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Congenital heart disease (CHD) comprises a range of structural anomalies, each with a unique natural history, evolving treatment strategies, and distinct long-term consequences. Current prediction models are challenged by generalizability, limited validation, and questionable application to extended follow-up periods. In this JACC Scientific Statement, we tackle the difficulty of risk measurement across the lifespan. We appraise current and future risk measurement frameworks and describe domains of risk specific to CHD. Risk of adverse outcomes varies with age, sex, genetics, era, socioeconomic status, behavior, and comorbidities as they evolve through the lifespan and across care settings. Emerging technologies and approaches promise to improve risk assessment, but there is also need for large, longitudinal, representative, prospective CHD cohorts with multidimensional data and consensus-driven methodologies to provide insight into time-varying risk. Communication of risk, particularly with patients and their families, poses a separate and equally important challenge, and best practices are reviewed., Competing Interests: Funding Support and Author Disclosures Dr Opotowsky is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL151604. Dr Marelli is supported by a Canadian Institutes of Health Research Foundation grant (no. 148462). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor., Objectives: This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use., Methods: Stable thromboxane B 2 metabolites (TXB 2 -M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB 2 -M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling., Results: In 1,363 (44.8%) participants taking ASA at the index examination, median TXB 2 -M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB 2 -M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB 2 -M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB 2 -M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB 2 -M., Conclusions: Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD., Competing Interests: Funding Support and Author Disclosures This study was supported by a grant from American Heart Association (17GRNT3360007 to Dr Rade). The parent Framingham Heart Study was supported by contracts NO1-HC-25195, HHSN268201500001I, and 75N92019D00031 from the National Heart, Lung, and Blood Institute. Dr Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. The authors had sole control of the design of the study, collection, analyses, and dissemination of the data. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The residual lifetime risk (RLR) of developing heart failure (HF) may have changed over time because of the increasing population burden of hypertension, obesity, and diabetes; greater survival after myocardial infarction; and a greater lifespan., Objectives: The authors assessed changes in the RLR for HF in two 25-year epochs (1965-1989 and 1990-2014)., Methods: We compared the RLR of HF at age 50 years (adjusting for competing risk of death) in the 2 epochs in Framingham Study participants overall and in the following strata: sex, body mass index, blood pressure, and diabetes., Results: Mean life expectancy increased from 75.9 to 82.1 years in women and 72.5 to 78.1 years in men. We observed 624 HF events over 111,351 person-observations in epoch 1, and 875 HF events over 128,903 person-observations in epoch 2. The mean age at onset of HF increased across the epochs by 6.6 years (women) to 7.2 years (men). The RLR of HF at age 50 years increased across epochs from 18.86% to 22.55% (absolute increase 3.69; 95% CI: 0.90-6.49; P = 0.01) in women, and from 19.19% to 25.25% (absolute increase 6.06; 95% CI: 3.08-9.04; P < 0.001) in men. The increase in RLR of HF in the second epoch was consistent across strata with excess body mass index or higher blood pressure (relative increase of 28%-47%) and in participants without prior myocardial infarction (relative increase of 23%)., Conclusions: The RLR of HF has increased in our community-based sample of White individuals over the last 5 decades, possibly caused by an increase in life expectancy., Competing Interests: Funding Support and Author Disclosures This work is supported by Contracts NO1-HC-25195, HHSN268201500001I, and 75N92019D00031 from the National Heart, Lung, and Blood Institute. Dr Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The Framingham Heart Study is the longest-running cardiovascular epidemiological study, starting in 1948. This paper gives an overview of the various cohorts, collected data, and most important research findings to date. In brief, the Framingham Heart Study, funded by the National Institutes of Health and managed by Boston University, spans 3 generations of well phenotyped White persons and 2 cohorts comprised of racial and ethnic minority groups. These cohorts are densely phenotyped, with extensive longitudinal follow-up, and they continue to provide us with important information on human cardiovascular and noncardiovascular physiology over the lifespan, as well as to identify major risk factors for cardiovascular disease. This paper also summarizes some of the more recent progress in molecular epidemiology and discusses the future of the study., Competing Interests: Funding Support and Author Disclosures Dr. Nayor is supported by the National Heart, Lung, and Blood Institute (K23-HL138260). Dr. Tsao is supported by the National Institutes of Health (5R03-HL145195). Dr. Levy is supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Background: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear., Objectives: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF., Methods: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio., Results: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001)., Conclusions: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Blood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified., Objective: The authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures., Methods: The authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke., Results: A total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk., Conclusions: Cumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Extended elevations of non-high-density lipoprotein cholesterol (non-HDL-C) across a lifespan are associated with increased risk of cardiovascular disease (CVD). However, optimal testing intervals to identify individuals with high lipid-related CVD risk are unknown., Objectives: This study determined the extent to which lipid levels in young adulthood predict future lipid trajectories and associated long-term CVD risk., Methods: A sample of 2,516 Framingham Offspring study participants 25 to 40 years of age free of CVD and diabetes had their non-HDL-C progression modeled over 8 study examinations (mean follow-up 32.6 years) using group-based methods. CVD risk based on 25 to 30 years of follow-up was evaluated using Kaplan-Meier analyses for those with mean non-HDL-C ≥160 mg/dl ("high") and <130 mg/dl ("low") at the first 2 examinations. Levels of non-HDL-C for participants on lipid treatment were adjusted by nonparametric algorithm., Results: The trajectories of the lipid levels were generally stable over the 30-year life course; mean non-HDL-C measured in young adulthood were highly predictive of levels later in life. Individuals could be reliably assigned to high and low non-HDL-C groups based on 2 measurements collected between 25 to 40 years of age. Overall, 80% of those with non-HDL-C ≥160 mg/dl at the first 2 exams remained in the high group on subsequent 25-year testing, whereas 88% of those with non-HDL-C <130 mg/dl remained below 160 mg/dl. Those with high non-HDL-C in young adulthood had a 22.6% risk of CVD in the next 25 years as compared with a 6.4% risk in those with low non-HDL-C., Conclusions: Most adults with elevated non-HDL-C early in life continue to have high non-HDL-C over their life course, leading to significantly increased risk of CVD. The results demonstrate that early lipid monitoring before 40 years of age would identify a majority of those with a high likelihood for lifetime elevated lipid levels who also have a high long-term risk for CVD. This information could facilitate informed patient-provider discussion about the potential benefits of preventive lipid-lowering efforts during the early midlife period., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors., Background: Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups., Methods: We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects., Results: Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p < 0.001) for coronary heart disease, 1.54 (95% CI: 1.34 to 1.78; p < 0.001) for stroke, and 1.45 (95% CI: 1.30 to 1.61; p < 0.001) for CVD. Associations stratified according to sex, diabetes, and hypertension were similar but decreased with age (1.89, 1.77, 1.36, and 1.23 for age ≤50, 51 to 60, 61 to 70, and >70 years, respectively; pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor of coronary heart disease (HR: 1.23 [95% CI: 1.11 to 1.35]; p < 0.001), stroke (HR: 1.28 [95% CI: 1.16 to 1.42]; p < 0.001), and CVD events (HR: 1.30 [95% CI: 1.18 to 1.43]; p < 0.001). Reclassification indices showed that the addition of aPWV improved risk prediction (13% for 10-year CVD risk for intermediate risk) for some subgroups., Conclusions: Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to examine the relation of galectin-3 (Gal-3), a marker of cardiac fibrosis, with incident heart failure (HF) in the community., Background: Gal-3 is an emerging prognostic biomarker in HF, and experimental studies suggest that Gal-3 is an important mediator of cardiac fibrosis. Whether elevated Gal-3 concentrations precede the development of HF is unknown., Methods: Gal-3 concentrations were measured in 3,353 participants in the