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ABSTRACT: Increased arterial stiffness and wave reflection have been identified as cardiovascular disease risk factors. In light of significant sex differences and the moderate heritability of vascular function measures, we hypothesized that variation in the genes coding for oestrogen receptors alpha (ESR1) and beta (ESR2) and aromatase (CYP19A1) is associated with aortic stiffness and pressure wave reflection as measured by non-invasive arterial tonometry. In all, 1261 unrelated Framingham Offspring Study participants who attended the seventh examination cycle (mean age 62+/-10 years, 52% women) and had arterial tonometry and genotyping data were included in the study. Analysis of covariance was used to assess the association of polymorphisms with forward wave amplitude, augmented pressure, augmentation index (AI), carotid-femoral pulse wave velocity and mean arterial pressure with adjustment for potential confounders. In the sex-pooled analysis, those homozygous for the minor allele at any of four ESR1 variants that were in strong linkage disequilibrium ((TA)(n), rs2077647, rs2234693 and rs9340799) had on an average 18% higher augmented pressure and 16% greater AI compared with carriers of one or two major alleles (P=0.0002-0.01). A similar magnitude of association was detected in those homozygous for the common allele at two ESR2 single-nucleotide polymorphisms (P=0.007-0.02). Our results are consistent with the hypothesis that variation in ESR1 and ESR2, but not CYP19A1, is associated with an increased wave reflection that may contribute to associations between these variants and adverse clinical events demonstrated earlier. Our findings will need to be replicated in additional cohorts.
Journal of human hypertension 03/2009; 23(10):636-44. · 2.80 Impact Factor
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ABSTRACT: P-selectin is a cell adhesion molecule that is involved in atherogenesis, and soluble concentrations of this biomarker reflect cardiovascular risk. However, the clinical correlates and genetic characterization of soluble P-selectin have not been clearly elucidated.
To describe clinical and genetic correlates of circulating P-selectin in the community.
In Framingham Heart Study Offspring (European descent) and Omni (ethnic/racial minority) participants, we examined the association of cardiovascular risk factors with soluble P-selectin concentrations. In Offspring participants, we evaluated heritability, linkage and association of 29 SELP single-nucleotide polymorphisms (SNPs) with adjusted P-selectin concentrations.
In multivariable analysis of 3,690 participants (54% women, mean age 60 +/- 10 years), higher log-transformed P-selectin concentrations were inversely associated with female sex and hormone replacement therapy, and positively associated with age, ethnic/racial minority status, cigarette smoking, waist circumference, systolic blood pressure, fasting glucose, and total/high-density lipoprotein cholesterol and triglyceride concentrations. Clinical factors explained 10.4% of the interindividual variability in P-selectin concentrations. In 571 extended pedigrees (n = 1,841) with >or= 2 phenotyped members per family, multivariable-adjusted heritability was 45.4 +/- 5.8%. Among the SELP SNPs examined, a non-synonymous SNP (rs6136) encoding a threonine-to-proline substitution at position 715 was highly significantly associated with decreased P-selectin concentrations (P = 5.2 x 10(-39)), explaining 9.7% of variation after adjustment for clinical factors.
Multiple clinical factors and an SNP in the SELP gene were significantly associated with circulating P-selectin concentrations. One SNP in SELP explained significant variation in circulating P-selectin concentrations, even after accounting for known clinical correlates.
Journal of Thrombosis and Haemostasis 02/2008; 6(1):20-31. · 5.73 Impact Factor
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M K Shea, E J Benjamin,
J Dupuis,
J M Massaro,
P F Jacques,
R B D'Agostino,
J M Ordovas,
C J O'Donnell,
B Dawson-Hughes,
R S Vasan,
S L Booth
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ABSTRACT: Objective: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women.
European Journal of Clinical Nutrition 11/2007; 63(4):458-464. · 2.46 Impact Factor
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M K Shea, E J Benjamin,
J Dupuis,
J M Massaro,
P F Jacques,
R B D'Agostino,
J M Ordovas,
C J O'Donnell,
B Dawson-Hughes,
R S Vasan,
S L Booth
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ABSTRACT: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women.
A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR).
Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance.
Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.
