Background and objective

The goal of this work was to determine whether midlife cardiac structure and function and their 25-year change from early to middle adulthood are associated with lower midlife cognition.

Methods

We studied 2,653 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study (57% women, 46% Black). Echocardiograms were obtained at year 5, 25, and 30 visits (participant mean age 30, 50, and 55 years) to assess left ventricular (LV) mass (LVM), LV systolic function with LV ejection fraction (LVEF), and LV diastolic function with left atrial volume (LAV) and early peak mitral velocity (E)/early peak mitral annular velocity (e') ratio. LVM and LAV were indexed to body surface area (LVMi and LAVi). At year 30, 5 cognitive domains were measured: global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency. We investigated the association between midlife (year 30) and 25-year change in cardiac structure and function on midlife cognition using linear regressions.

Results

Over 25 years, LVMi and LAVi increased with mean change (SD) per year of 0.27 (0.28) g/m² and 0.42 (0.15) mL/m², while LVEF decreased by 0.11% (0.02%). After adjustment for demographics and education, 25-year increase (≥1 SD) in LVMi was associated with lower cognition on most tests (p ≤ 0.02); 25-year increase in LAVi was associated with lower global cognition (p = 0.04), but 25-year decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors led to similar results. In addition, unlike year 30 E/e' ratio and LVEF, higher year 30 LVMi and LAVi were significantly associated with worse cognition on most cognitive tests.

Discussion

Midlife cardiac structure and its change from early to middle adulthood are associated with lower midlife cognition even after accounting for confounders. Unlike systolic function, midlife LV diastolic function and its 25-year change were also linked to cognition. Our results provide information linking early to midlife cardiac structure and function to cognition.

Objective

Both coronary artery calcification (CAC) and the ankle brachial index (ABI) are measures of subclinical atherosclerotic disease. The influence of physical activity on the longitudinal change in these measures remains unclear. To assess this relation we examined the association between these measures and self-reported physical activity in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

At baseline, the MESA participants were free of clinically evident cardiovascular disease. We included all participants with an ABI between 0.90 and 1.40 (n = 5656). Predictor variables were based on self-reported measures with physical activity being assessed using the Typical Week Physical Activity Survey from which metabolic equivalent-minutes/week of activity were calculated. We focused on physical activity intensity, intentional exercise, sedentary behavior, and conditioning. Incident peripheral artery disease (PAD) was defined as the progression of ABI to values below 0.90 (given the baseline range of 0.90-1.40). Incident CAC was defined as a CAC score >0 Agatston units upon follow up with a baseline score of 0 Agatston units.

Results

Mean age of participants was 61 years, 53% were female, and mean body mass index was 28 kg/m(2). After adjusting for traditional cardiovascular risk factors and socioeconomic factors, intentional exercise was protective for incident peripheral artery disease (Relative Risk (RR) = 0.85, 95% Confidence Interval (CI): 0.74-0.98). After adjusting for traditional cardiovascular risk factors and socioeconomic factors, there was a significant association between vigorous PA and incident CAC (RR = 0.97, 95% CI: 0.94-1.00). There was also a significant association between sedentary behavior and increased amount of CAC among participants with CAC at baseline (Δlog (Agatston Units + 25) = 0.027, 95% CI 0.002, 0.052).

Conclusions

These data suggest that there is an association between physical activity/sedentary behavior and the progression of two different measures of subclinical atherosclerotic disease.

Heart failure (HF) is a leading cause of morbidity. Strategies for preventing HF are paramount. Prevalent extracoronary calcification is associated with HF risk but less is known about progression of mitral annular (MAC) and aortic valve calcification (AVC) and HF risk. Progression of valvular calcification (VC) [interval change of >0 units/yr] was assessed by 2 cardiac computed tomography scans over a median of 2.4 years. We used Cox regression to determine the risk of adjudicated HF and linear mixed effects models to determine 10-year change in left ventricular (LV) parameters measured by cardiac magnetic resonance imaging associated with VC progression. We studied 5,591 MESA participants free of baseline cardiovascular disease. Mean ± SD age was 62 ± 10 years; 53% women; 83% had no VC progression, 15% progressed at 1 site (AVC or MAC) and 3% at both sites. There were 251 incident HF over 15 years. After adjusting for cardiovascular risk factors, the hazard ratios (95% confidence interval) of HF associated with VC progression at 1 and 2 sites were 1.62 (1.21 to 2.17) and 1.88 (1.14 to 3.09), respectively, compared with no progression (p-for-trend <0.001). Hazard ratios were higher for HFpEF (2.52 [1.63 to 3.90] and 2.49 [1.19 to 5.25]) but nonsignificant for HFrEF. Both AVC (1.61 [1.19 to 2.19]) and MAC (1.50 [1.09 to 2.07]) progression were associated with HF. VC was associated with worsening of some LV parameters over 10 years. In conclusion, VC progression was associated with increased risk of HF and change in LV function. Interventions targeted at reducing VC progression may also impact HF risk, particularly HFpEF.