Framingham Offspring Cohort (mean age 59 years; 53% women). The relation of Gal-3 to incident HF was assessed using proportional hazards regression., Results: Gal-3 was associated with increased left ventricular mass in age-adjusted and sex-adjusted analyses (p = 0.001); this association was attenuated in multivariate analyses (p = 0.06). A total of 166 participants developed incident HF and 468 died during a mean follow-up period of 11.2 years. Gal-3 was associated with risk for incident HF (hazard ratio [HR]: 1.28 per 1 SD increase in log Gal-3; 95% confidence interval [CI]: 1.14 to 1.43; p < 0.0001) and remained significant after adjustment for clinical variables and B-type natriuretic peptide (HR: 1.23; 95% CI: 1.04 to 1.47; p = 0.02). Gal-3 was also associated with risk for all-cause mortality (multivariable-adjusted HR: 1.15; 95% CI: 1.04 to 1.28; p = 0.01). The addition of Gal-3 to clinical factors resulted in negligible changes to the C-statistic and minor improvements in net reclassification improvement., Conclusions: Higher concentration of Gal-3, a marker of cardiac fibrosis, is associated with increased risk for incident HF and mortality. Future studies evaluating the role of Gal-3 in cardiac remodeling may provide further insights into the role of Gal-3 in the pathophysiology of HF., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the relationship between sex hormones and natriuretic peptide levels in community-based adults., Background: Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear. Experimental studies suggest that androgens may suppress natriuretic peptide secretion., Methods: We measured N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone-binding globulin plasma levels in 4,056 men and women (mean age 40 ± 9 years) from the Framingham Heart Study Third-Generation cohort. Sex/hormone status was grouped as: 1) men; 2) post-menopausal women not receiving hormone replacement therapy; 3) pre-menopausal women not receiving hormonal contraceptives; 4) post-menopausal women receiving hormone replacement therapy; and 5) pre-menopausal women receiving hormonal contraceptives., Results: Circulating NT-proBNP levels were associated with sex/hormone status (overall p < 0.0001). Men had lower NT-proBNP levels than women of all menopause or hormone groups, and women receiving hormonal contraceptives had higher NT-proBNP levels than women who were not receiving hormone therapy (all p < 0.0001). These relationships remained significant after adjusting for age, body mass index, and cardiovascular risk factors. Across sex/hormone status groups, free testosterone (FT) levels decreased and sex hormone-binding globulin levels increased in tandem with increasing NT-proBNP levels. In sex-specific analyses, NT-proBNP levels decreased across increasing quartiles of FT in men (p for trend <0.01) and women (p for trend <0.0001). Adjustment for FT markedly attenuated the association between sex/hormone status and NT-proBNP concentrations., Conclusions: These findings suggest that lower levels of circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP concentrations in women., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification., Background: Traditional atherosclerosis risk factors have been associated with aortic and mitral valve calcium in cross-sectional studies, but long-term prospective data are lacking., Methods: This was a prospective, community-based cohort study with 27-year follow-up (median follow-up 26.9 years; range 23.1 to 29.6 years). Participants from the Framingham Offspring Study (n = 1,323, enrolled between 1971 and 1975, mean age at enrollment 34 +/- 9 years; 52% women) underwent cardiac multidetector computed tomography assessment between 2002 and 2005. Associations between the long-term average of each cardiovascular risk factor and valve calcium were estimated using logistic regression., Results: Aortic valve calcium was present in 39% of participants and mitral valve calcium in 20%. In multivariable models, the odds ratio for aortic valve calcium associated with every SD increment in long-term mean total cholesterol was 1.74 (p < 0.0001); with every SD increment in high-density lipoprotein cholesterol, it was 0.77 (p = 0.002); and with every 9 cigarettes smoked per day, it was 1.23 (p = 0.002). Associations of similar magnitude were seen for mitral valve calcium. The mean of 3 serum C-reactive protein measurements was associated with mitral valve calcium (odds ratio: 1.29 per SD increment in C-reactive protein levels; p = 0.002). A higher Framingham risk score in early adulthood (40 years age or younger) was associated with increased prevalence and severity of aortic valve calcium measured 3 decades later., Conclusions: Exposure to multiple atherosclerotic risk factors starting in early to mid-adulthood is associated with aortic and mitral valve calcium. Studies evaluating early risk factor modification to reduce the burden of valve disease are warranted.

