Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.

BACKGROUND: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. METHODS: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. RESULTS: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. CONCLUSIONS: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.

The co-existence of diabetes and subclinical atherosclerosis in rural central Appalachia: Do residential characteristics matter?

Aim Disparities exist in cardiovascular diseases (CVD) and diabetes in the United States (U.S.) with Central Appalachia having disproportionate burden. This study examined prevalence and correlates of CVD risk-factors among patients with diabetes/subclinical atherosclerosis in Central Appalachia. METHODS: During 2012-2016, 3000 patients from Central Appalachia were screened for subclinical atherosclerosis, using coronary artery calcium (CAC) scores; 419 participants had diabetes. Patients were categorized into four groups, with emphasis on those having subclinical atherosclerosis, CAC score ≥ 1. Descriptive statistics and multilevel multinomial logistic regression were conducted to identify CVD risk and spatial factors associated with co-existence of diabetes and subclinical atherosclerosis. RESULTS: Among participants, prevalence of CVD risk-factors ranged from 11.7% for current smokers to 69.2% for those with CVD family history. Average BMI was 29.8. Compared to patients with diabetes only, age [RR = 1.07; p ≤ 0.0001], being male [RR = 5.33; p ≤ 0.0001], having hypertension [RR = 2.37; p ≤ 0.05] and being a former smoker were associated with increased likelihood of having diabetes/subclinical atherosclerosis. At the zip-code level, unemployment rate [RR = 1.37; p ≤ 0.05] was significantly associated with having diabetes/subclinical atherosclerosis. CONCLUSION: Consistent with clinical guidelines, study results suggest the need to integrate CAC screening into primary care diabetes programs while addressing spatial issues that predispose patients to have diabetes/subclinical atherosclerosis.

Utility of routine non-gated CT chest in detection of subclinical atherosclerotic calcifications of coronary arteries in hospitalised HIV patients.

OBJECTIVES: To evaluate coronary artery calcification (CAC) on routine CT chest in hospitalised HIV patients and to assess individual risk factors. METHODS: Routine CT chests, May 2010-November 2015, of 143 hospitalised HIV-positive patients were reviewed for qualitative assessment of calcification in major coronary arteries by two radiologists. Presence, location and burden of calcification were evaluated on 3 mm axial images of CT chest. Cardiovascular risk factors and HIV lab parameters such as CD4 count, viral load and duration, and status of antiretroviral treatment were collected. Statistical analysis including multivariate logistic regression was performed. RESULTS: Forty-one patients (28.7%) showed CAC, left anterior descending (n = 38, 92.7%), circumflex (n = 18, 43.9%) and Right Coronary Artery (n = 13, 31.7%); mostly mild CAC burden and mostly proximal left coronary arteries with excellent interobserver and intraobserver agreements (K = 0.9, and 1). Age of CAC+ group (53.9 years) was significantly higher than CAC- group (43.4, p < 0.001, minimum age of CAC+, 27 years). No significant difference between two groups in sex, ethnicity and risk factors and HAART status. CAC+ group showed significantly longer HIV duration (12.3 years vs 8.6, p < 0.0344) and higher CD4 cell counts (mean = 355.9 vs 175.3, p = 0.0053) and significantly lower viral load (76 vs 414K, p = 0.02) than CAC- group. On multivariate logistic regression, age, HIV duration and CD4 were significantly associated with CAC+ (p-values < .05). CONCLUSIONS: One-third of hospitalised HIV patients showed subclinical CAC on CT chest. HIV duration and age of patients were independent risk factors for developing CAC. Higher CD4 cell count was strongly associated with CAC+. ADVANCES IN KNOWLEDGE: Routine CT chest with or without contrast performed for non-cardiac indications is helpful in identification of subclinical CAC in HIV patients and radiologists should be encouraged to report CAC.CAC is seen in younger age group in HIV, and awareness of this finding on routine CT chest would help guiding clinicians to assess risk stratification for primary prevention of ischemic heart disease in this population at an earlier stage when compared to normal population.Duration of HIV infection and age of patients were independent risk factors for developing CAC in our study and CD4 count was strongly associated with presence of CAC.

Predictive Value of Coronary Artery Calcium Score Categories for Coronary Events Versus Strokes: Impact of Sex and Race: MESA and DHS.

BACKGROUND: Coronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear. METHODS: White, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested. RESULTS: Among 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P<0.001). High CAC burden (score ≥100) was independently associated with ASCVD and CHD risk in all groups and with stroke risk in the overall cohort and Blacks. No sex- or race-based CAC interactions for ASCVD, CHD, and stroke events were observed. Adding CAC to a traditional risk factor model improved risk discrimination and reclassification for CHD but not for stroke events. CONCLUSIONS: In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

OBJECTIVE: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial. METHODS: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable. RESULTS: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20). CONCLUSION: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.

The relationship between endothelial function and aortic valve calcification: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population. METHODS: A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65 ±â€¯0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression. RESULTS: The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all p < 0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (p < 0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)]. CONCLUSIONS: Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors.

Coronary artery calcium testing: A call for universal coverage.

Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort.

OBJECTIVES: We sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM). BACKGROUND: CAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM. METHODS: We evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1-99, 100-300, and ≫300. We evaluated the association between CAC and all-cause mortality and CVD mortality. RESULTS: Overall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ±â€¯3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ≫ 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ≪1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1-99, 100-299 and ≫300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ≪ 0.001) and 5.75(95% CI 2.30, 14.37, P ≪ 0.001) in females with DM respectively; in males with DM HR associated with CAC 1-99, 100-299 and ≫300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively. CONCLUSION: Presence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.

Effect of patient visualization of coronary calcium by electron beam computed tomography on changes in beneficial lifestyle behaviors.

Despite convincing data demonstrating the benefits of aspirin (ASA), exercise, and dietary changes for both primary and secondary prevention of coronary heart disease, they remain underused. In this study, we assess whether higher coronary artery calcium (CAC) scores determined by electron beam computed tomography (EBCT) are associated with beneficial lifestyle behaviors in asymptomatic individuals. A total of 980 asymptomatic patients referred for EBCT risk assessment by their primary physician were sent a survey questioning them about health behaviors. We evaluated long-term ASA utilization, exercise, and dietary changes based on CAC using multivariable analysis. The study population consisted of 980 individuals (78% men, mean age 60 +/- 8 years) who were followed for a mean of 3 +/- 2 years after an initial EBCT scan. Overall, ASA initiation was lowest (29%) among those with CAC = 0, and gradually increased with higher CAC scores (1 to 99, 55%; 100 to 399, 61%; > or =400, 63%; p <0.001 for trend). Similarly, dietary changes and exercise were lowest (33% and 44%, respectively) among those with CAC = 0 and gradually increased with higher CAC scores (1 to 99, 40%; 100 to 399, 58%; > or =400, 56%; p <0.001 for trend for dietary changes; and 1 to 99, 62%; 100 to 399, 63%; > or =400, 67%; p <0.001 for trend for exercise). In multivariable analysis, greater baseline CAC was strongly associated with initiation of ASA therapy, dietary changes, and increased exercise. In conclusion, in addition to risk stratification of asymptomatic individuals, determination of CAC may also improve utilization of ASA therapy and behavioral modification.

A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study.

BACKGROUND: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients. STUDY DESIGN: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. SETTING & PARTICIPANTS: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography. INTERVENTIONS: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups. OUTCOMES & MEASUREMENTS: The primary end point was change in CAC score assessed by means of electron-beam computed tomography. RESULTS: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161). LIMITATIONS: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high. CONCLUSIONS: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

The Correlation of Dyslipidemia with the Extent of Coronary Artery Disease in the Multiethnic Study of Atherosclerosis.

BACKGROUND: The extent of coronary artery calcium (CAC) improves cardiovascular disease (CVD) risk prediction. The association between common dyslipidemias (combined hyperlipidemia, simple hypercholesterolemia, metabolic Syndrome (MetS), isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipidemia and the risk of multivessel CAC is underinvestigated. OBJECTIVES: To determine whether there is an association between common dyslipidemias compared with normolipidemia, and the extent of coronary artery involvement among MESA participants who were free of clinical cardiovascular disease at baseline. METHODS: In a cross-sectional analysis, 4,917 MESA participants were classified into six groups defined by specific LDL-c, HDL-c, or triglyceride cutoff points. Multivessel CAC was defined as involvement of at least 2 coronary arteries. Multivariate Poisson regression analysis evaluated the association of each group with multivessel CAC after adjusting for CVD risk factors. RESULTS: Unadjusted analysis showed that all groups except hypertriglyceridemia had statistically significant prevalence ratios of having multivessel CAC as compared to the normolipidemia group. The same groups maintained statistical significance prevalence ratios with multivariate analysis adjusting for other risk factors including Agatston CAC score [combined hyperlipidemia 1.41 (1.06-1.87), hypercholesterolemia 1.55 (1.26-1.92), MetS 1.28 (1.09-1.51), and low HDL-c 1.20 (1.02-1.40)]. CONCLUSION: Combined hyperlipidemia, simple hypercholesterolemia, MetS, and low HDL-c were associated with multivessel coronary artery disease independent of CVD risk factors and CAC score. These findings may lay the groundwork for further analysis of the underlying mechanisms in the observed relationship, as well as for the development of clinical strategies for primary prevention.

