Dataset Information

Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study.

ABSTRACT: Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited.We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001).Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF.

SUBMITTER: Lam CS

PROVIDER: S-EPMC3785074 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study.

Lam Carolyn S P CS Liu Xuan X Yang Qiong Q Larson Martin G MG Pencina Michael J MJ Aragam Jayashri J Redfield Margaret M MM Benjamin Emelia J EJ Vasan Ramachandran S RS

Circulation. Cardiovascular genetics 20100930 6

<h4>Background</h4>Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited.<h4>Methods and results</h4>We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th pe ...[more]

PMID: 20884845

Similar Datasets

Project description:OBJECTIVES:The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation. BACKGROUND:Temporal trends in the prevalence and management of major risk factors may affect the epidemiology of HF. METHODS:We compared the frequency, correlates, and prognosis of LVSD (left ventricular ejection fraction [LVEF] <50%) among Framingham Study participants without and with clinical HF in 3 decades (1985 to 1994, 1995 to 2004, and 2005 to 2014). RESULTS:Among participants without HF (12,857 person-observations, mean age 53 years, 56% women), the prevalence of LVSD on echocardiography decreased (3.38% in 1985 to 1994 vs. 2.2% in 2005 to 2014; p < 0.0001), whereas mean LVEF increased (65% vs. 68%; p < 0.001). The elevated risk associated with LVSD (?2- to 4-fold risk of HF or death) remained unchanged over time. Among participants with new-onset HF (n = 894, mean age 75 years, 52% women), the frequency of heart failure with preserved ejection fraction (HFpEF) increased (preserved LVEF ?50%: 41.0% in 1985 to 1994 vs. 56.17% in 2005 to 2014; p < 0.001) and heart failure with reduced ejection fraction (HFrEF) decreased (reduced LVEF <40%: 44.10% vs. 31.06%; p = 0.002), whereas heart failure with midrange LVEF remained unchanged (LVEF 40% to <50%: 14.90% vs. 12.77%; p = 0.66). Cardiovascular mortality associated with HFrEF declined across decades (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.97), but remained unchanged for heart failure with midrange LVEF and HFpEF. Approximately 47% of the observed increase in LVEF among those without HF and 75% of the rising proportion of HFpEF across decades was attributable to trends in risk factors, especially a decline in the prevalence of coronary heart disease among those with HF. CONCLUSIONS:The profile of HF in the community has changed in recent decades, with a lower prevalence of LVSD and an increased frequency of HFpEF, presumably due to concomitant risk factor trends.

Project description:Osteoporosis is characterized by low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. There have been no genome-wide association and linkage studies for these traits using high-density genotyping platforms.We used the Affymetrix 100K SNP GeneChip marker set in the Framingham Heart Study (FHS) to examine genetic associations with ten primary quantitative traits: bone mineral density (BMD), calcaneal ultrasound, and geometric indices of the hip. To test associations with multivariable-adjusted residual trait values, we used additive generalized estimating equation (GEE) and family-based association tests (FBAT) models within each sex as well as sexes combined. We evaluated 70,987 autosomal SNPs with genotypic call rates > or =80%, HWE p > or = 0.001, and MAF > or =10% in up to 1141 phenotyped individuals (495 men and 646 women, mean age 62.5 yrs). Variance component linkage analysis was performed using 11,200 markers.Heritability estimates for all bone phenotypes were 30-66%. LOD scores > or =3.0 were found on chromosomes 15 (1.5 LOD confidence interval: 51,336,679-58,934,236 bp) and 22 (35,890,398-48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 x 10(-6) and 2.5 x 10(-5), respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits (including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association (FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in MTHFR; rs1884052 and rs3778099 in ESR1; rs4988300 in LRP5; rs2189480 in VDR; rs2075555 in COLIA1; rs10519297 and rs2008691 in CYP19, as well as SNPs in PPARG (rs10510418 and rs2938392) and ANKH (rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.

Dataset Information

Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study.

Publications

Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets