- [Show abstract] [Hide abstract] ABSTRACT: Background-Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. Methods and Results-The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68±6% versus 64±7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and height-indexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population. Conclusions-We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes.
- [Show abstract] [Hide abstract] ABSTRACT: Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. We related objective measures of moderate- to vigorous-intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid-femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10-minute increment) were associated with lower carotid-femoral pulse wave velocity (estimate -0.53 ms/m; P=0.006) and lower forward pressure wave (estimate -0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with loge left ventricular mass (estimate 0.006 loge [g/m(2)]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. In our community-based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
- [Show abstract] [Hide abstract] ABSTRACT: We examined the relation between objectively measured physical activity with accelerometry and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based sample. We evaluated 1249 participants of the Framingham Third Generation and Omni II cohorts (mean age 51.7 years, 47% women) who underwent assessment of moderate-to-vigorous physical activity (MVPA) with accelerometry over 5 to 7 days, and multi-detector computed tomography for measurement of SAT and VAT volume; fat attenuation was estimated by SAT and VAT hounsfield units (HU). In women, higher levels of MVPA were associated with decreased SAT (P<0.0001) and VAT volume (P<0.0001). The average decrement in VAT per 30 minute/day increase in MVPA was -453 cm(3) (95% CI -574, -331). The association was attenuated but persisted upon adjustment for BMI (-122 cm(3), P=0.002). Higher levels of MVPA were associated with higher SAT HU (all P≤0.01), a marker of fat quality, even after adjustment for SAT volume. Similar findings were observed in men but the magnitude of the association was less. Sedentary time was not associated with SAT or VAT volume or quality in men or women. MVPA was associated with less VAT and SAT and better fat quality. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
- [Show abstract] [Hide abstract] ABSTRACT: PurposeTo determine normative values for left ventricular (LV) volumes, mass, concentricity, and ejection fraction (EF) and investigate associations between sex, age, and body size with LV parameters in community-dwelling adults.Materials and Methods In all, 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice cine steady-state free precession MR of the left ventricle; from these a healthy referent group (n = 852, 61 ± 9 years, 40% men) free of clinical cardiac disease and hypertension (SBP < 140, DBP < 90 mmHg, never used antihypertensive medication ≥30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (≤55, 56–65, >65 years); LV parameters were indexed to measures of body size.ResultsMen have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (P < 0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, although indexation attenuates this association. LVEF is greater in women than men (68 ± 5% vs. 66 ± 5%, P < 0.01) and increases with age in both sexes (P < 0.05).Conclusion Among nonhypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.
- [Show abstract] [Hide abstract] ABSTRACT: The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose: Whereas greater physical activity (PA) is known to prevent cardiovascular disease (CVD), the relative importance of performing PA in sustained bouts of activity versus shorter bouts of activity on CVD risk is not known. The objective of this study was to investigate the relationship between moderate-to-vigorous PA (MVPA), measured in bouts ≥10 and <10 min, and CVD risk factors in a well-characterized community-based sample of white adults. Methods: We conducted a cross-sectional analysis of 2109 participants in the Third Generation Cohort of the Framingham Heart Study (mean age = 47 yr, 55% women) who underwent objective assessment of PA by accelerometry over 5-7 d. Total MVPA, MVPA done in bouts ≥10 min (MVPA(10+)), and MVPA done in bouts <10 min (MVPA(<10)) were calculated. MVPA exposures were related to individual CVD risk factors, including measures of adiposity and blood lipid and glucose levels, using linear and logistic regression. Results: Total MVPA was significantly associated with higher HDL levels and with lower triglycerides, BMI, waist circumference, and Framingham risk score (P < 0.0001). MVPA(<10) showed similar statistically significant associations with these CVD risk factors (P < 0.001). Compliance with national guidelines (≥150 min of total MVPA) was significantly related to lower BMI, triglycerides, Framingham risk score, waist circumference, higher HDL, and a lower prevalence of obesity and impaired fasting glucose (P < 0.001 for all). Conclusions: Our cross-sectional observations on a large middle-age community-based sample confirm a positive association of MVPA with a healthier CVD risk factor profile and indicate that accruing PA in bouts <10 min may favorably influence cardiometabolic risk. Additional investigations are warranted to confirm our findings.
- [Show abstract] [Hide abstract] ABSTRACT: We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass.
- [Show abstract] [Hide abstract] ABSTRACT: The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 ± 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin A1c, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score >100 were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF.
- [Show abstract] [Hide abstract] ABSTRACT: Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. A total of 1603 Framingham Heart Study Offspring participants (age, 64+/-9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht(2.7) and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.
- [Show abstract] [Hide abstract] ABSTRACT: Extensive efforts have been aimed at understanding the genetic underpinnings of complex diseases that affect humans. Numerous genome-wide association studies have assessed the association of genes with human disease, including the Framingham Heart Study (FHS), which genotyped 550,000 SNPs in 9,000 participants. The success of such efforts requires high rates of consent by participants, which is dependent on ethical oversight, communications, and trust between research participants and investigators. To study this we calculated percentages of participants who consented to collection of DNA and to various uses of their genetic information in two FHS cohorts between 2002 and 2009. The data included rates of consent for providing a DNA sample, creating an immortalized cell line, conducting research on various genetic conditions including those that might be considered sensitive, and for notifying participants of clinically significant genetic findings were above 95%. Only with regard to granting permission to share DNA or genetic findings with for-profit companies was the consent rate below 95%. We concluded that the FHS has maintained high rates of retention and consent for genetic research that has provided the scientific freedom to establish collaborations and address a broad range of research questions. We speculate that our high rates of consent have been achieved by establishing frequent and open communications with participants that highlight extensive oversight procedures. Our approach to maintaining high consent rates via ethical oversight of genetic research and communication with study participants is summarized in this report and should be of help to other studies engaged in similar types of research. Published 2010 Wiley-Liss, Inc.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to investigate the impact of age, sex, and hypertension (HTN) on aortic atherosclerotic burden using cardiovascular MRI (CMR) in a free-living longitudinally followed cohort. 1763 participants (829 M and 934 F; 38 to 88 years of age) of the Framingham Heart Study Offspring cohort underwent CMR of the thoracoabdominal aorta using an ECG-gated 2D T2-weighted black-blood sequence. Of these, 1726 subjects (96%) with interpretable CMR were characterized by sex, age-quartile, and presence or absence of HTN and clinical cardiovascular disease (CVD). Aortic plaque prevalence and volume increased with increasing age in both sexes. For the nonhypertensive (no-HTN) group, plaque was identified in 702 (46%) with greater prevalence in women than in men (P<0.006). HTN was associated with greater aortic plaque burden (P<0.02). The 200 subjects with clinical CVD had greater plaque burden than subjects without CVD (P<0.0001). In this free-living longitudinally followed cohort, subclinical aortic atherosclerosis was seen in nearly half of subjects and increased with advancing age. HTN was associated with increased aortic plaque burden. Among no-HTN subjects, women had greater plaque burden than men. These data suggest that subclinical atherosclerosis is more common in no-HTN women and emphasize the importance of focusing on preventive measures in both sexes.
- [Show abstract] [Hide abstract] ABSTRACT: Atrial fibrillation (AF) is a major risk factor for stroke. Although acute alcohol intake has been associated with AF, it is not known whether long-term alcohol consumption in moderation is associated with an increased risk of AF. We used a risk set method to assess the relation of long-term alcohol consumption to the risk of AF among participants in the Framingham Study. For each case, up to 5 controls were selected and matched for age, age at baseline examination, sex, cohort, baseline history of hypertension, congestive heart failure, and myocardial infarction. Within each risk set, alcohol consumption was averaged from baseline until the examination preceding the index case of AF. Of the 1,055 cases of AF occurring during a follow-up of >50 years, 544 were men and 511 were women. In a conditional logistic regression with additional adjustment for systolic blood pressure, age at baseline examination, education, and cumulative history of myocardial infarction, congestive heart failure, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease, the relative risks were 1.0 (reference), 0.97 (95% confidence interval [CI] 0.78 to 1.22), 1.06 (95% CI 0.80 to 1.38), 1.12 (95% CI 0.80 to 1.55), and 1.34 (95% CI 1.01 to 1.78) for alcohol categories of 0, 0.1 to 12, 12.1 to 24, 24.1 to 36, and >36 g/day, respectively. In conclusion, our data indicate little association between long-term moderate alcohol consumption and the risk of AF, but a significantly increased risk of AF among subjects consuming >36 g/day (approximatively >3 drinks/day).
National Heart, Lung, and Blood Institute
베서스다, Maryland, United States
- Division of Cardiovascular Sciences (DCVS)