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.

Objectives: We sought to determine whether impaired fasting glucose (IFG) predicts cardiovascular disease (CVD) events., Background: It is unclear which glucose threshold should define prediabetes. We compared the 1997 and 2003 American Diabetes Association (ADA) definitions of IFG to predict CVD., Methods: Framingham offspring participants free of CVD, categorized by the 1997 ADA IFG definition (fasting plasma glucose 110 to 125 mg/dl; 6.1 to 6.9 mmol/l) or the 2003 definition (100 to 125 mg/dl; 5.6 to 6.9 mmol/l), were followed from 1983 to 2004. Pooled logistic regression was used to calculate multivariable-adjusted odds ratios (ORs) for incident coronary heart disease (CHD; 291 events) or CVD (423 events)., Results: Four-year CHD event rates among women were 1.3% (100 to 109 mg/dl), 2.3% (110 to 125 mg/dl), and 2.9% (diabetes); whereas corresponding rates in men were 2.9%, 3.0%, and 8.7%. For the 2003 IFG definition, the OR for CHD among women was 1.7 (95% confidence interval [CI] 1.0 to 3.0, p = 0.048), whereas for the 1997 IFG definition, the OR for CHD in women was 2.2 (95% CI 1.1 to 4.4, p = 0.02), which was almost as high as for women with diabetes (OR 2.5, 95% CI 1.2 to 5.2, p = 0.01). For CVD, only the 1997 IFG definition yielded significantly greater odds of CVD in women (OR 2.1, 95% CI 1.2 to 3.6, p = 0.01). Men were not at increased odds of developing CVD or CHD by either definition., Conclusions: In women, both IFG definitions were associated with increased CHD risk, whereas neither IFG definition identified men at increased short-term risk for CHD or CVD. The finding that women with FPG 110 to 125 mg/dl had similar CHD risk compared with women with diabetes suggests that CHD risk in women may be elevated at a lower glucose level than for men.

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.

Objectives: We sought to determine the clinical factors and heritability associated with inflammation measured as circulating levels of soluble-intercellular adhesion molecule-1 (sICAM-1) in a community-based cohort., Background: Several prospective studies indicate that circulating sICAM-1 is predictive of future cardiovascular events. However, in some studies this predictive value is lost after multivariable adjustment for traditional cardiovascular disease (CVD) risk factors. We addressed the heritability of sICAM-1 and its relation to CVD risk factors in a community-based cohort., Methods: We examined 3,295 subjects from the Framingham Heart Study and measured sICAM-1 levels. We then used linear and stepwise multivariable regression to determine predictors or sICAM-1 levels., Results: In age- and gender-adjusted regression models, increased sICAM-1 levels were positively associated with age, total/high-density lipoprotein cholesterol, systolic blood pressure, body mass index (BMI), blood glucose, diabetes, smoking, and prevalent CVD. In stepwise multivariable regression models, sICAM-1 levels remained associated with age, female gender, total/high-density lipoprotein cholesterol ratio, BMI, blood glucose, smoking, and prevalent CVD. The residual heritability of sICAM-1 was 24%., Conclusions: In addition to prevalent CVD, established CVD risk factors and non-traditional ones such as BMI were associated with systemic inflammation as determined by sICAM-1 levels. There also is significant heritability of sICAM-1, which suggests a genetic component to systemic inflammation.

