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BACKGROUND: In the conventional paradigm of the progression of left ventricular hypertrophy, a thick-walled left ventricle (LV) ultimately transitions to a dilated cardiomyopathy. There are scant data in humans demonstrating whether this transition occurs commonly without an interval myocardial infarction. METHODS AND RESULTS: Participants (n=1282) from the Dallas Heart Study underwent serial cardiac magnetic resonance ≈7 years apart. Those with interval cardiovascular events and a dilated LV (increased LV end-diastolic volume [EDV] indexed to body surface area) at baseline were excluded. Multivariable linear regression models tested the association of concentric hypertrophy (increased LV mass and LV mass/volume0.67) with change in LVEDV. The study cohort had a median age of 44 years, 57% women, 43% black, and 11% (n=142) baseline concentric hypertrophy. The change in LVEDV in those with versus without concentric hypertrophy was 1 mL (-9 to 12) versus -2 mL (-11 to 7), respectively, P<0.01. In multivariable linear regression models, concentric hypertrophy was associated with larger follow-up LVEDV (P≤0.01). The progression to a dilated LV was uncommon (2%, n=25). CONCLUSIONS: In the absence of interval myocardial infarction, concentric hypertrophy was associated with a small, but signifcantly greater, increase in LVEDV after 7-year follow-up. However, the degree of LV enlargement was minimal, and few participants developed a dilated LV. These data suggest that if concentric hypertrophy does progress to a dilated cardiomyopathy, such a transition would occur over a much longer timeframe (eg, decades) and may be less common than previously thought. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifer: NCT00344903. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess characteristic impedance (Zc) of the proximal aorta in young and middle-aged individuals with isolated systolic hypertension (ISH). Zc is an index of aortic stiffness relative to aortic size. In the Dallas Heart Study, 2001 untreated participants 18 to 64 years of age (mean age: 42.3 years; 44% black race) were divided into the following groups based on office blood pressure (BP) measurements: (1) optimal BP (systolic BP [SBP] <120 mm Hg and diastolic BP [DBP] <80 mm Hg; n=837); (2) prehypertension (SBP 120-139 mm Hg and DBP 80-89 mm Hg; n=821); (3) ISH (SBP ≥140 mm Hg and DBP <90 mm Hg; n=121); (4) isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg; n=44); and (5) systolic-diastolic hypertension (SBP ≥140 mm Hg and DBP ≥90 mm Hg; n=178). Zc, aortic arch pulse wave velocity, and minimum ascending aortic size were quantified using cardiovascular magnetic resonance. In multivariable-adjusted linear models, Zc was highest in the ISH group compared with the optimal BP, isolated diastolic hypertension, or systolic-diastolic hypertension groups (103.2±4.0 versus 68.3±2.1, 75.4±6.0, and 88.9±4.8 dyne*seconds/cm5, respectively; all P<0.05). The Zc-ISH association did not differ by race. Aortic pulse wave velocity was highest in the ISH group compared with the optimal BP, isolated diastolic hypertension, or systolic-diastolic hypertension groups (6.3±0.3 versus 4.3±0.1, 4.4±0.4 and 5.5±0.3 m/s, respectively; all P<0.05), whereas aortic size was similar across groups (all P>0.2). Results were similar in a subgroup of 1551 participants 18 to 49 years of age. In a multiracial population-based sample, we found evidence of a mismatch between proximal aortic stiffness and diameter in young and middle-aged adults with ISH. [ABSTRACT FROM AUTHOR]

The article presents a study which introduces the 4-tiered classification of left ventricular hypertrophy (LVH) to monitor the LV concentricity and LV end-diastolic volume (LVEDV). It states that the study was made on 2803 subjects of the Dallas Heart Study, wherein they underwent cardiac magnetic resonance imaging (MRI). It reveals that subjects with eccentric LVH can be classified into two groups such as with dilated hypertrophy and the large group with no thick of dilated hypertrophy.

The article presents a study that investigates on the association of cystatin c on the function and structure of left ventricular (LV). The study was carried out from the participants of Dallas Heart Study whose age ranges from 30 to 65 years wherein their cystatin c level and concentricity were assessed using cardiac magnetic resonance imaging (MRI). The study reveals that high level of cystatin c establish a link on the development of LV mass and hypertrophy.

To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (P<0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (P<0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (P=0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction. [ABSTRACT FROM AUTHOR]

