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Background: Recent reports have indicated that autonomic tone fluctuations measured by heart rate variability (HRV) precede episodes of paroxysmal atrial fibrillation (AF). Little is known about the impact of baseline autonomic tone and the development of new onset AF in a population-based cohort. The purpose of this study was to assess the role of HRV as a predictor of new onset AF.Method: Ambulatory ECG recordings obtained from the Framingham Heart Study subjects attending a routine examination were processed for HRV. The HRV variables analyzed included standard deviation of normal R-R intervals (SDNN), low frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434 women and 1142 men (54 +/- 14.1 years) eligible for the study.Results: In 12 years of follow-up, 65 women and 67 men had new onset AF. The study had 80% power to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in HRV. A one SD decrement in log LF/HF was associated with increased risk of developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06-1.44) in age- and sex-adjusted models; the association was no longer significant (HR = 1.15; 95% CI = 0.98-1.35) after adjusting for potential confounders.Conclusion: Autonomic dysregulation at baseline, as reflected by an altered HRV is associated with risk of AF; however, this association does not persist after adjusting for potential confounders. Much of the apparent association between HRV and AF is mediated by traditional risk factors. [ABSTRACT FROM AUTHOR]

Conflicting findings in the literature have made the relation between job strain and coronary heart disease (CHD) controversial. The effect of high job strain on the 10-year incidence of CHD and total mortality was examined in men and women participating in the Framingham Offspring Study; 3,039 participants, 1,711 men and 1,328 women, aged 18-77 years, were examined between 1984 and 1987 and followed for 10 years. Measures of job strain, occupational characteristics, and risk factors for CHD were collected at the baseline examination. Before and after controlling for systolic blood pressure, body mass index, cigarette smoking, diabetes, and the total/high density lipoprotein cholesterol ratio in Cox proportional hazards models, the authors found that high job strain was not associated with mortality or incident CHD in either men or women over the follow-up period. Contrary to expectation, women with active job strain (high demands-high control) had a 2.8-fold increased risk of CHD (95% confidence interval: 1.1, 7.2) compared with women with high job strain (high demands-low control). For men, higher education, personal income, and occupational prestige were related to decreased risk of total mortality and CHD. These findings do not support high job strain as a significant risk factor for CHD or death in men or women. [ABSTRACT FROM AUTHOR]

Clinical studies have suggested that sleep apnea is associated with impaired brachial artery flow-mediated dilation, a surrogate of endothelial dysfunction. We examined this question among older participants in the baseline examination of the Sleep Heart Health/Cardiovascular Health Study cohort (n = 1,037, age 68 years or older, 56% female). Indices of sleep apnea, derived from 12-channel home polysomnography, were the apnea-hypopnea index (average number of apneas/hypopneas per hour) and the hypoxemia index (percentage of time below 90% O2 saturation). Baseline arterial diameter and percentage of flow-mediated dilation were measured by ultrasound. Sleep apnea measures were associated with baseline diameter and the percentage of flow-mediated dilation, although these associations were weakened after adjustment for other cardiovascular risk factors, particularly body mass index. However, a statistically significant linear association between the hypoxemia index and baseline diameter was observed even after adjustment for body mass index and other confounders (p < 0.01). The associations were stronger among participants who were younger than 80 years and among those who with hypertension. This study adds to the growing body of evidence linking sleep apnea with vascular dysfunction in older subjects. Whether these relationships are entirely independent of obesity is unclear. This association might be one of the mechanisms explaining the relationship between sleep apnea, hypertension, and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: To determine the independent risk factors for atrial fibrillation.Design: Cohort study.Setting: The Framingham Heart Study.Subjects: A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years.Main Outcome Measures: Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease.Results: During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (P < .0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease.Conclusion: In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of echocardiographically determined left ventricular mass (LVM) with incidence of stroke or transient ischemic attack in an elderly cohort.Design: Cohort study with a follow-up period of 8 years.Setting: Population-based sample.Subjects: Elderly original cohort subjects of the Framingham Heart Study who were free of cerebrovascular disease and atrial fibrillation at the 16th biennial examination and who had adequate echocardiograms. This group consisted of 447 men (mean age, 67.8 years; range, 60 to 90 years) and 783 women (mean age, 69.2 years; range 59 to 90 years).Main Outcome Measures: Age-adjusted 8-year incidence of stroke was examined as a function of baseline quartiles of LVM-to-height ratio. Proportional hazards regression was used in multivariate analyses to assess risk of stroke as a function of LVM-to-height ratio quartile, adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and blood lipid levels.Results: Among the 1230 subjects eligible, 89 cerebrovascular disease events (62 strokes and 27 transient ischemic attacks) occurred during follow-up. In men, 8-year age-adjusted incidence of cerebrovascular events was 18.4% in the highest quartile of LVM-to-height ratio and 5.2% in the lowest quartile. Corresponding values in women were 12.2% and 2.9%. The hazard ratio for cerebrovascular events comparing highest to lowest quartile of LVM-to-height ratio was 2.72 (95% confidence interval [CI], 1.39 to 5.36) after adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and the ratio of total cholesterol to high-density lipoprotein cholesterol. After adjusting for age, sex, and cardiovascular disease risk factors, the hazard ratio for cerebrovascular events was 1.45 (95% CI, 1.17 to 1.80) for each quartile increment of LVM-to-height ratio.Conclusions: Echocardiographically determined LVM-to-height ratio offers prognostic information beyond that provided by traditional cerebrovascular disease risk factors. Echocardiography provides information that facilitates identification of individuals at high risk for stroke and transient ischemic attack. [ABSTRACT FROM AUTHOR]

Background: African Americans have an increased incidence and worse prognosis with chronic kidney disease (CKD--estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) than their counterparts of European-descent. Inflammation has been related to renal disease in non-Hispanic whites, but there are limited data on the role of inflammation in renal dysfunction in African Americans in the community.Methods: We examined the cross-sectional relation of log transformed C-reactive protein (CRP) to renal function (eGFR by Modification of Diet and Renal Disease equation) in African American participants of the community-based Jackson Heart Study's first examination (2000 to 2004). We conducted multivariable linear regression relating CRP to eGFR adjusting for age, sex, body mass index, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, hormone replacement therapy, and prevalent cardiovascular disease events. In a secondary analysis we assessed the association of CRP with albuminuria (defined as albumin-to-creatinine ratio > 30 mg/g).Results: Participants (n = 4320, 63.2% women) had a mean age +/- SD of 54.0 +/- 12.8 years. The prevalence of CKD was 5.2% (n = 228 cases). In multivariable regression, CRP concentrations were higher in those with CKD compared to those without CKD (mean CRP 3.2 +/- 1.1 mg/L vs. 2.4 +/- 1.0 mg/L, respectively p < 0.0001). CRP was significantly associated with albuminuria in sex and age adjusted model however not in the multivariable adjusted model (p > 0.05).Conclusion: CRP was associated with CKD however not albuminuria in multivariable-adjusted analyses. The study of inflammation in the progression of renal disease in African Americans merits further investigation. [ABSTRACT FROM AUTHOR]

Background: The association between heart failure in parents and the prevalence of left ventricular systolic dysfunction and the risk of heart failure in their offspring has not been investigated in a community-based setting. Methods: We examined the cross-sectional association of heart failure in parents with the prevalence of left ventricular systolic dysfunction, as well as left ventricular mass, internal dimensions, and wall thickness, in 1497 participants of the Framingham Offspring Study (mean age, 57 years; 819 women) who underwent routine echocardiography. We also investigated prospectively whether heart failure in parents increased the risk of heart failure in 2214 offspring (mean age, 44 years; 1150 women). Results: As compared with the 1039 participants whose parents did not have heart failure, the 458 participants in the cross-sectional cohort who had at least one parent with heart failure were more likely to have increased left ventricular mass (17.0 percent vs. 26.9 percent), left ventricular internal dimensions (18.6 percent vs. 23.4 percent), and left ventricular systolic dysfunction (3.1 percent vs. 5.7 percent); the multivariable-adjusted odds ratios were 1.35 (95 percent confidence interval, 0.99 to 1.84), 1.29 (95 percent confidence interval, 0.96 to 1.72), and 2.37 (95 percent confidence interval, 1.22 to 4.61), respectively. In the longitudinal cohort, heart failure developed in 90 offspring during follow-up (mean length of follow-up, 20 years). The age- and sex-adjusted 10-year incidence rates of heart failure were 2.72 percent among offspring with a parent with heart failure, as compared with 1.62 percent among those without a parent with heart failure. This increase in risk persisted after multivariable adjustment (hazard ratio, 1.70; 95 percent confidence interval, 1.11 to 2.60). Conclusions: Heart failure in parents is associated with an increased prevalence of left ventricular systolic dysfunction cross-sectionally and an elevated risk of heart failure longitudinally. Our data emphasize the contribution of familial factors to the heart-failure burden in the community. [ABSTRACT FROM AUTHOR]

Endothelial function is thought to be an important factor in the pathogenesis of atherosclerosis, hypertension and heart failure. In the 1990s, high-frequency ultrasonographic imaging of the brachial artery to assess endothelium-dependent flow-mediated vasodilation (FMD) was developed. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function. The noninvasive nature of the technique allows repeated measurements over time to study the effectiveness of various interventions that may affect vascular health. However, despite its widespread use, there are technical and interpretive limitations of this technique. State-of-the-art information is presented and insights are provided into the strengths and limitations of high-resolution ultrasonography of the brachial artery to evaluate vasomotor function, with guidelines for its research application in the study of endothelial physiology. [ABSTRACT FROM AUTHOR]

Background: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach.Methods: We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004.Findings: 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously.Interpretation: This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex.Methods: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions.Findings: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted.Interpretation: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Experimental evidence indicates that leptin-deficient animals develop left ventricular (LV) hypertrophy, but data relating circulating leptin levels to cardiac structure and function in subjects >70 years old are lacking. We related circulating leptin concentrations to echocardiographic measurements of cardiac structure and function in 432 participants of the community-based Framingham Heart Study (mean age 75 years, 67% women) who underwent echocardiography at a routine examination (approximately 4 years before leptin concentrations were assayed). In multivariable linear regression, logarithmically transformed gender-standardized leptin concentrations were related to the following echocardiographic measurements: LV mass, left atrial size, and fractional shortening (primary analysis); LV wall thickness and LV end-diastolic dimensions (the 2 components of LV mass); and transmitral early/late diastolic filling velocities (secondary analysis). Leptin concentrations were inversely associated with LV mass, LV wall thickness, and left atrial size (p <0.04 for all). The top gender-specific tertile of leptin was associated with an adjusted LV mass 16 g lower compared with the lowest tertile (p = 0.007 for trend across tertiles). Leptin levels were not associated with LV fractional shortening, transmitral early/late diastolic filling velocities, or LV end-diastolic diameter (p >0.16). In conclusion, our cross-sectional observations suggest a cardioprotective influence of leptin on LV remodeling consistent with experimental data and may provide insight into the potential role of leptin resistance as a mediator of obesity-associated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Objectives: We tested the association of the adipokines resistin and adiponectin with incident heart failure.Background: Abnormal concentrations of adipokines may partially explain the association between obesity and heart failure.Methods: We related circulating adipokine concentrations to the incidence of heart failure in 2,739 participants in the Framingham Offspring Study.Results: During 6 years of follow-up, 58 participants developed new-onset heart failure. In proportional hazards models (adjusting for age, sex, blood pressure, antihypertensive treatment, diabetes, smoking, total/high-density lipoprotein cholesterol ratio, prevalent coronary heart disease, valvular heart disease, left ventricular hypertrophy, and estimated glomerular filtration rate) using the lowest third of the resistin distribution as the referent, the hazard ratios for heart failure in the middle and top thirds were 2.89 (95% confidence interval [CI]: 1.05 to 7.92) and 4.01 (95% CI: 1.52 to 10.57), respectively (p = 0.004 for trend). Additional adjustment for body mass index, insulin resistance (measured with the homeostasis model), C-reactive protein, and B-type natriuretic peptide did not substantively weaken this association (multivariable hazard ratios [HRs]: 2.62 and 3.74, p = 0.007). In the maximally adjusted model, each SD increment in resistin (7.45 ng/ml) was associated with a 26% increase in heart failure risk (95% CI: 1% to 60%). Concentrations of adiponectin were not associated with heart failure (multivariable HRs: 0.87 and 0.97, p = 0.9).Conclusions: Increased circulating concentrations of resistin were associated with incident heart failure, even after accounting for prevalent coronary heart disease, obesity, and measures of insulin resistance and inflammation. The findings suggest a role for resistin in human disease and a novel pathway to heart failure. [ABSTRACT FROM AUTHOR]

Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC > or =95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD. [ABSTRACT FROM AUTHOR]

Multiple studies have documented an increased incidence of cardiovascular events in the winter, but the pathophysiologic mechanisms remain incompletely understood. It was hypothesized that brachial flow and flow-mediated dilation (FMD) would vary by season and temperature. Season and temperature were related to ultrasonic brachial artery endothelium-dependent FMD% (n = 2,587), baseline flow velocity, and maximal reactive hyperemia (n = 1,973) in the Framingham Offspring Cohort (mean age 61 +/- 10 years, 53% women). Outdoor temperatures were obtained from National Climate Data Center records for Bedford, Massachusetts (about 14 miles from the testing site), and the examination room temperature was measured. In multivariate models, FMD% was highest in summer and lowest in winter (3.01 +/- 0.09% vs 2.56 +/- 0.10%, respectively, p = 0.02 for differences across all 4 seasons). FMD% was highest in the warmest and lowest in the coldest outdoor-temperature quartiles. In stepwise models adjusting for risk factors and selecting among season, outdoor temperature, and room temperature, FMD% was associated with season (p = 0.02); temperature did not enter the model. In contrast, hyperemic flow velocity was significantly lower for cooler and higher for warmer room temperatures (p = 0.02 overall); season did not enter the model. Season and outdoor and room temperature were each retained in a stepwise model of baseline flow velocity (p <0.0001, p = 0.02, and p <0.0001, respectively). In conclusion, a significant association was observed between season and FMD%. Microvascular vasodilator function, as reflected by hyperemic flow velocity, was more strongly related to temperature than season. Endothelial dysfunction may be 1 of the mechanisms influencing seasonal variation in cardiovascular events. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is characterized by structural remodeling and atrial systolic failure. It is unclear if atrial filling abnormalities precede the onset of AF. We evaluated 942 Framingham Study subjects (587 women; mean age 75 years) who underwent Doppler echocardiographic evaluation at a routine examination and who did not have a history of AF. We used multivariable Cox regression models (stratified by gender and prevalent cardiovascular disease) to examine the relations of Doppler transmitral flow indexes (ratio of the velocity-time integrals of the early [E] and late [A] diastolic filling waves [VTI E/A], a correlate of atrial conduit function; E-wave deceleration time; the atrial filling fraction, an index of atrial systolic function; and peak A wave velocity) to the incidence of AF. At follow-up (mean 7 years), 85 subjects (41 women) developed AF. In models adjusting for established risk factors for AF (including left atrial size) at baseline, and for heart failure and myocardial infarction on follow-up, a 1 SD increment in VTI E/A was associated with a 28% increase in risk of AF (hazards ratio 1.28, 95% confidence interval 1.02 to 1.59). A 1 SD decrease in the atrial filling fraction was associated with a 28% higher risk of AF (hazards ratio 1.28, 95% confidence interval 0.98 to 1.67). There was a U-shaped relation between peak A-wave velocity and risk of AF. Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF. [ABSTRACT FROM AUTHOR]