Six-year changes in N-terminal pro-brain natriuretic peptide and changes in weight and risk of obesity

Objective: The aim of this study was to study the prospective association between N-terminal pro-brain natriuretic peptide (NT- proBNP) and changes in weight and obesity risk in a community-based population. Methods: Data from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT-proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT-proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight. Results: The prevalence of obesity increased from 28% to 35% in the 6-year follow-up period. Compared with individuals in the highest NT-proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08-1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow-up (odds ratio 1.35; 95% CI: 1.07-1.69). Changes in NT-proBNP were inversely associated with weight change. Conclusions: In this prospective study, lower levels of NT-proBNP were associated with higher risk of obesity, and changes in NT-proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity

Orthostatic Hypotension in Middle-Age and Risk of Falls

One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent

Incidence and pathophysiology of diabetes in south Asian adults living in India and Pakistan compared with US blacks and whites

Introduction: We compared diabetes incidence in South Asians aged ≥45 years in urban India (Chennai and Delhi) and Pakistan (Karachi), two low-income and middle-income countries undergoing rapid transition, with blacks and whites in the US, a high-income country.Research design and methods: We computed age-specific, sex-specific and body mass index (BMI)-specific diabetes incidence from the prospective Center for Cardiometabolic Risk Reduction in South Asia Study (n=3136) and the Atherosclerosis Risk in Communities Study (blacks, n=3059; whites, n=9924). We assessed factors associated with incident diabetes using Cox proportional hazards regression.Results: South Asians have lower BMI and waist circumference than blacks and whites (median BMI, kg/m2: 24.9 vs 28.2 vs 26.0; median waist circumference, cm 87.5 vs 96.0 vs 95.0). South Asians were less insulin resistant than blacks and whites (age-BMI-adjusted homeostatic model assessment of insulin resistance, µIU/mL/mmol/L: 2.30 vs 3.45 vs 2.59), and more insulin deficient than blacks but not whites (age-BMI-adjusted homeostasis model assessment of β-cell dysfunction, µIU/mL/mmol/L: 103.7 vs 140.6 vs 103.9). Age-standardized diabetes incidence (cases/1000 person-years (95% CI)) in South Asian men was similar to black men and 1.6 times higher (1.37 to 1.92) than white men (26.0 (22.2 to 29.8) vs 26.2 (22.7 to 29.7) vs 16.1 (14.8 to 17.4)). In South Asian women, incidence was slightly higher than black women and 3 times (2.61 to 3.66) the rate in white women (31.9 (27.5 to 36.2) vs 28.6 (25.7 to 31.6) vs 11.3 (10.2 to 12.3)). In normal weight (BMI \u3c25 kg/m2), diabetes incidence adjusted for age was 2.9 times higher (2.09 to 4.28) in South Asian men, and 5.3 times (3.64 to 7.54) in South Asian women than in white women.Conclusions: South Asian adults have lower BMI and are less insulin resistant than US blacks and whites, but have higher diabetes incidence than US whites, especially in subgroups without obesity. Factors other than insulin resistance (ie, insulin secretion) may play an important role in the natural history of diabetes in South Asians

Land Inequality and Rice Security in Northern Laos

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Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.</p

Severe Hypoglycemia, Cardiac Structure and Function, and Risk of Cardiovascular Events Among Older Adults With Diabetes.

OBJECTIVE: To assess the association of severe hypoglycemia measured at baseline with cardiovascular disease (CVD) among community-dwelling older individuals with diabetes, a group particularly susceptible to hypoglycemia. RESEARCH DESIGN AND METHODS: We included older adults with diabetes from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011-2013, baseline). Severe hypoglycemia at baseline was defined with use of first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls. We examined cross-sectional associations of severe hypoglycemia with echocardiographic indices of cardiac structure-function. We prospectively evaluated the risks of incident or recurrent CVD (coronary heart disease, stroke, or heart failure) and all-cause mortality, from baseline to 31 December 2018, using negative binomial and Cox regression models. RESULTS: Among 2,193 participants (mean [SD] age 76 [5] years, 57% female, 32% Blacks), 79 had a history of severe hypoglycemia at baseline. Severe hypoglycemia was associated with a lower left ventricular (LV) ejection fraction (adjusted β-coefficient -3.66% [95% CI -5.54, -1.78]), higher LV end diastolic volume (14.80 mL [95% CI 8.77, 20.84]), higher E-to-A ratio (0.11 [95% CI 0.03, 0.18]), and higher septal E/e (2.48 [95% CI 1.13, 3.82]). In adjusted models, severe hypoglycemia was associated with incident or recurrent CVD (incidence rate ratio 2.19 (95% CI 1.24, 3.88]) and all-cause mortality (hazard ratio 1.71 [95% CI 1.10, 2.67]) among those without prevalent CVD. CONCLUSIONS: Our findings suggest that a history of severe hypoglycemia is associated with alterations in cardiac function and is an important marker of future cardiovascular risk in older adults

Abstract P540: Sleep Duration, Rapid Eye Movement Sleep, and Subclinical Myocardial Damage

Abstract only Introduction: Sleep is strongly linked to clinical cardiovascular disease and was added in 2022 to the AHA’s Life’s Essential 8. Optimizing sleep duration and quality may reduce the risk of cardiovascular disease. Few studies have examined self-reported sleep duration and percent time in rapid eye movement (REM) sleep measured by single night in-home polysomnography with high sensitivity cardiac troponin T (hs-troponin T), a biomarker of subclinical cardiovascular disease. Methods: We conducted a cross-sectional study of adults without a history of cardiovascular disease who participated in both the Atherosclerosis Risk in Communities (ARIC) Study and the Sleep Heart Health Study (SHHS) in 1995-1998. We used linear regression with sleep duration and percentage time of REM sleep modeled as predictors with restricted cubic splines and examined associations with the outcome, hs-troponin T. We adjusted for age, sex, body mass index, waist-to-hip ratio, alcohol intake, smoking status, systolic blood pressure, hypertension medication use, diabetes, HDL- and LDL-cholesterol, and cholesterol-lowering medication use. Results: Among 1,587 participants (mean age 63, 54% female), the mean sleep duration was 7.3 hours, and mean % REM time was 20.7. Sleep duration was not associated with hs-troponin T ( Figure, Panel A ). However, percentage REM sleep was negatively associated with hs-troponin T, but with a threshold effect; there was a negative linear association of hs-troponin T with % REM sleep but only at values <15% ( Figure, Panel B ). Conclusion: While self-reported sleep duration was not associated with TnT levels, there was evidence that low % REM sleep, a specific neurophysiological sleep state, was associated with subclinical cardiovascular disease. These findings suggest that multiple sleep dimensions should be considered in efforts to optimize cardiovascular health

Incidence of diabetes in South Asian young adults compared to Pima Indians

Introduction South Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methods We used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).Results At baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI &lt;25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima IndiansConclusions In the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes

Orthostatic Hypotension in Middle-Age and Risk of Falls

BACKGROUND: One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent. METHODS: We conducted a prospective study of the association between baseline OH (1987–1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables. RESULTS: During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per −5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per −5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002). CONCLUSIONS: In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls