Search

ImportanceAscending thoracic aortic disease is an important cause of sudden death in the US, yet most aortic aneurysms are identified incidentally.ObjectiveTo develop and validate a clinical score to estimate ascending aortic diameter.Design, Setting, and ParticipantsUsing an ongoing magnetic resonance imaging substudy of the UK Biobank cohort study, which had enrolled participants from 2006 through 2010, score derivation was performed in 30 018 participants and internal validation in an additional 6681. External validation was performed in 1367 participants from the Framingham Heart Study (FHS) offspring cohort who had undergone computed tomography from 2002 through 2005, and in 50 768 individuals who had undergone transthoracic echocardiography in the Community Care Cohort Project, a retrospective hospital-based cohort of longitudinal primary care patients in the Mass General Brigham (MGB) network between 2001-2018.ExposuresDemographic and clinical variables (11 covariates that would not independently prompt thoracic imaging).Main Outcomes and MeasuresAscending aortic diameter was modeled with hierarchical group least absolute shrinkage and selection operator (LASSO) regression. Correlation between estimated and measured diameter and performance for identifying diameter 4.0 cm or greater were assessed.ResultsThe 30 018-participant training cohort (52% women), were a median age of 65.1 years (IQR, 58.6-70.6 years). The mean (SD) ascending aortic diameter was 3.04 (0.31) cm for women and 3.32 (0.34) cm for men. A score to estimate ascending aortic diameter explained 28.2% of the variance in aortic diameter in the UK Biobank validation cohort (95% CI, 26.4%-30.0%), 30.8% in the FHS cohort (95% CI, 26.8%-34.9%), and 32.6% in the MGB cohort (95% CI, 31.9%-33.2%). For detecting individuals with an ascending aortic diameter of 4 cm or greater, the score had an area under the receiver operator characteristic curve of 0.770 (95% CI, 0.737-0.803) in the UK Biobank, 0.813 (95% CI, 0.772-0.854) in the FHS, and 0.766 (95% CI, 0.757-0.774) in the MGB cohorts, although the model significantly overestimated or underestimated aortic diameter in external validation. Using a fixed-score threshold of 3.537, 9.7 people in UK Biobank, 1.8 in the FHS, and 4.6 in the MGB cohorts would need imaging to confirm 1 individual with an ascending aortic diameter of 4 cm or greater. The sensitivity at that threshold was 8.9% in the UK Biobank, 11.3% in the FHS, and 18.8% in the MGB cohorts, with specificities of 98.1%, 99.2%, and 96.2%, respectively.Conclusions and RelevanceA prediction model based on common clinically available data was derived and validated to predict ascending aortic diameter. Further research is needed to optimize the prediction model and to determine whether its use is associated with improved outcomes.

Key Points Question Is electronic cigarette (e-cigarette) use associated with incidence of self-reported respiratory disease compared with no use? Findings In this nationally representative cohort of 21 618 US adults from the Population Assessment of Tobacco and Health study, former and current use of e-cigarettes were associated with increased risk of developing a respiratory condition compared with no prior use of e-cigarettes, independent of other tobacco product use. Meaning These findings suggest that users of e-cigarettes may experience increased rates of respiratory conditions independent of other tobacco product use., This cohort study examines the association of electronic cigarette use with incidence of respiratory conditions among participants of the Population Assessment of Tobacco and Health Study., Importance Generating robust and timely evidence about the respiratory health risks of electronic cigarettes (e-cigarettes) is critical for informing state and federal regulatory standards for product safety. Objective To examine the association of e-cigarette use with incident respiratory conditions, including chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma. Design, Setting, and Participants This prospective cohort study used data from the nationally representative cohort of US adults from the Population Assessment of Tobacco and Health (PATH) study, including wave 1 from 2013 to 2014, wave 2 from 2014 to 2015, wave 3 from 2015 to 2016, and wave 4 from 2016 to 2018. Individuals aged 18 years and older at baseline with no prevalent respiratory conditions were included in the analyses. Analyses were conducted from February to July 2020. Exposures e-Cigarette use was assessed by self-reported current use status (never, former, or current) at baseline. Main Outcomes and Measures Incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma, as well as a composite respiratory disease encompassing all 4 conditions. Results Among 21 618 respondents included in the analyses, 11 017 (491%) were men and 12 969 (65.2%) were non-Hispanic White. A total of 14 213 respondents were never e-cigarette users, 5076 respondents (11.6%) were former e-cigarette users, and 2329 respondents (5.2%) were current e-cigarette users. Adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, there was an increased risk of respiratory disease among former e-cigarette uses (incidence rate ratio [IRR], 1.28; 95% CI, 1.09-1.50) and current e-cigarette users (IRR, 1.31; 95% CI, 1.08-1.59). Among respondents with good self-rated health, the IRR for former e-cigarette users was 1.21 (95%CI, 1.00-1.46) and the IRR for current e-cigarette users was 1.43 (95% CI, 1.14-1.79). For specific respiratory diseases among current e-cigarette users, the IRR was 1.33 (95% CI, 1.06-1.67) for chronic bronchitis, 1.69 (95% CI, 1.15-2.49) for emphysema, 1.57 (95% CI, 1.15-2.13) for COPD, and 1.31 (95% CI, 1.01-1.71) for asthma. Conclusions and Relevance This cohort study found that e-cigarette use was associated with an increased risk of developing respiratory disease independent of cigarette smoking. These findings add important evidence on the risk profile of novel tobacco products.

