n=204) and increased LVWT (LVWT > or =90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass). CONCLUSIONS: In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study.

OBJECTIVES: We sought to determine whether seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) is an independent predictor of incident cardiovascular disease. BACKGROUND: Recent reports have suggested that infections may contribute to risk of cardiovascular disease. However, prospective studies of these associations in a free-living population are lacking. METHODS: We measured serum H. pylori IgG, C. pneumoniae IgG and IgA, and CMV IgG levels in Framingham Heart Study cohort participants. Blood samples were drawn during the 16th biennial examination cycle (1979 to 1982) from 1,187 participants free of cardiovascular disease (mean age 69 years) and stored at -20 degrees C. A pooled primary end point of myocardial infarction, atherothrombotic stroke, and coronary heart disease deaths was studied in relation to serology. Using a Cox model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender, and established risk factors. RESULTS: Seropositivity to H. pylori IgG, C. pneumoniae IgG, C. pneumoniae IgA, and CMV IgG was 60%, 45%, 11%, and 69%, respectively. During 10 years of follow-up, incident cardiovascular disease occurred in 199 participants (16.8%). In age- and gender-adjusted models, H. pylori IgG (HR 1.09, 95% CI 0.81 to 1.46), C. pneumoniae IgG (HR 0.91, 95% CI 0.68 to 1.20), C. pneumoniae IgA (HR 0.65, 95% CI 0.39 to 1.07), and CMV IgG (HR 0.84, 95% CI 0.62 to 1.12) were not associated with incident cardiovascular disease. These associations were further attenuated after adjustment for risk factors including body mass index, total and high-density lipoprotein cholesterol, diabetes mellitus, smoking, and hypertension. These estimates did not change for the individual components of cardiovascular disease, and seropositivity to more than one organism did not alter these risk estimates substantially. CONCLUSIONS: In this elderly cohort, chronic H. pylori, C. pneumoniae, and CMV infections, as evidenced by seropositivity, were not associated with increased risk for cardiovascular disease. Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons.

Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study.

OBJECTIVE: The aim of this study was to examine the echocardiographic features and associations of mitral valve prolapse (MVP) diagnosed by current two-dimensional echocardiographic criteria in an unselected outpatient sample. BACKGROUND: Previous studies of patients with MVP have emphasized the frequent occurrence of echocardiographic abnormalities such as significant mitral regurgitation (MR) and left atrial (LA) enlargement that are associated with clinical complications. These studies, however, have been limited by the use of hospital-based or referral series. METHODS: We quantitatively studied all 150 subjects with possible MVP by echocardiography and 150 age- and gender-matched subjects without MVP from the 3,491 subjects in the Framingham Heart Study. Based on leaflet morphology, subjects were classified as having classic (n = 46), nonclassic (n = 37), or no MVP. RESULTS: Leaflet length, MR degree, and LA and left ventricular size were significantly but mildly increased in MVP (p < 0.0001 to 0.004), with mean values typically within normal range. Average MR jet area was 15.1 +/- 1.4% (mild) in classic MVP and 8.9 +/- 1.5% (trace) in nonclassic MVP; MR was severe in only 3 of 46 (6.5%) subjects with classic MVP, and LA volume was increased in only 8.7% of those with classic MVP and 2.7% of those with nonclassic MVP. CONCLUSIONS: Although the echocardiographic characteristics of subjects with MVP in the Framingham Heart Study differ from those without MVP, they display a far more benign profile of associated valvular, atrial, and ventricular abnormalities than previously reported in hospital- or referral-based series. Therefore, these findings may influence the perception of and approach to the outpatient with MVP.

A comparison of death certificate out-of-hospital coronary heart disease death with physician-adjudicated sudden cardiac death.

The number of deaths due to out-of-hospital coronary heart disease as determined by death certificates was compared with the number physician-adjudicated sudden cardiac deaths in the Framingham Heart Study from 1950 to 1999. Out-of-hospital coronary heart disease deaths overestimated sudden cardiac death by 47%, suggesting that out-of-hospital coronary heart disease death rates derived from death certificates should be interpreted with caution.

Depressive symptoms, coronary heart disease, and overall mortality in the Framingham Heart Study.

OBJECTIVE: Although a substantial number of studies have shown that depressive symptoms predict worse cardiac outcome for patients with existing coronary disease, relatively few methodologically rigorous studies have examined the relation of depressive symptoms to coronary disease incidence in individuals initially free of heart disease in the community. METHODS: Using multivariable-adjusted sex-stratified Cox proportional hazards regression, we examined the association between depressive symptoms and incident coronary disease and all-cause mortality in 3634 Framingham Heart Study original and offspring cohort participants (mean age 52 years, 55% women) attending a routine study examination between 1983 and 1994. RESULTS: Over 6 years of follow-up, 83 participants had a hard coronary heart disease event (myocardial infarction or coronary death), and 133 died. Depressive symptoms (Center for Epidemiologic Studies Depression Scale (CES-D) > or =16) did not predict hard coronary disease events. All-cause mortality, however, was directly associated with depressive symptoms. Compared with the lowest tertile of CES-D score, multivariable-adjusted risks of death in the second and third tertiles were 33% and 88% higher, respectively (hazards ratio per tertile increment = 1.37, 95% confidence interval 1.10-1.71, p for trend = 0.005). CONCLUSION: These findings underscore the importance of further research into the pathogenesis and prevention of excess mortality experienced with depressive symptoms.