Objectives: The purpose of this study was to assess the relative proportions of normal versus impaired left ventricular (LV) systolic function among persons with congestive heart failure (CHF) in the community and to compare their long-term mortality during follow-up., Background: Several hospital-based investigations have reported that a high proportion of subjects with CHF have normal LV systolic function. The prevalence and prognosis of CHF with normal LV systolic function in the community are not known., Methods: We evaluated the echocardiograms of 73 Framingham Heart Study subjects with CHF (33 women, 40 men, mean age 73 years) and 146 age- and gender-matched control subjects (nested case-control study). Impaired LV systolic function was defined as an LV ejection fraction (LVEF) <0.50., Results: Thirty-seven CHF cases (51%) had a normal LVEF; 36 (49%) had a reduced LVEF. Women predominated in the former group (65%), whereas men constituted 75% of the latter group. During a median follow-up of 6.2 years, CHF cases with normal LVEF experienced an annual mortality of 8.7% versus 3.0% for matched control subjects (adjusted hazards ratio = 4.06, 95% confidence interval 1.61 to 10.26). Congestive heart failure cases with reduced LVEF had an annual mortality of 18.9% versus 4.1% for matched control subjects (adjusted hazards ratio = 4.31, 95% confidence interval 1.98 to 9.36)., Conclusions: Normal LV systolic function is often found in persons with CHF in the community and is more common in women than in men. Although CHF cases with normal LVEF have a lower mortality risk than cases with reduced LVEF, they have a fourfold mortality risk compared with control subjects who are free of CHF.

Numerous reports suggest that about one-third of patients with congestive heart failure do not have any abnormality of left ventricular systolic function. These patients presumably have heart failure on the basis of ventricular diastolic dysfunction. Our objective was to develop a comprehensive overview of published reports of the prevalence, clinical features and prognosis of diastolic heart failure and to offer recommendations for future studies. Thirty-one studies of patients with congestive heart failure with normal left ventricular systolic function were published in the time period from January 1970 through March 1995. These studies were identified with the use of computer-based searches in relevant data bases. Among patients with congestive heart failure, the prevalence of normal ventricular systolic performance in the published reports varies widely from 13% to 74%; the reported annual mortality rate also varies from 1.3% to 17.5%. The criteria for congestive heart failure, its chronicity and the age of the study sample affect the reported prevalence and prognosis of the disorder. The clinical signs and symptoms of diastolic heart failure are similar to those of patients with systolic heart failure, underscoring the need for evaluation of ventricular systolic function in patients with congestive heart failure. In the absence of any large-scale randomized clinical trial targeting these patients, the optimal treatment of diastolic heart failure is unclear. We conclude that the heterogeneity in previous studies of diastolic heart failure hinders the comparison of published reports. There is a need to conduct prospective, community-based investigations to better characterize the incidence, prevalence and natural history of diastolic heart failure. Randomized clinical trials are needed to determine optimal treatment strategies.

Objectives: Our objective was to compare the Doppler pressure half-time, Doppler continuity equation and two-dimensional echocardiographic planimetric methods of estimating mitral valve area in Lutembacher syndrome., Background: Fluid dynamics theory predicts that mitral pressure half-time varies inversely with mitral valve area and directly with net chamber compliance and the peak early diastolic transmitral gradient in pure mitral stenosis. The effects of an atrial shunt on these interrelations have not been investigated., Methods: Correlation and agreement between mitral valve area estimates obtained by the three methods and that obtained by cardiac catheterization was ascertained in 11 patients with Lutembacher syndrome., Results: Valve areas determined by planimetry and the continuity equation method correlated and agreed well with catheterization measurements (r = 0.83 and 0.81, respectively). The pressure half-time method consistently overestimated mitral valve area; the extent of overestimation was greater in patients with larger atrial shunts. The hemodynamic pressure half-time was independent of the mitral valve area, chamber compliance and the peak transmitral gradient. It was dependent on the magnitude of the atrial shunt, although the correlation obtained was only fair (r = 0.61)., Conclusions: These findings suggest that the Doppler pressure half-time method is an inaccurate measure of mitral valve area whenever an atrial shunt coexists with mitral stenosis. Planimetry and the Doppler continuity equation methods yield accurate estimates of mitral valve area in Lutembacher syndrome.