Association of Triglyceride-Related Genetic Variants With Mitral Annular Calcification.

BACKGROUND: Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown. OBJECTIVES: The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. METHODS: The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants. RESULTS: MAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio [OR] per triglyceride GRS unit: 1.73; 95% confidence interval [CI]: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy. CONCLUSIONS: Genetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.

Noninvasive FFR derived from coronary CT angiography in the management of coronary artery disease: technology and clinical update.

After a decade of clinical use of coronary computed tomographic angiography (CCTA) to evaluate the anatomic severity of coronary artery disease, new methods of deriving functional information from CCTA have been developed. These methods utilize the anatomic information provided by CCTA in conjunction with computational fluid dynamics to calculate fractional flow reserve (FFR) values from CCTA image data sets. Computed tomography-derived FFR (CT-FFR) enables the identification of lesion-specific drop noninvasively. A three-dimensional CT-FFR modeling technique, which provides FFR values throughout the coronary tree (HeartFlow FFRCT analysis), has been validated against measured FFR and is now approved by the US Food and Drug Administration for clinical use. This technique requires off-site supercomputer analysis. More recently, a one-dimensional computational analysis technique (Siemens cFFR), which can be performed on on-site workstations, has been developed and is currently under investigation. This article reviews CT-FFR technology and clinical evidence for its use in stable patients with suspected coronary artery disease.

Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: N-terminal pro B-type natriuretic peptide (NT-proBNP) is inversely associated with diabetes mellitus, obesity and metabolic syndrome. We aim to characterize the association between NT-proBNP and nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with metabolic syndrome. METHODS: 4529 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) free of cardiovascular disease, without self-reported liver disease and not diabetic at their baseline visit in 2000-2002 were included in this analysis. NAFLD was defined by a liver attenuation <40 HU. Relative prevalence (RP) for NAFLD was assessed adjusted for age, race, and sex, percentage of dietary calories derived from fat, total intentional exercise, alcoholic drinks per week, and interleukin-6 by quintiles of NT-proBNP. Adjusted linear spline model was used to characterize a non-linear association between NT-proBNP and liver fat. The inflection point (IP) was the NT-proBNP concentration where there was a change in slope in the association between liver attenuation and NT-proBNP. RESULTS: RP for NAFLD decreased by 30% from the lowest to the highest quintile of NT-proBNP, p=0.01. We observed an inverse linear association between NT-proBNP and liver fat, which plateaued (IP) at an NT-proBNP concentration of 45pg/mL. Linear regression coefficient (SE) per unit of NT-proBNP less than and greater than or equal to IP was of 0.05 (0.02), p=0.001 and 0.0006 (0.0008), p=0.5, respectively; differences between slopes, p<0.0001. CONCLUSIONS: In this cross-sectional study of a community based multiethnic sample of non-diabetic adults, low levels of NT-proBNP are associated with greater prevalence of NAFLD.

Variation in the percent of emphysema-like lung in a healthy, nonsmoking multiethnic sample. The MESA lung study.

RATIONALE: Computed tomography (CT)-based lung density is used to quantitate the percentage of emphysema-like lung (hereafter referred to as percent emphysema), but information on its distribution among healthy nonsmokers is limited. OBJECTIVES: We evaluated percent emphysema and total lung volume on CT scans of healthy never-smokers in a multiethnic, population-based study. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study investigators acquired full-lung CT scans of 3,137 participants (ages 54-93 yr) between 2010-12. The CT scans were taken at full inspiration following the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) protocol. "Healthy never-smokers" were defined as participants without a history of tobacco smoking or respiratory symptoms and disease. "Percent emphysema" was defined as the percentage of lung voxels below -950 Hounsfield units. "Total lung volume" was defined by the volume of lung voxels. MEASUREMENTS AND MAIN RESULTS: Among 854 healthy never-smokers, the median percent emphysema visualized on full-lung scans was 1.1% (interquartile range, 0.5-2.5%). The percent emphysema values were 1.2 percentage points higher among men compared with women and 0.7, 1.2, and 1.2 percentage points lower among African Americans, Hispanics, and Asians compared with whites, respectively (P < 0.001). Percent emphysema was positively related to age and height and inversely related to body mass index. The findings were similar for total lung volume on CT scans and for percent emphysema defined at -910 Hounsfield units and measured on cardiac scans. Reference equations to account for these differences are presented for never, former and current smokers. CONCLUSIONS: Similar to lung function, percent emphysema varies substantially by demographic factors and body size among healthy never-smokers. The presented reference equations will assist in defining abnormal values for percent emphysema and total lung volume on CT scans, although validation is pending.