The ankle-brachial index in the elderly and risk of stroke, coronary disease, and death: the Framingham Study.

BACKGROUND: A low ankle-brachial index (ABI) is associated with an increased risk of death and cardiovascular disease. Limited data exist regarding the relation between a low ABI and stroke. We sought to examine the relation between a low ABI and stroke, coronary heart disease, and death in the elderly. METHODS: We examined 251 men and 423 women with a mean age of 80 years who had a Framingham Study examination from 1994 to 1995. A low ABI was defined as less than 0.9. Persons were followed up for 4 years for occurrence of stroke or transient ischemic attack, coronary disease, and death. Cox proportional hazards models were used to assess the relation between a low ABI and each outcome after adjusting for age, sex, and prevalent cardiovascular disease. RESULTS: A low ABI was detected in 20% of our sample. Only 18% of the participants with a low ABI reported claudication symptoms. One third of those with a normal ABI and 55% of those with a low ABI had cardiovascular disease at baseline. Results of multivariable Cox proportional hazards analysis demonstrated a statistically significant increase in the risk of stroke or transient ischemic attack in persons with a low ABI (hazards ratio, 2.0; 95% confidence interval, 1.1-3.7). No significant relation between a low ABI and coronary heart disease (hazards ratio, 1.2; 95% confidence interval, 0.7-2.1) or death (hazards ratio, 1.4; 95% confidence interval, 0.9-2.1) was observed. CONCLUSIONS: A low ABI is associated with risk of stroke or transient ischemic attack in the elderly. These results need to be confirmed in larger studies.

Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study.

BACKGROUND: Although excessive alcohol consumption can promote cardiomyopathy, little is known about the association between alcohol consumption and risk for congestive heart failure in the community. OBJECTIVE: To determine the relation between alcohol consumption and risk for congestive heart failure in the community. DESIGN: Community-based, prospective observational study. SETTING: Framingham, Massachusetts. PARTICIPANTS: Participants in the Framingham Heart Study who were free of congestive heart failure and coronary heart disease. MEASUREMENTS: Self-reported alcohol consumption; sex-specific rates of congestive heart failure per 1000 person-years of follow-up by level of alcohol consumption. RESULTS: In men, 99 cases of congestive heart failure occurred during 26 035 person-years of follow-up. In women, 120 cases of congestive heart failure occurred during 35 563 person-years of follow-up. After adjustment for multiple confounders, risk for congestive heart failure was lower among men at all levels of alcohol consumption compared with men who consumed less than 1 drink/wk. The hazard ratio for congestive heart failure was lowest among men who consumed 8 to 14 drinks/wk (0.41 [95% CI, 0.21 to 0.81]) compared with those who consumed less than 1 drink/wk. In women, the age-adjusted hazard ratio for congestive heart failure was lowest among those who consumed 3 to 7 drinks/wk (0.49 [CI, 0.25 to 0.96]) compared with those who consumed less than 1 drink/wk. However, after adjustment for multiple predictors of congestive heart failure, this association was no longer statistically significant. CONCLUSIONS: In the community, alcohol consumption is not associated with increased risk for congestive heart failure, even among heavy drinkers (> or = 15 drinks/wk in men and > or = 8 drinks/wk in women). To the contrary, when consumed in moderation, alcohol appears to protect against congestive heart failure.

Hypertension in adults across the age spectrum: current outcomes and control in the community.

CONTEXT: Data are sparse regarding current rates of hypertension treatment and control, and risks associated with hypertension, among persons older than 80 years. OBJECTIVE: To determine the prevalence of blood pressure stages, hypertension treatment and control, and cardiovascular risk among older patients with hypertension. DESIGN, SETTING, AND PARTICIPANTS: A community-based cohort study in which data were collected during all Framingham Heart Study examinations attended in the 1990s. Participants were pooled according to age: younger than 60 years, 60 to 79 years, or 80 years or older. There were 5296 participants who contributed 14 458 person-examinations of observation, including 7135 hypertensive person-examinations (4919 treated). MAIN OUTCOME MEASURES: Prevalence of hypertension, its treatment, and its control were compared across age groups. Risks for incident cardiovascular disease during follow-up of up to 6 years were estimated as multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. RESULTS: Prevalence of hypertension and drug treatment increased with advancing age, whereas control rates were markedly lower in older women (systolic <140 and diastolic <90 mm Hg). For ages younger than 60 years, 60 to 79, and 80 years and older, respectively, control rates were 38%, 36%, and 38% in men (P = .30) and 38%, 28%, and 23% in women (P<.001). Relative risks for cardiovascular disease associated with increasing blood pressure stage did not decline with advancing age, and absolute risks increased markedly. Among participants 80 years of age or older, major cardiovascular events occurred in 9.5% of the normal blood pressure (referent) group, 19.8% of the prehypertension group (HR, 1.9; 95% CI, 0.9-3.9), 20.3% of the stage 1 hypertension group (HR, 1.8; 95% CI, 0.8-3.7), and 24.7% of the stage 2 or treated hypertension group (HR, 2.4; 95% CI, 1.2-4.6). CONCLUSIONS: Relative to current national guidelines, rates of blood pressure control in the community are low, especially among older women with hypertension. Short-term risks for cardiovascular disease are substantial, indicating the need for greater efforts at safe, effective risk reduction among the oldest patients with hypertension.