Key Points Question Is electronic cigarette (e-cigarette) use among tobacco-naive youths associated with subsequent risk of cigarette initiation? Findings In this cohort study using data from the Population Assessment of Tobacco and Health Study (2013-2016), youths whose first tobacco product was an e-cigarette were more likely to initiate cigarettes over 2 years of follow-up. At the population level, approximately 180 000 new ever smokers and 45 000 current smokers in the United States over 2 years may have started smoking combustible cigarettes after initiating e-cigarette use. Meaning Tobacco-naive youths who initiate e-cigarettes may be at greater risk of subsequently initiating cigarette smoking., Importance The use of electronic cigarettes (e-cigarettes) and other noncigarette tobacco products may increase the odds of cigarette initiation, even among low-risk youths. Objective To evaluate the associations of prior e-cigarette use and other tobacco product use with subsequent cigarette initiation within 2 years of follow-up. Design, Setting, and Participants In this prospective cohort study, data from waves 1 through 3 of the Population Assessment of Tobacco and Health Study (2013-2016) were used to assess youths aged 12 to 15 years who had never used cigarettes, e-cigarettes, or other tobacco products at wave 1. This was a nationally representative study of the US population. Data analysis was conducted in 2018. Exposures First noncigarette tobacco product used (none, e-cigarette, or other tobacco product) between wave 1 and wave 3. Main Outcomes and Measures Ever cigarette use and current cigarette use at wave 3. Results In the sample (N = 6123), respondents were 49.5% female; 54.1% non-Hispanic, white; and the mean (SD) age was 13.4 (1.2) years. Of these, 8.6% reported e-cigarettes as their first tobacco product, while 5.0% reported using another noncigarette product first; 3.3% reported using cigarettes first. Cigarette use at wave 3 was higher among prior e-cigarette users (20.5%) compared with youths with no prior tobacco use (3.8%). Prior e-cigarette use was associated with more than 4 times the odds of ever cigarette use (odds ratio, 4.09; 95% CI, 2.97-5.63) and nearly 3 times the odds of current cigarette use (odds ratio, 2.75; 95% CI, 1.60-4.73) compared with no prior tobacco use. Prior use of other tobacco products was similarly associated with subsequent ever cigarette use (OR, 3.84; 95% CI, 2.63-5.63) and current cigarette use (OR, 3.43; 95% CI, 1.88-6.26) compared with no prior tobacco use. The association of prior e-cigarette use with cigarette initiation was stronger among low-risk youths (OR, 8.57; 95% CI, 3.87-18.97), a pattern not seen for prior other product use. Over the 2 years between 2013 and 2014 and 2015 and 2016, 21.8% of new cigarette ever use (178 850 youths) and 15.3% of current cigarette use (43 446 youths) among US youths aged 12 to 15 years may be attributable to prior e-cigarette use. Conclusions and Relevance This study’s findings support the notion that e-cigarette use is associated with increased risk for cigarette initiation and use, particularly among low-risk youths. At the population level, the use of e-cigarettes may be a contributor to the initiation of cigarette smoking among youths., This cohort study evaluates whether prior use of electronic cigarettes (e-cigarettes) and other tobacco products by US youths is associated with subsequent initation of cigarette smoking.