European journal of clinical nutrition 11/2007; 63(4):458-64. · 3.07 Impact Factor
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Z S Tan,
A S Beiser,
R S Vasan,
R Roubenoff,
C A Dinarello,
T B Harris, E J Benjamin,
R Au,
D P Kiel,
P A Wolf,
S Seshadri
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ABSTRACT: To examine whether serum cytokines and spontaneous production of peripheral blood mononuclear cell (PBMC) cytokines are associated with the risk of incident Alzheimer disease (AD).
We followed 691 cognitively intact community-dwelling participants (mean age 79 years, 62% women) and related PBMC cytokine production (tertiles of spontaneous production of interleukin 1 [IL-1], IL-1 receptor antagonist, and tumor necrosis factor alpha [TNF-alpha]) and serum C-reactive protein and interleukin 6 (IL-6) to the risk of incident AD.
Adjusting for clinical covariates, individuals in the top two tertiles (T2 and T3) of PBMC production of IL-1 or the top tertile (T3) of PBMC production of TNF-alpha were at increased risk of developing AD (multivariable-adjusted hazard ratio [HR] for IL-1 T2 = 2.84, 95% CI 1.09 to 7.43; p = 0.03 and T3 = 2.61, 95% CI 0.96 to 7.07; p = 0.06; for TNF-alpha, adjusted HR for T2 = 1.30, 95% CI 0.53 to 3.17; p = 0.57 and T3 = 2.59, 95% CI 1.09 to 6.12; p = 0.031]) compared with those in the lowest tertile (T1). Interpretation: Higher spontaneous production of interleukin 1 or tumor necrosis factor alpha by peripheral blood mononuclear cells may be a marker of future risk of Alzheimer disease (AD) in older individuals. These data strengthen the evidence for a pathophysiologic role of inflammation in the development of clinical AD.
Neurology 06/2007; 68(22):1902-8. · 8.31 Impact Factor
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A L Jefferson,
J M Massaro,
P A Wolf,
S Seshadri,
R Au,
R S Vasan,
M G Larson,
J B Meigs,
J F Keaney,
I Lipinska,
S Kathiresan, E J Benjamin,
C DeCarli
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ABSTRACT: Systemic inflammation is associated with ischemia and Alzheimer disease (AD). We hypothesized that inflammatory biomarkers would be associated with neuroimaging markers of ischemia (i.e., white matter hyperintensities [WMH]) and AD (i.e., total brain volume [TCB]).
MRI WMH and TCB were quantified on 1,926 Framingham Offspring participants free from clinical stroke, TIA, or dementia (mean age 60 +/- 9 years; range 35 to 85 years; 54% women) who underwent measurement of a circulating inflammatory marker panel, including CD40 ligand, C-reactive protein, interleukin-6 (IL-6), soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, myeloperoxidase, osteoprotegerin (OPG), P-selectin, tumor necrosis factor-alpha (TNFalpha), and tumor necrosis factor receptor II. To account for head size, both TCB (TCBV) and WMH (WMH/TCV) were divided by total cranial volume. We used multivariable linear regression to relate 10 log-transformed inflammatory biomarkers to brain MRI measures.
In multivariable models, inflammatory markers as a group were associated with TCBV (p < 0.0001) but not WMH/TCV (p = 0.28). In stepwise models adjusted for clinical covariates with backwards elimination of markers, IL-6 and OPG were inversely associated with TCBV; TNFalpha was inversely related to TCBV in a subset of 1,430 participants. Findings were similar in analyses excluding individuals with prevalent cardiovascular disease. The relations between TCBV and inflammatory markers were modified by both sex and age, and generally were more pronounced in men and in older individuals.
Although our observational cross-sectional data cannot establish causality, they are consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age.
Neurology 04/2007; 68(13):1032-8. · 8.31 Impact Factor
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Heart (British Cardiac Society) 11/2006; 92(10):1514-5. · 4.22 Impact Factor
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S Demissie,
D Levy, E J Benjamin,
L A Cupples,
J P Gardner,
A Herbert,
M Kimura,
M G Larson,
J B Meigs,
J F Keaney,
A Aviv
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ABSTRACT: Insulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40-89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age (r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r =-0.16, P = 0.007) and urinary 8-epi-PGF(2alpha) (r = -0.16, P = 0.005) - an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 +/- 0.042 kb, normotensives = 6.07 +/- 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance.