Corin activates pro-A-type naturetic peptide and pro-B-type naturetic peptide into biologically active molecules. We recently identified a minor allele in the corin gene defined by 2 highly linked single nucleotide polymorphisms (T555I and Q568P), which was associated with hypertension in blacks. Because of the direct antihypertrophic effects of the natriuretic peptide system, we hypothesized that the minor corin I555(P568) allele would be associated with an enhanced hypertrophic response to pressure overload. The relationship between systolic blood pressure and indexed left ventricular mass, derived from cardiac MRI, was analyzed in the Dallas Heart Study as a function of corin allele status. The Multi-Ethnic Study of Atherosclerosis was used as a validation cohort. All of the analyses were limited to self-identified blacks without treatment for hypertension. In addition, we genotyped 2114 markers highly informative for African ancestry in the Dallas Heart Study and derived a covariate representing African ancestry for multivariate models. In adjusted analysis, the corin I555(P568) allele was an independent predictor of left-ventricular mass in subjects with elevated systolic blood pressure. Linear spline regression analysis confirmed a significant interaction (P=0.002) between the corin I555(P568) allele and systolic blood pressure as a predictor of left ventricular mass in subjects with systolic blood pressure >120 mm Hg, and this nonlinear interaction was replicated in the Multi-Ethnic Study of Atherosclerosis. In the Dallas Heart Study, the corin I555(P568) allele was also associated with an increased odds for prevalent left ventricular hypertrophy in the presence of untreated hypertension. These data suggest that the corin I555(P568) allele represents a cardiac hypertrophy-sensitizing genetic locus in systemic hypertension. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Coronary artery calcium scoring only represents a small fraction of all information available in noncontrast cardiac computed tomography (CAC-CT). We hypothesized that an automated pipeline using radiomics and machine learning could identify phenotypic information about high-risk left ventricular hypertrophy (LVH) embedded in CAC-CT. Methods: This was a retrospective analysis of 1982 participants from the DHS (Dallas Heart Study) who underwent CAC-CT and cardiac magnetic resonance. Two hundred twenty-four participants with high-risk LVH were identified by cardiac magnetic resonance. We developed an automated adaptive atlas algorithm to segment the left ventricle on CAC-CT, extracting 107 radiomics features from the volume of interest. Four logistic regression models using different feature selection methods were built to predict high-risk LVH based on CAC-CT radiomics, sex, height, and body surface area in a random training subset of 1587 participants. Results: The respective areas under the receiver operating characteristics curves for the cluster-based model, the logistic regression model after exclusion of highly correlated features, and the penalized logistic regression models using least absolute shrinkage and selection operators with minimum or one SE λ values were 0.74 (95% CI, 0.67–0.82), 0.74 (95% CI, 0.67–0.81), 0.76 (95% CI, 0.69–0.83), and 0.73 (95% CI, 0.66–0.80) for detecting high-risk LVH in a distinct validation subset of 395 participants. Conclusions: Ventricular segmentation, radiomics features extraction, and machine learning can be used in a pipeline to automatically detect high-risk phenotypes of LVH in participants undergoing CAC-CT, without the need for additional imaging or radiation exposure. Registration: URL http://www.clinicaltrials.gov. Unique identifier: NCT00344903. [ABSTRACT FROM AUTHOR]

Background: Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders., Methods and Results: Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men., Conclusions: Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.

Objective: The purpose of this study was to evaluate the associations between plasma levels of soluble CD40 ligand (sCD40L), atherosclerosis risk factors, and evidence of subclinical atherosclerosis., Methods and Results: Plasma levels of sCD40L were measured in 2811 subjects from the Dallas Heart Study, a multiethnic population-based cross-sectional study. Electron Beam Computed Tomography measurements of coronary artery calcium (CAC) and MRI measurements of aortic plaque were performed in 2198 and 1965 subjects, respectively. No association was observed between quartiles of sCD40L and age, sex, race, body mass index, diabetes, smoking, creatinine clearance, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or C-reactive protein. In contrast, weak but statistically significant associations were observed between sCD40L and total cholesterol and triglycerides. The prevalence of detectable CAC (CAC score > or =10) and aortic plaque did not differ across sCD40L quartiles, and individuals with CAC scores <10, > or =10 to 100, >100 to 400, and >400 had similar sCD40L levels., Conclusions: In a large and representative multiethnic population-based sample, sCD40L was not associated with most atherosclerotic risk factors or with subclinical atherosclerosis. These findings suggest that sCD40L will not be useful as a tool to screen for the presence of subclinical atherosclerosis in the population. Further evaluation of this biomarker should focus on settings in which platelet activation is common, such as following acute coronary syndromes or coronary revascularization procedures.

Background: Elevated plasma levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease in whites. Blacks have 2- to 3-fold higher plasma levels of Lp(a) than whites and yet do not have a correspondingly higher rate of coronary events. It remains unclear whether elevated plasma levels of Lp(a) are an independent risk factor for coronary atherosclerosis in individuals of African descent., Methods and Results: The relationship between plasma levels of Lp(a), apolipoprotein(a) isoform sizes, and the presence of coronary calcium was examined in 761 blacks and 527 whites (men aged >40 years, women aged >45 years) from a population-based sample. No relationship was found between plasma levels of Lp(a), apolipoprotein(a) isoform size, or a combination of these 2 variables and coronary artery calcium (CAC) in whites or blacks. No correlation was observed between plasma levels of Lp(a) and coronary calcium scores in any group, although all black men with very high plasma levels of Lp(a) (>300 micromol/L; n=7) were CAC-positive. Whites with high plasma levels of Lp(a) plus elevated plasma levels of LDL cholesterol (men) or reduced levels of HDL cholesterol (men and women) or who smoked (women) had a higher prevalence of CAC. In contrast, no joint effects between plasma levels of Lp(a) and other cardiovascular risk factors on coronary calcium were found in blacks., Conclusions: No consistent independent relationship between plasma levels of Lp(a) or apolipoprotein(a) isoform size and coronary calcium was found in whites or blacks.

Background: The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart., Methods and Results: We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis., Conclusions: Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling.