Abstract Ageing conveys the greatest risk for cardiovascular disease (CVD) development, which is the dominant cause of mortality in developed nations. High density lipoprotein (HDL) particles mediate reverse cholesterol transport, are anti-inflammatory and their function predicts CVD. We observed lower plasma cholesterol efflux capacity in geriatric vervet monkeys (p=0.03) when consuming either healthy or Western diets. Adult (n=16) and geriatric (n=19) monkeys were stratified into groups fed Western diet on ad libitum (Ad Lib) or early time restricted feeding (eTFR) schedules. eTRF supplied excess food only between 6am to 2pm. Housing, seasonality and fasting conditions for data and sample collections were equivalent. After 6 months, cholesterol efflux to HDL was greater in eTRF monkeys (p=0.01), with no age by group interaction. Efflux media and plasma was chromatographically separated to confirm labelled cholesterol, and enzymatically measured cholesterol, respectively, was affiliated with HDL particles. eTRF monkeys had higher total plasma cholesterol levels (p=0.03) which was due to greater cholesterol amounts associated with only HDL, and resulted in HDL particles that were larger. eTRF resulted in robustly better HDL function such that measures from geriatric individuals were comparable to younger adults. Additionally, no differences in adiposity was observed in eTRF monkeys. Few interventions are known to raise HDL levels, and more importantly, are confirmed to improve HDL function. Our study is to date the largest, longest, controlled eTRF evaluation in primates and we show that positive biological effects are observable in HDL isolated from both adult and geriatric individuals independently of weight change.
The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non–ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.