Plasma CD36 and Incident Diabetes:A Case-Cohort Study in Danish Men and Women

BACKGROUND: Membrane CD36 is a fatty acid transporter implicated in the pathogenesis of metabolic disease. We aimed to evaluate the association between plasma CD36 levels and diabetes risk and to examine if the association was independent of adiposity among Danish population.METHODS: We conducted a case-cohort study nested within the Danish Diet, Cancer and Health study among participants free of cardiovascular disease, diabetes and cancer and with blood samples and anthropometric measurements (height, weight, waist circumference, and body fat percentage) at baseline (1993 to 1997). CD36 levels were measured in 647 incident diabetes cases that occurred before December 2011 and a total of 3,515 case-cohort participants (236 cases overlap).RESULTS: Higher plasma CD36 levels were associated with higher diabetes risk after adjusting for age, sex and other lifestyle factors. The hazard ratio (HR) comparing high versus low tertile of plasma CD36 levels was 1.36 (95% confidence interval [CI], 1.00 to 1.86). However, the association lost its significance after further adjustment for different adiposity indices such as body mass index (HR, 1.23; 95% CI, 0.87 to 1.73), waist circumference (HR, 1.21; 95% CI, 0.88 to 1.68) or body fat percentage (HR, 1.20; 95% CI, 0.86 to 1.66). Moreover, raised plasma CD36 levels were moderately associated with diabetes risk among lean participants, but the association was not present among overweight/obese individuals.CONCLUSION: Higher plasma CD36 levels were associated with higher diabetes risk, but the association was not independent of adiposity. In this Danish population, the association of CD36 with diabetes risk could be either mediated or confounded by adiposity.</p

Optimization of respiratory-gated auricular vagus afferent nerve stimulation for the modulation of blood pressure in hypertension

BackgroundThe objective of this pilot study was to identify frequency-dependent effects of respiratory-gated auricular vagus afferent nerve stimulation (RAVANS) on the regulation of blood pressure and heart rate variability in hypertensive subjects and examine potential differential effects by sex/gender or race.MethodsTwenty hypertensive subjects (54.55 ± 6.23 years of age; 12 females and 8 males) were included in a within-person experimental design and underwent five stimulation sessions where they received RAVANS at different frequencies (i.e., 2 Hz, 10 Hz, 25 Hz, 100 Hz, or sham stimulation) in a randomized order. EKG and continuous blood pressure signals were collected during a 10-min baseline, 30-min stimulation, and 10-min post-stimulation periods. Generalized estimating equations (GEE) adjusted for baseline measures were used to evaluate frequency-dependent effects of RAVANS on heart rate, high frequency power, and blood pressure measures, including analyses stratified by sex and race.ResultsAdministration of RAVANS at 100 Hz had significant overall effects on the reduction of heart rate (β = −2.03, p = 0.002). It was also associated with a significant reduction of diastolic (β = −1.90, p = 0.01) and mean arterial blood pressure (β = −2.23, p = 0.002) in Black hypertensive participants and heart rate in female subjects (β = −2.83, p = 0.01) during the post-stimulation period when compared to sham.ConclusionRespiratory-gated auricular vagus afferent nerve stimulation exhibits frequency-dependent rapid effects on the modulation of heart rate and blood pressure in hypertensive patients that may further differ by race and sex. Our findings highlight the need for the development of optimized stimulation protocols that achieve the greatest effects on the modulation of physiological and clinical outcomes in this population

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.Methods The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (394 cases, 1,606 controls). Benign breast biopsy slides were reviewed by pathologists and CCL presence assessed. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between CCL and breast cancer risk. Results: Women with CCL (140 cases, 448 controls) had an increased risk of breast cancer compared with those without CCL (OR = 1.44, 95% CI: 1.14 to 1.83), although this was attenuated and became non-significant after adjustment for the histologic category of BBD (OR = 1.20, 95% CI: 0.94 to 1.54). CCL presence was associated with the greatest risk of breast cancer for those with nonproliferative BBD (OR = 1.36, 95% CI: 0.79 to 2.37) and the lowest risk for those with atypical hyperplasia (AH) (OR = 1.10, 95% CI: 0.65 to 1.87); however, this apparent heterogeneity in risk across BBD categories was not significant (P for interaction between CCL presence and BBD category = 0.77). Conclusions: These results provide evidence that CCL may be an important marker of breast cancer risk in women with BBD but suggest that CCL do not increase breast cancer risk independently of concurrent proliferative changes in the breast

Associations of HDL Subspecies Defined by ApoC3 with Non-Alcoholic Fatty Liver Disease: The Multi-Ethnic Study of Atherosclerosis.

Previously, we reported that inverse associations of high-density lipoprotein (HDL) with cardiovascular disease and diabetes were only observed for HDL that lacked the pro-inflammatory protein apolipoprotein C3 (apoC3). To provide further insight into the cardiometabolic properties of HDL subspecies defined by the presence or absence of apoC3, we aimed to examine these subspecies with liver fat content and non-alcoholic fatty liver disease (NAFLD). We investigated cross-sectional associations between ELISA-measured plasma levels of apoA1 in HDL that contained or lacked apoC3 and computed tomography-determined liver fat content and NAFLD (&lt;51 HU) at baseline (2000-2002) among 5007 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without heavy alcohol consumption (&gt;14 drinks/week in men and &gt;7 drinks/week in women). In multivariable-adjusted regression models, apoA1 in HDL that contained or lacked apoC3 was differentially associated with liver fat content (Pheterogeneity = 0.048). While apoA1 in HDL that lacked apoC3 was inversely associated with liver fat content (Ptrend &lt; 0.0001), apoA1 in HDL that contained apoC3 was not statistically significantly associated with liver fat content (Ptrend = 0.57). Higher apoA1 in HDL that lacked apoC3 was related to a lower prevalence of NAFLD (OR per SD: 0.80; 95% CI: 0.72, 0.89), whereas no association was found for apoA1 in HDL that contained apoC3 (OR per SD: 0.95; 95% CI: 0.85, 1.05; Pheterogeneity = 0.09). Higher apoA1 in HDL that lacked apoC3 was associated with less liver fat content and a lower prevalence of NAFLD. This finding extends the inverse association of HDL lacking apoC3 from cardiovascular disease to NAFLD. Lack of biopsy-proven hepatic steatosis and fibrosis data requires the replication of our study in further studies

High‐Density Lipoprotein Subspecies Defined by Apolipoprotein C‐III and Subclinical Atherosclerosis Measures: MESA (The Multi‐Ethnic Study of Atherosclerosis)

Background: Apolipoprotein C‐III (apoC‐III), a small proinflammatory protein present on 6% to 7% of high‐density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi‐ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC‐III–defined HDL subspecies and subclinical markers of atherosclerotic pathology. Methods and Results: We investigated cross‐sectional associations between apolipoprotein A‐I concentrations of apoC‐III–defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi‐Ethnic Study of Atherosclerosis) at baseline (2000–2002). HDL particles containing and lacking apoC‐III were divergently associated with coronary artery calcification in women (P‐heterogeneity=0.002) but not in men (P‐heterogeneity=0.31) and with carotid plaque score (P‐heterogeneity=0.02) and intima‐media thickness (P‐heterogeneity=0.06) in the overall study population. HDL lacking apoC‐III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73–0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84–1.00]; intima‐media thickness, overall: mean difference per SD=−14.0 µm [95% CI, −21.1 to −6.7 μm]), whereas HDL containing apoC‐III was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99–1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01–1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later. Conclusions: The presence of apoC‐III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC‐III in the pathophysiology of cardiovascular disease