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Thomas J Wang

Publications and source records attributed to Thomas J Wang.

At least 19 recordsLinked to original sources
PubMed2006

Multiple biomarkers for the prediction of first major cardiovascular events and death.

BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.

Biomarkers↗
PubMed2006

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.

Adult↗
PubMed2006

Endogenous sex hormones and cardiovascular disease incidence in men.

BACKGROUND: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. OBJECTIVE: To examine the association of circulating sex hormone levels and CVD risk in men. DESIGN: Prospective cohort study. SETTING: Community-based study in Framingham, Massachusetts. PARTICIPANTS: 2084 middle-aged white men without CVD at baseline. MEASUREMENTS: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. RESULTS: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% CI, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age >56 years) men (hazard ratio per SD increment, 0.86 [CI, 0.78 to 0.96]; P = 0.005) but not in younger (median age < or =56 years) men (hazard ratio per SD increment, 1.11 [CI, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. LIMITATIONS: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. CONCLUSIONS: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men.

Cardiovascular Diseases↗
PubMed2006

Association of parental heart failure with risk of heart failure in offspring.

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.

Adult Children↗
PubMed2006

Electrocardiographic QRS duration and the risk of congestive heart failure: the Framingham Heart Study.

Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants (mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, <100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, > or =120 ms]. During follow-up (mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P<0.001]. In time- dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P=0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P<0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk.

Aged↗
PubMed2006

Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function.

BACKGROUND: Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function. METHODS AND RESULTS: We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P=0.001 and P=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P=0.01). None of the other biomarkers was significantly related to the vascular function measures studied. CONCLUSIONS: In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.

Aged↗
PubMed2006

Screening for ventricular remodeling.

Current guidelines emphasize the importance of preventing heart failure (HF) by targeting people with preclinical forms of the disease. Accordingly, there is considerable interest in identifying left ventricular (LV) remodeling, the fundamental substrate for HF, in asymptomatic individuals in the community. Increased LV mass and asymptomatic LV systolic and LV diastolic dysfunction are the remodeling phenotypes that could be potentially considered for population-wide screening. Plasma levels of natriuretic peptides (NP) have been extensively investigated for such screening purposes. However, a majority of investigations suggest that their performance characteristics are suboptimal for identifying LV remodeling phenotypes unless high-risk individuals (eg, older men with hypertension) are targeted. In general, the prevalence of LV systolic dysfunction in women is too low to justify screening. In recent reports, sequential screening strategies combining urine and plasma NP or plasma NP and hand-held portable echocardiography have been advocated as potential approaches to identify asymptomatic LV systolic dysfunction in a cost-effective manner. Additional studies are warranted to confirm these findings.

Biomarkers↗
PubMed2006

Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample.

STUDY OBJECTIVES: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample. DESIGN: Cross-sectional, retrospective, observational study. SETTING: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study. PARTICIPANTS: Community-based sample of 623 individuals. MEASUREMENTS: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates. RESULTS: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed forAHI categories 5-15, 15-30, >30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0.93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index. CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels.

Atrial Fibrillation↗
PubMed2005

Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults.

CONTEXT: While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear. OBJECTIVE: To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors. DESIGN, SETTING, AND PARTICIPANTS: The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least 1 sibling in the study; all were followed up for 8 years. MAIN OUTCOME MEASURES: Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence. RESULTS: Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% CI, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% CI, 1.32-3.00) exceeded that for parental CVD (1.45; 95% CI, 1.02-2.05). CONCLUSION: Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults.

Cardiovascular Diseases↗
PubMed2005

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.

Albuminuria↗
PubMed2005

Cross-sectional relations of electrocardiographic QRS duration to left ventricular dimensions: the Framingham Heart Study.

OBJECTIVES: The goal of this study was to assess the relations of electrocardiographic QRS duration to left ventricular (LV) measurements in individuals without heart failure (HF) or prior myocardial infarction (MI). BACKGROUND: Increased electrocardiographic QRS duration (>/=120 ms) is a marker of ventricular dyssynchrony. METHODS: We evaluated the relations of maximal electrocardiographic QRS duration to echocardiographic LV dimensions in 4,534 Framingham Heart study participants (mean age 54 years, 57% women) without prior HF or MI. QRS duration was analyzed as a continuous variable and as categories (<100, 100 to 119, and >/=120 ms). RESULTS: In linear regression models, LV mass, end-diastolic dimension, and septal and posterior wall thicknesses were positively related to log-QRS duration, whereas fractional shortening (FS) was inversely related (p < 0.001). There was a significant trend for increasing LV mass and dimensions, and decreasing FS across categories of QRS duration (p < 0.001). Left bundle branch block was associated with higher LV mass and lower FS compared with a normal QRS duration (p < 0.001). CONCLUSIONS: In our community-based sample of individuals free of HF and MI, increasing electrocardiographic QRS duration was positively related to LV mass and dimensions, and inversely associated with LV FS. Additional investigations are warranted to elucidate the mechanisms underlying the observed associations.

Adult↗
PubMed2005

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.

Albuminuria↗
PubMed2004

Obesity and the risk of new-onset atrial fibrillation.

