Mitral annular calcification as a predictor of stroke in the multiethnic study of atherosclerosis.

BACKGROUND: Mitral annular calcification (MAC) is associated with an increased risk for cardiovascular morbidity and mortality. This study provides recent data on the association between cardiac computed tomography (CT) derived MAC and 15 years of stroke risk in a racially diverse cohort. METHODS: All multiethnic studies of atherosclerosis participants ( n  = 6814) who completed a cardiac CT at baseline were included in this analysis. MAC score was calculated from cardiac CT using the Agatston and volume score methods. Multivariable Cox proportional hazard regression models were used to compute hazard ratios for the association between MAC and stroke after adjusting for traditional cardiovascular risk factors, inflammatory markers, coronary artery calcium score, atrial fibrillation, and left atrial size. RESULTS: Overall, 9% of participants (644/6814) had MAC at baseline. Over a surveillance period of 15 years, 304 strokes occurred, and 79% were ischemic strokes. After adjusting for age, sex, race/ethnicity, SBP, diabetes, smoking, fibrinogen, IL-6, high-sensitivity C-reactive protein, and coronary artery calcium score, baseline MAC was associated with increased risk for all strokes [hazard ratio 1.68; 95% confidence interval (CI) 1.22-2.30: P  = 0.0013]. When atrial fibrillation/flutter and left atrial size were included in the final multivariable model, MAC remained a predictor of all strokes (hazard ratio 1.93; 95% CI 1.22-3.05: P  < 0.0051) and ischemic stroke (hazard ratio 2.03; 95% CI 1.24-3.31: P  < 0.0046). CONCLUSION: MAC is an independent predictor of long-term stroke risk in a racially diverse population beyond conventional cardiovascular risk factors and atrial fibrillation.

Ten-Year Changes in Television Viewing and Physical Activity Are Associated With Concurrent 10-Year Change in Pericardial Adiposity: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Longitudinal association of television (TV) viewing and moderate- to vigorous-intensity physical activity (MVPA) with pericardial adipose tissue (PAT) is unclear. METHODS: We studied Coronary Artery Risk Development in Young Adults Study participants transitioning from early to middle age at Coronary Artery Risk Development in Young Adults (CARDIA) exam years 15 (2000-2001; N = 1975, mean age = 40.4, 55.4% women, 45.3% Black) and 25 (2010-2011). TV viewing (in hours per day) and MVPA (in exercise units) were measured using a self-report questionnaire. PAT volume (in milliliters) was measured using computed tomography. Multivariable linear regression was used to examine the associations of tertiles of 10-year change (years 25-15) in TV viewing and MVPA with a concurrent change in PAT with adjustments for covariates. RESULTS: Participants in the highest tertile of 10-year increase in TV viewing had a greater increase in PAT (ß = 2.96 mL, P < .01). Participants in both middle (ß = -3.93 mL, P < .01) and highest (ß = -6.22 mL, P < .01) tertiles of 10-year changes in MVPA had smaller mean increases in PAT over 10 years when compared with the lowest tertile in fully adjusted models. CONCLUSIONS: Reducing or maintaining early-midlife levels of TV viewing and increasing MVPA may be associated with less PAT accumulation with age.

Relationship of Subcutaneous Adipose Tissue Inflammation-Related Gene Expression With Ectopic Lipid Deposition in Persons With HIV.

OBJECTIVE: Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART. DESIGN AND METHODS: A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis. RESULTS: Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, including CCL2, CCL22, CCL13, CCR1, CD86, CD163, IL-6, IL-10, MRC1, and TREM2, which were associated with an increased lipid deposition in multiple ectopic depots. CONCLUSION: Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.

Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women.

BACKGROUND & AIMS: Lactation lowers blood glucose and triglycerides, and increases insulin sensitivity. We hypothesized that a longer duration of lactation would be associated with lower prevalence of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease in the United States. METHODS: Participants from the Coronary Artery Risk Development in Young Adults cohort study who delivered ≥ 1 child post-baseline (Y0: 1985-1986), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n = 844). The duration of lactation was summed for all post-baseline births, and NAFLD at Y25 was assessed by central review of CT images and defined by liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of hepatic steatosis. Unadjusted and multivariable logistic regression analyses were performed using an a priori set of confounding variables; age, race, education, and baseline body mass index. RESULTS: Of 844 women who delivered after baseline (48% black, 52% white, mean age 49 years at Y25 exam), 32% reported lactation duration of 0 to 1 month, 25% reported >1 to 6 months, 43% reported more than 6 months, while 54 (6%) had NAFLD. Longer lactation duration was inversely associated with NAFLD in unadjusted logistic regression. For women who reported >6 months lactation compared to those reporting 0-1 month, the odds ratio for NAFLD was 0.48 (95% CI 0.25-0.94; p = 0.03) and the association remained after adjustment for confounders (adjusted odds ratio 0.46; 95% CI 0.22-0.97; p = 0.04). CONCLUSIONS: A longer duration of lactation, particularly greater than 6 months, is associated with lower odds of NAFLD in mid-life and may represent a modifiable risk factor for NAFLD. LAY SUMMARY: A longer duration of breastfeeding has been associated with multiple potential health benefits for the mother including reduction in heart disease, diabetes and certain cancers. In this study we found that breastfeeding for longer than 6 months was associated with a lower risk of non-alcoholic fatty liver disease in mid-life.

Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

OBJECTIVE: The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. SUMMARY OF BACKGROUND DATA: Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). METHODS: We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m) were identified and assigned weighted points to calculate risk scores. RESULTS: A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. CONCLUSIONS: Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.