Importance Atrial fibrillation (AF) is the most common arrhythmia affecting 1% of the population. Young individuals with AF have a strong genetic association with the disease, but the mechanisms remain incompletely understood. Objective To perform large-scale whole-genome sequencing to identify genetic variants related to AF. Design, setting, and participants The National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Program includes longitudinal and cohort studies that underwent high-depth whole-genome sequencing between 2014 and 2017 in 18 526 individuals from the United States, Mexico, Puerto Rico, Costa Rica, Barbados, and Samoa. This case-control study included 2781 patients with early-onset AF from 9 studies and identified 4959 controls of European ancestry from the remaining participants. Results were replicated in the UK Biobank (346 546 participants) and the MyCode Study (42 782 participants). Exposures Loss-of-function (LOF) variants in genes at AF loci and common genetic variation across the whole genome. Main outcomes and measures Early-onset AF (defined as AF onset in persons Results Among 2781 participants with early-onset AF (the case group), 72.1% were men, and the mean (SD) age of AF onset was 48.7 (10.2) years. Participants underwent whole-genome sequencing at a mean depth of 37.8 fold and mean genome coverage of 99.1%. At least 1 LOF variant in TTN, the gene encoding the sarcomeric protein titin, was present in 2.1% of case participants compared with 1.1% in control participants (odds ratio [OR], 1.76 [95% CI, 1.04-2.97]). The proportion of individuals with early-onset AF who carried a LOF variant in TTN increased with an earlier age of AF onset (P value for trend, 4.92 × 10-4), and 6.5% of individuals with AF onset prior to age 30 carried a TTN LOF variant (OR, 5.94 [95% CI, 2.64-13.35]; P = 1.65 × 10-5). The association between TTN LOF variants and AF was replicated in an independent study of 1582 patients with early-onset AF (cases) and 41 200 control participants (OR, 2.16 [95% CI, 1.19-3.92]; P = .01). Conclusions and relevance In a case-control study, there was a statistically significant association between an LOF variant in the TTN gene and early-onset AF, with the variant present in a small percentage of participants with early-onset AF (the case group). Further research is necessary to understand whether this is a causal relationship.

Importance Atrial fibrillation (AF) contributes to substantial morbidity, mortality, and health care expenditures. Accurate prediction of incident AF would enhance AF management and potentially improve patient outcomes. Objective To validate the AF risk prediction model originally developed by the Cohorts for Heart and Aging Research in Genomic Epidemiology–Atrial Fibrillation (CHARGE-AF) investigators using a large repository of electronic medical records (EMRs). Design, Setting, and Participants In this prediction model study, deidentified EMRs of 33 494 individuals 40 years or older who were white or African American and had no history of AF were reviewed and analyzed. The participants were followed up in the internal medicine outpatient clinics at Vanderbilt University Medical Center for incident AF from December 31, 2005, until December 31, 2010. Adjusting for differences in baseline hazard, the CHARGE-AF Cox proportional hazards model regression coefficients were applied to the EMR cohort. A simple version of the model with no echocardiographic variables was also evaluated. Data were analyzed from October 31, 2013, to January 31, 2014. Main Outcomes and Measures Incident AF. Predictors in the model included age, race, height, weight, systolic and diastolic blood pressure, treatment for hypertension, smoking status, type 2 diabetes, heart failure, history of myocardial infarction, left ventricular hypertrophy, and PR interval. Results Among the 33 494 participants, the median age was 57 (interquartile range, 49-67) years; 57% of patients were women, 43% were men, 85.7% were white, and 14.3% were African American. During the mean (SD) follow-up of 4.8 (0.9) years, 2455 individuals (7.3%) developed AF. Both models had poor calibration in the EMR cohort, with underprediction of AF among low-risk individuals and overprediction of AF among high-risk individuals (10th and 90th percentiles for predicted probability of incident AF, 0.005 and 0.179, respectively). The full CHARGE-AF model had a C index of 0.708 (95% CI, 0.699-0.718) in our cohort. The simple model had similar discrimination (C index, 0.709; 95% CI, 0.699-0.718; P = .70 for difference between models). Conclusions and Relevance Despite reasonable discrimination, the CHARGE-AF models showed poor calibration in this EMR cohort. This study highlights the difficulties of applying a risk model derived from prospective cohort studies to an EMR cohort and suggests that these AF risk prediction models be used with caution in the EMR setting. Future risk models may need to be developed and validated within EMR cohorts.

New-onset atrial fibrillation (AF) has been reported in 6% to 20% of patients with severe sepsis. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain.To determine the in-hospital stroke and in-hospital mortality risks associated with new-onset AF in patients with severe sepsis.Retrospective population-based cohort of California State Inpatient Database administrative claims data from nonfederal acute care hospitals for January 1 through December 31, 2007.Data were available for 3,144,787 hospitalized adults. Severe sepsis (n = 49,082 [1.56%]) was defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission.A priori outcome measures were in-hospital ischemic stroke (ICD-9-CM codes 433, 434, or 436) and mortality.Patients with severe sepsis were a mean age of 69 (SD, 16) years and 48% were women. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis (multivariable-adjusted odds ratio [OR], 6.82; 95% CI, 6.54-7.11; P.001). Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 [2.6%] vs 306/46,186 [0.6%] strokes; adjusted OR, 2.70; 95% CI, 2.05-3.57; P.001) and in-hospital mortality (1629 [56%] vs 18,027 [39%] deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P.001). Findings were robust across 2 definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses.Among patients with severe sepsis, patients with new-onset AF were at increased risk of in-hospital stroke and death compared with patients with no AF and patients with preexisting AF.

Vascular stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Vascular stiffness and blood pressure pulsatility are related; however, temporal relationships between vascular stiffening and blood pressure elevation have not been fully delineated.To examine temporal relationships among vascular stiffness, central hemodynamics, microvascular function, and blood pressure progression.Longitudinal community-based cohort study conducted in Framingham, Massachusetts. The present investigation is based on the 2 latest examination cycles (cycle 7: 1998-2001; cycle 8: 2005-2008 [last visit: January 25, 2008]) of the Framingham Offspring study (recruited: 1971-1975). Temporal relationships among blood pressure and 3 measures of vascular stiffness and pressure pulsatility derived from arterial tonometry (carotid-femoral pulse wave velocity [CFPWV], forward wave amplitude [FWA], and augmentation index) were examined over a 7-year period in 1759 participants (mean [SD] age: 60 [9] years; 974 women).The primary outcomes were blood pressure and incident hypertension during examination cycle 8. The secondary outcomes were CFPWV, FWA, and augmentation index during examination cycle 8.In a multivariable-adjusted regression model, higher FWA (β, 1.3 [95% CI, 0.5-2.1] mm Hg per 1 SD; P = .002) and higher CFPWV (β, 1.5 [95% CI, 0.5-2.6] mm Hg per 1 SD; P = .006) during examination cycle 7 were jointly associated with systolic blood pressure during examination cycle 8. Similarly, in a model that included systolic and diastolic blood pressure and additional risk factors during examination cycle 7, higher FWA (odds ratio [OR], 1.6 [95% CI, 1.3-2.0] per 1 SD; P.001), augmentation index (OR, 1.7 [95% CI, 1.4-2.0] per 1 SD; P.001), and CFPWV (OR, 1.3 [95% CI, 1.0-1.6] per 1 SD; P = .04) were associated with incident hypertension during examination cycle 8 (338 cases [32%] in 1048 participants without hypertension during examination cycle 7). Conversely, blood pressure during examination cycle 7 was not associated with CFPWV during examination cycle 8. Higher resting brachial artery flow (OR, 1.23 [95% CI, 1.04-1.46]) and lower flow-mediated dilation (OR, 0.80 [95% CI, 0.67-0.96]) during examination cycle 7 were associated with incident hypertension (in models that included blood pressure and tonometry measures collected during examination cycle 7).In this cohort, higher aortic stiffness, FWA, and augmentation index were associated with higher risk of incident hypertension; however, initial blood pressure was not independently associated with risk of progressive aortic stiffening.

CONTEXT: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown.OBJECTIVE: To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors.DESIGN, SETTING, AND PARTICIPANTS: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007.MAIN OUTCOME MEASURES: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ≤65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF.RESULTS: Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of 10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009).CONCLUSIONS: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