Aging Cell 08/2006; 5(4):325-30. · 6.26 Impact Factor
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ABSTRACT: Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%), and twofold higher (95% CI 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles <0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage.
Kidney International 07/2006; 69(11):2064-9. · 6.61 Impact Factor
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ABSTRACT: The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.
American Journal of Respiratory and Critical Care Medicine 09/2001; 164(6):933-8. · 11.08 Impact Factor
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New England Journal of Medicine 02/2001; 344(1):56-9. · 53.30 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is strongly associated with thromboembolic complications, although the mechanism for the increased risk has not been fully explained. To determine whether AF might be associated with a hypercoagulable state, we studied hemostatic factors in subjects with or without AF in the Framingham Heart Study. In 3,577 subjects, we measured fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor-1 antigen. Forty-seven subjects had AF at the index clinic examination and 15 had AF on a prior examination, but not on the current examination. Before matching, the 47 subjects with prevalent AF had higher levels of fibrinogen, von Willebrand factor, and tPA antigen than those without AF, all p < or =0.03. Compared with 167 referent subjects matched for age, sex, and other risk factors, those with AF had higher tPA antigen levels than those without AF, 1 1.8 +/- 4.0 ng/ml versus 10.5 +/- 3.9 ng/ml (p = 0.04). However, when further stratified according to their cardiovascular disease status, the differences in hemostatic factors were no longer significant. We conclude that the prothrombotic profile associated with AF was explained by the risk factors of the subjects and the presence of cardiovascular disease. Nonetheless, the hemostatic changes may contribute toward the propensity for thromboembolic complications in AF. Further prospective studies are needed to evaluate whether measurement of these and other hemostatic factors will identify patients with AF who are at increased risk for thromboembolic complications, and who may therefore benefit from more intensive therapy.
The American Journal of Cardiology 01/2001; 87(2):168-71. · 3.37 Impact Factor
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ABSTRACT: The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term care settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body mass index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2. 30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or an elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope.
The American Journal of Cardiology 06/2000; 85(10):1189-93. · 3.37 Impact Factor
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ABSTRACT: Although echocardiography is used extensively in clinical medicine, guidelines for quantitative interpretation of echocardiographic measurements are unavailable. The goals of this investigation were to provide an overview of scientific standards for formulating reference values, with clinical chemistry used as a model, to evaluate published echocardiographic reference limits, to survey clinical echocardiography laboratories regarding their interpretation of echocardiographic measurements, and to provide recommendations for improving the interpretation and reporting of echocardiographic measurements.
We reviewed the original reports of the International Federation of Clinical Chemistry on guidelines for formulating reference values. We obtained published reports on echocardiographic reference limits through searches of electronic databases supplemented by a manual search of relevant bibliographies. We also surveyed echocardiographic laboratories in 35 adult acute-care hospitals in Eastern Massachusetts. Studies on echocardiographic reference values were evaluated with the use of guidelines from clinical chemistry. Responses from the 29 participating echocardiographic laboratories were evaluated for their practice of quantitative echocardiographic interpretation. There is considerable heterogeneity in the echocardiographic reference values available in the literature. There is also a lack of agreement in the literature and among echocardiographers regarding the partitioning of reference values (by sex, ethnicity, or age), the anthropometric measure to be used for indexation, and the choice of cut-points for categorizing values within the abnormal range.
We advocate that echocardiographic reference limits be standardized and a consensus generated regarding the partitioning of reference limits and the indexation of echocardiographic measurements. Such measures can aid in quantitative echocardiographic interpretation and render the results more scientific and consistent.
American Heart Journal 04/2000; 139(3):412-22. · 4.65 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting an estimated 2.2 million adults in the United States. The median age of people with AF is 75, and it affects 8.8% of the US population > 80 years of age. Prevalence data from other countries are presented. Direct comparisons are limited by study design, but rough comparisons suggest that the prevalence of AF in Europe is similar to the prevalence in the United States, whereas the prevalence in Asia may be lower. The limited comparative data underscore our lack of understanding of AF risk factors and complications in racial subgroups and in developing countries. AF increases stroke risk 5-fold. The clinical features that predict higher risk of stroke in AF are prior stroke, hypertension, advancing age, diabetes, and congestive heart failure. Predicting which patients with atrial fibrillation are at the highest risk of stroke remains a challenge. Echocardiographic findings have been investigated to assist in the risk stratification of patients with AF. Despite evidence from clinical trials that anticoagulation with warfarin reduces stroke incidence and even mortality, anticoagulation remains underutilized, especially in the elderly. Improvement in the rate of anticoagulation in patients with AF at risk of stroke can be expected to decrease the complications and mortality of AF.
The American Journal of Cardiology 11/1999; 84(9A):131R-138R. · 3.37 Impact Factor
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ABSTRACT: Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study.
Classic mitral-valve prolapse was defined as superior displacement of the mitral leaflets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm.
A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild.
In a community based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low.
New England Journal of Medicine 08/1999; 341(1):1-7. · 53.30 Impact Factor
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ABSTRACT: 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.
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.
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.
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).
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.
Journal of the American College of Cardiology 06/1999; 33(7):1948-55. · 14.16 Impact Factor
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ABSTRACT: Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9 years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m2; 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs.
The American Journal of Cardiology 04/1999; 83(6):897-902. · 3.37 Impact Factor
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ABSTRACT: The prevalence, prognosis, and predictors of left ventricular hypertrophy (LVH) are reviewed, and theories of the pathogenesis of the relation between LVH and poor prognosis are summarized to highlight controversies in the field. In the Framingham Heart Study, which consists largely of white people, echocardiographic LVH has a prevalence of 14% in men and 18% in women. The prevalence of LVH is reported to be elevated in African Americans compared with whites, although the higher prevalence has been attributed to the increased prevalence of hypertension and obesity. Echocardiographic LVH is independently associated with a variety of cardiovascular endpoints, including coronary heart disease and stroke. Furthermore, after adjusting for other cardiovascular disease risk factors, LVH is associated with a doubling in mortality in both white and African American cohorts. Despite the intensive investigation of LVH, there remain many unanswered questions: To what extent do genetic or other factors account for the large portion of the variance in LVH that remains unexplained? What is the prognosis of LVH and left ventricular geometry in a population-based African American cohort? How does the development and progression of LVH relate to other risk factors and their treatment? What is the relation of LVH to poor prognosis? The proposed Jackson Heart Study will help address many important unanswered questions regarding LVH.
The American Journal of the Medical Sciences 04/1999; 317(3):168-75. · 1.39 Impact Factor
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ABSTRACT: This study examined the relations of echocardiographically determined left ventricular (LV) mass and hypertrophy to the risk of sudden death.
Echocardiographic LV hypertrophy is associated with increased risk for all-cause mortality and cardiovascular disease morbidity and mortality. However, little is known about the association of echocardiographic LV hypertrophy with sudden death.
We examined the relations of LV mass and hypertrophy to the incidence of sudden death in 3,661 subjects enrolled in the Framingham Heart Study who were > or =40 years of age. The baseline examination was performed from 1979 to 1983 and LV hypertrophy was defined as LV mass (adjusted for height) > 143 g/m in men and > 102 g/m in women. During up to 14 years of follow-up there were 60 sudden deaths. Cox models examined the relations of LV mass and LV hypertrophy to sudden death risk after adjusting for known risk factors.
The prevalence of LV hypertrophy was 21.5%. The risk factor-adjusted hazard ratio (HR) for sudden death was 1.45 (95% confidence interval [CI] 1.10 to 1.92, p=0.008) for each 50-g/m increment in LV mass. For LV hypertrophy, the risk factor-adjusted HR for sudden death was 2.16 (95% CI 1.22 to 3.81, p=0.008). After excluding the first 4 years of follow-up, both increased LV mass and LV hypertrophy conferred long-term risk of sudden death (HR 1.53, 95% CI 1.01 to 2.28, p=0.047 and HR 3.28, 95% CI 1.58 to 6.83, p=0.002, respectively).
Increased LV mass and hypertrophy are associated with increased risk for sudden death after accounting for known risk factors.
Journal of the American College of Cardiology 11/1998; 32(5):1454-9. · 14.16 Impact Factor