Influence of estrogen therapy on calcium, phosphorus, and other regulatory hormones in postmenopausal women: the MESA study.

BACKGROUND: Estrogen therapy (ET) is associated with lower serum calcium and phosphorus concentrations and is known to increase bone mineral density (BMD). Other biomarkers of mineral metabolism may help understand the biological basis of these actions. METHODS: We studied 2767 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, 862 (31%) of whom were using ET. We measured serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D, 24,25-dihydoxyvitamin D, and fibroblast growth factor-23 and urinary fractional excretion of calcium (FEca) and phosphorus (FEphos). We examined the associations of ET with each biomarker. In addition, we tested whether the adjustment for biomarkers attenuated the association of ET with lumbar BMD measured by abdominal computed tomography in a subset of 810 women. RESULTS: In adjusted models, women who used ET were younger in age [62 (SD 8) vs 66 (9) y, P < .001], had lower mean serum calcium [-13 mg/dL (95% confidence interval [CI] -0.17, -0.10), P < .001] and lower FEca [-0.15% (95% CI -0.21, -0.09), P < .001]. Mean serum phosphorus was lower [-0.19 mg/dL (95% CI -0.23, -0.15), P < .001] and FEphos [0.56% (95% CI 0.16, 0.96), P = .007] was higher in women on ET. Mean 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were higher [1.52 ng/dL (95% CI 0.57, 2.47), P = .002, and 0.26 ng/mL (95% CI 0.03, 0.48), P = .03, respectively] in women who used ET. Mean PTH and fibroblast growth factor-23 did not differ significantly by the use of ET. ET use was strongly associated with higher lumbar BMD [12.75 mg/cm³ (95% CI 7.77-17.73), P < .001]; however, mineral metabolism measures did not meaningfully alter this association. CONCLUSIONS: In a multiethnic cohort of postmenopausal women, ET use was associated with lower serum calcium, lower FEca, lower serum phosphorus, and higher FEphos, suggesting these associations are attributable to increased calcium intake into bone and increased urinary phosphorus excretion. ET use was also associated with greater concentrations of vitamin D metabolites. ET-associated differences in these mineral metabolism measures did not meaningfully attenuate the strong association between ET use and lumbar BMD.

Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS).

OBJECTIVE: To determine whether self-reported menopausal symptoms are associated with measures of subclinical atherosclerosis. DESIGN: Cross-sectional analysis. SETTING: Multicenter, randomized controlled trial. PATIENT(S): Recently menopausal women (n = 868) screened for the Kronos Early Estrogen Prevention Study (KEEPS). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Baseline menopausal symptoms (hot flashes, dyspareunia, vaginal dryness, night sweats, palpitations, mood swings, depression, insomnia, irritability), serum E2 levels, and measures of atherosclerosis were assessed. Atherosclerosis was quantified using coronary artery calcium (CAC) Agatston scores (n = 771) and carotid intima-media thickness (CIMT). Logistic regression model of menopausal symptoms and E2 was used to predict CAC. Linear regression model of menopausal symptoms and E2 was used to predict CIMT. Correlation between length of time in menopause with menopausal symptoms, E2, CAC, and CIMT were assessed. RESULT(S): In early menopausal women screened for KEEPS, neither E2 nor climacteric symptoms predicted the extent of subclinical atherosclerosis. Palpitations and depression approached significance as predictors of CAC. Other symptoms of insomnia, irritability, dyspareunia, hot flashes, mood swings, night sweats, and vaginal dryness were not associated with CAC. Women with significantly elevated CAC scores were excluded from further participation in KEEPS; in women meeting inclusion criteria, neither baseline menopausal symptoms nor E2 predicted CIMT. Years since menopause onset correlated with CIMT, dyspareunia, vaginal dryness, and E2. CONCLUSION(S): Self-reported symptoms in recently menopausal women are not strong predictors of subclinical atherosclerosis. Continued follow-up of this population will be performed to determine whether baseline or persistent symptoms in the early menopause are associated with progression of cardiovascular disease. CLINICAL TRIAL REGISTRATION NUMBER: NCT00154180.