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 Determination of C-reactive protein (CRP) level has been suggested to improve cardiovascular disease (CVD) risk assessment. This study examines the utility of CRP levels to assess CVD risk in a community setting. Methods We performed a prospective observational cohort study on a community population sample. A total of 1949 men and 2497 women without CVD from the Framingham Heart Study underwent CVD risk factor assessment. Initial CVD events during 8 years of follow-up were recorded. Results There were 283 major CVD and 160 major coronary heart disease incident events. Age-, sex-, and multivariable-adjusted analyses generally used CRP level categories of less than 1, 1 to 3, and greater than 3 mg/L. In age- and sex-adjusted models, the traditional risk factors and elevated CRP levels indicated increased risk. The age- and sex-adjusted relative risk (RR) and 95% confidence interval (CI) of CRP level greater than 3 mg/L for major CVD was elevated (RR, 1.60; 95% CI, 1.19-2.14), with evidence of attenuation (RR, 1.22; 95% CI, 0.90-1.66) in multivariable models. The C statistic, a measure of the discriminatory capability of the prediction models, was 0.74 for prediction of major CVD with age and CRP level. In multivariable models that included traditional risk factors, the C statistic was 0.78, a value that was unchanged with the addition of CRP to the multivariable model. Similar relations were noted for major coronary heart disease events. Conclusion Elevated CRP level provided no further prognostic information beyond traditional office risk factor assessment to predict future major CVD and major coronary heart disease in this population sample.

ContextObesity is associated with atrial enlargement and ventricular diastolic dysfunction, both known predictors of atrial fibrillation (AF). However, it is unclear whether obesity is a risk factor for AF.ObjectiveTo examine the association between body mass index (BMI) and the risk of developing AF.Design, Setting, and ParticipantsProspective, community-based observational cohort in Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898 women [55%]) without baseline AF (electrocardiographic AF or arterial flutter). Body mass index (calculated as weight in kilograms divided by square of height in meters) was evaluated as both a continuous and a categorical variable (normal defined as

ContextPrior risk stratification schemes for atrial fibrillation (AF) have been based on randomized trial cohorts or Medicare administrative databases, have included patients with established AF, and have focused on stroke as the principal outcome.ObjectiveTo derive risk scores for stroke alone and stroke or death in community-based individuals with new-onset AF.Design, Setting, and ParticipantsProspective, community-based, observational cohort in Framingham, Mass. We identified 868 participants with new-onset AF, 705 of whom were not treated with warfarin at baseline. Risk scores for stroke (ischemic or hemorrhagic) and stroke or death were developed with censoring when warfarin initiation occurred during follow-up. Event rates were examined in low-risk individuals, as defined by the risk score and 4 previously published risk schemes.Main Outcome MeasuresStroke and the combination of stroke or death.ResultsDuring a mean follow-up of 4.0 years free of warfarin use, stroke alone occurred in 83 participants and stroke or death occurred in 382 participants. A risk score for stroke was derived that included the following risk predictors: advancing age, female sex, increasing systolic blood pressure, prior stroke or transient ischemic attack, and diabetes. With the risk score, 14.3% of the cohort had a predicted 5-year stroke rate ≤7.5% (average annual rate ≤1.5%), and 30.6% of the cohort had a predicted 5-year stroke rate ≤10% (average annual rate ≤2%). Actual stroke rates in these low-risk groups were 1.1 and 1.5 per 100 person-years, respectively. Previous risk schemes classified 6.4% to 17.3% of subjects as low risk, with actual stroke rates of 0.9 to 2.3 per 100 person-years. A risk score for stroke or death is also presented.ConclusionThese risk scores can be used to estimate the absolute risk of an adverse event in individuals with AF, which may be helpful in counseling patients and making treatment decisions.

ContextSeveral reports have suggested the usefulness of plasma brain natriuretic peptide (BNP) as a screening test for left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD). Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women.ObjectivesTo examine the usefulness of natriuretic peptides for screening for elevated LV mass and LVSD in the community.Design, Setting, and ParticipantsCommunity-based prospective cohort study of 3177 participants (1707 women) from the Framingham Study who attended a routine examination in 1995-1998.Main Outcome MeasuresReceiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values, and likelihood ratios for identifying elevated LV mass (sex-specific 90th percentile or higher of LV mass/[height]2), LVSD (ejection fraction ≤50% and/or fractional shortening

The syndrome of congestive heart failure with preserved left ventricular systolic function is common in clinical practice. The signs and symptoms of the disorder are similar to those of congestive heart failure with left ventricular systolic dysfunction, underscoring a need for routine evaluation of left and right ventricular systolic function in patients with congestive heart failure. The syndrome may be related to anatomic abnormalities that increase the resistance to ventricular filling, or to physiologic abnormalities of myocardial relaxation or compliance. Advancing age, often in association with hypertension, coronary artery disease, tachycardia, and atrial fibrillation, is commonly associated with the disorder. Randomized controlled clinical trials are needed to evaluate the efficacy of various therapeutic agents in reducing the risks associated with diastolic heart failure.

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. ( JAMA . 1994;272:33-36)

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 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. (JAMA. 1994;271:840-844)