Background

Although left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts.

Methods

An atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts.

Results

The atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices.

Conclusions

We have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations.

Trial registration

ClinicalTrials.gov NCT00005487.

Background and aims

To balance competing cardiovascular benefits and metabolic risks of statins, markers of type 2 diabetes (T2D) susceptibility are needed. We sought to define a competing risk/benefit of statin therapy on T2D and cardiovascular disease (CVD) events using liver attenuation and coronary artery calcification (CAC).

Methods and results

3153 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or baseline statin therapy had CT imaging for CAC and hepatic attenuation (hepatic steatosis). Cox models and rates of CVD and T2D were calculated to assess the role of liver attenuation in T2D and the relative risks/benefits of statins on CVD and T2D. 216 T2D cases were diagnosed at median 9.1 years follow-up. High liver fat and statin therapy were associated with diabetes (HR 2.06 [95%CI 1.52-2.79, P < 0.0001] and 2.01 [95%CI 1.46-2.77, P < 0.0001], respectively), after multivariable adjustment. With low liver fat and CAC = 0, the number needed to treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the number needed to harm (NNH) with an incident case of T2D (NNH 68). Conversely, those with CAC >100 and low liver fat were more likely to benefit from statins for CVD reduction (NNT 29) relative to T2D risk (NNH 67). Among those with CAC >100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less than incremental risk increase for T2D (NNH 24).

Conclusions

Liver fat is associated with incident T2D and stratifies competing metabolic/CVD risks with statin therapy. Hepatic fat may inform T2D surveillance and lipid therapeutic strategies.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure.

Abstract Background Cardiovascular imaging studies generate a wealth of data which is typically used only for individual study endpoints. By pooling data from multiple sources, quantitative comparisons can be made of regional wall motion abnormalities between different cohorts, enabling reuse of valuable data. Atlas-based analysis provides precise quantification of shape and motion differences between disease groups and normal subjects. However, subtle shape differences may arise due to differences in imaging protocol between studies. Methods A mathematical model describing regional wall motion and shape was used to establish a coordinate system registered to the cardiac anatomy. The atlas was applied to data contributed to the Cardiac Atlas Project from two independent studies which used different imaging protocols: steady state free precession (SSFP) and gradient recalled echo (GRE) cardiovascular magnetic resonance (CMR). Shape bias due to imaging protocol was corrected using an atlas-based transformation which was generated from a set of 46 volunteers who were imaged with both protocols. Results Shape bias between GRE and SSFP was regionally variable, and was effectively removed using the atlas-based transformation. Global mass and volume bias was also corrected by this method. Regional shape differences between cohorts were more statistically significant after removing regional artifacts due to imaging protocol bias. Conclusions Bias arising from imaging protocol can be both global and regional in nature, and is effectively corrected using an atlas-based transformation, enabling direct comparison of regional wall motion abnormalities between cohorts acquired in separate studies.

Objective

Obesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.

Methods

We examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).

Results

Higher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.

Conclusions

Leptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation.

Objective

To measure association between hepatic fat and albuminuria (an early marker of renal injury) in individuals without diabetes or hypertension.

Methods

2,281 individuals in the Multi-Ethnic Study of Atherosclerosis without diabetes or hypertension, renal disease, or excess alcohol consumption underwent computed tomography (CT) for assessment of liver attenuation (marker of hepatic lipid content) and urinalysis (for albuminuria) at initial study visit, with assessment of incident and prevalent albuminuria by logistic regression in follow-up.

Results

After adjustment for age, gender, race, smoking, blood pressure, insulin resistance, and body mass index, individuals with less liver fat (higher liver CT attenuation) had a lower probability of having albuminuria at Exam 1 (OR per 10 unit increase in attenuation 0.77, 95 % CI 0.61-0.97, P = 0.02). At median 9.3 years follow-up, albuminuria was identified in 129 individuals were (5.8 %). In fully adjusted models (with age, smoking, body mass index, blood pressure, diabetes and hypertension as time-dependent covariates), lower liver attenuation (greater liver fat) was associated with higher risk of incident albuminuria (OR 0.79, 95 % CI 0.66-0.94, P = 0.008).

Conclusions

Hepatic attenuation is associated with prevalent and incident albuminuria, an early, potent risk factor for renal risk in a population not clearly at risk for future renal failure.