CONTEXT: Obesity 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. OBJECTIVE: To examine the association between body mass index (BMI) and the risk of developing AF. DESIGN, SETTING, AND PARTICIPANTS: Prospective, 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 <25.0; overweight, 25.0 to <30.0; and obese, > or =30.0). In addition to adjusting for clinical confounders by multivariable techniques, we also examined models including echocardiographic left atrial diameter to examine whether the influence of obesity was mediated by changes in left atrial dimensions. MAIN OUTCOME MEASURE: Association between BMI or BMI category and risk of developing new-onset AF. RESULTS: During a mean follow-up of 13.7 years, 526 participants (234 women) developed AF. Age-adjusted incidence rates for AF increased across the 3 BMI categories in men (9.7, 10.7, and 14.3 per 1000 person-years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable models adjusted for cardiovascular risk factors and interim myocardial infarction or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was observed in men (95% confidence interval [CI], 1%-7%; P = .02) and in women (95% CI, 1%-7%; P = .009). Adjusted hazard ratios for AF associated with obesity were 1.52 (95% CI, 1.09-2.13; P = .02) and 1.46 (95% CI, 1.03-2.07; P = .03) for men and women, respectively, compared with individuals with normal BMI. After adjustment for echocardiographic left atrial diameter in addition to clinical risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios per 1-unit increase in BMI, 1.00 [95% CI, 0.97-1.04], P = .84 in men; 0.99 [95% CI, 0.96-1.02], P = .56 in women). CONCLUSIONS: Obesity is an important, potentially modifiable risk factor for AF. The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF.

Adult↗
PubMed2004

Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. METHODS AND RESULTS: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. CONCLUSIONS: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

Adult↗
PubMed2004

Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring.

CONTEXT: Atrial fibrillation (AF) is the most common cardiac dysrhythmia in the United States. Whereas rare cases of familial AF have been reported, it is unknown if AF among unselected individuals is a heritable condition. OBJECTIVE: To determine whether parental AF increases the risk for the development of offspring AF. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1983-2002) within the Framingham Heart Study, a population-based epidemiologic study. Participants were 2243 offspring (1165 women, 1078 men) at least 30 years of age and free of AF whose parents had both been evaluated in the original cohort. MAIN OUTCOME MEASURES: Development of new-onset AF in the offspring was prospectively examined in association with previously documented parental AF. RESULTS: Among 2243 offspring participants, 681 (30%) had at least 1 parent with documented AF; 70 offspring participants (23 women; mean age, 62 [range, 40-81] years) developed AF in follow-up. Compared with no parental AF, AF in at least 1 parent increased the risk of offspring AF (multivariable-adjusted odds ratio [OR], 1.85; 95% confidence interval [CI], 1.12-3.06; P =.02). These results were stronger when age was limited to younger than 75 years in both parents and offspring (multivariable-adjusted OR, 3.23; 95% CI, 1.87-5.58; P<.001) and when the sample was further limited to those without antecedent myocardial infarction, heart failure, or valve disease (multivariable-adjusted OR, 3.17; 95% CI, 1.71-5.86; P<.001). CONCLUSIONS: Parental AF increases the future risk for offspring AF, an observation supporting a genetic susceptibility to developing this dysrhythmia. Further research into the genetic factors predisposing to AF is warranted.

Adult↗
PubMed2004

Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.

CONTEXT: Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. OBJECTIVE: To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. DESIGN: Inception cohort study. SETTING: Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. PARTICIPANTS: All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. MAIN OUTCOME MEASURES: We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. RESULTS: Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. CONCLUSIONS: Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.

Adult Children↗
PubMed2004

Plasma natriuretic peptide levels and the risk of cardiovascular events and death.

BACKGROUND: The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and cardiovascular remodeling. The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established. METHODS: We prospectively studied 3346 persons without heart failure. Using proportional-hazards regression, we examined the relations of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide to the risk of death from any cause, a first major cardiovascular event, heart failure, atrial fibrillation, stroke or transient ischemic attack, and coronary heart disease. RESULTS: During a mean follow-up of 5.2 years, 119 participants died and 79 had a first cardiovascular event. After adjustment for cardiovascular risk factors, each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death (P=0.009), a 28 percent increase in the risk of a first cardiovascular event (P=0.03), a 77 percent increase in the risk of heart failure (P<0.001), a 66 percent increase in the risk of atrial fibrillation (P<0.001), and a 53 percent increase in the risk of stroke or transient ischemic attack (P=0.002). Peptide levels were not significantly associated with the risk of coronary heart disease events. B-type natriuretic peptide values above the 80th percentile (20.0 pg per milliliter for men and 23.3 pg per milliliter for women) were associated with multivariable-adjusted hazard ratios of 1.62 for death (P=0.02), 1.76 for a first major cardiovascular event (P=0.03), 1.91 for atrial fibrillation (P=0.02), 1.99 for stroke or transient ischemic attack (P=0.02), and 3.07 for heart failure (P=0.002). Similar results were obtained for N-terminal pro-atrial natriuretic peptide. CONCLUSIONS: In this community-based sample, plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors. Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure.

Atrial Natriuretic Factor↗