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BackgroundApolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels.AimsTo investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis.MethodsA prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively.ResultsIn 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91–2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07–1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07–1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67–1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality.ConclusionBoth very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.

The concept of thermal therapy toward the treatment of brain tumors has gained traction in recent years. Traditionally, thermal therapy has been subdivided into hyperthermia, with mild elevation of temperature in treated tissue above the physiologic baseline; and thermal ablation, where even higher temperatures are achieved. The recent surge in interest has been driven by the use of novel thermal ablation technologies, including laser interstitial thermal therapy (LITT), that are implemented in brain tumor treatment. Here, we review previous scientific literature on the biologic effects of thermal therapy on brain tumors, with an emphasis on glioblastoma (GBM), an aggressive brain malignancy. In addition, we present in vitro evidence from our laboratory that even moderate elevations in temperature achieved in the penumbra around laser-ablated coagulum may also produce GBM cell death. While much remains to be elucidated in terms of the biology of thermal therapy, we propose that it is a welcome addition to the neuro-oncology armamentarium, in particular with regard to GBM, which is generally resistant to current chemoradiotherapeutic regimens.

Supplemental Digital Content is available in the text., Objective: The underlying pathobiology of the paradoxical relationship between obesity and adverse outcomes in coronary artery disease (CAD) is unclear. Our objective was to determine the association between obesity and circulating progenitor cell (CPC) counts—a measure of intrinsic regenerative capacity—in asymptomatic individuals and patients with CAD and its impact on the obesity paradox. Approach and Results: CPCs were enumerated by flow cytometry as CD45med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 years of age; 28% obese) and 1277 patients with CAD (66 years of age; 39% obese). The association between obesity and CPCs was analyzed using linear regression models. The association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-year follow-up in patients with CAD was studied using Cox models. Obesity was independently associated with 16% to 34% higher CPC counts (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated by systemic inflammation, insulin resistance, or secretion but partly attenuated by cardiorespiratory fitness and body composition. In patients with CAD, obesity was associated with 8% to 12% higher CPC counts and 30% lower risk of adverse outcomes. Compared with nonobese patients, only obese patients with high CPC counts (CD34+ cells ≥median, 1806 cells/mL) were at a lower risk (hazard ratio, 0.52 [95% CI, 0.31–0.88]), whereas those with low counts (

Background Women have higher circulating levels of soluble urokinase‐type plasminogen activator receptor (suPAR), and elevated suPAR is associated with cardiovascular risk. The independent association of sex with suPAR and the impact of sex on its association with cardiovascular risk are unknown. Methods and Results Plasma suPAR was measured using ELISA in 2 cohorts of 666 asymptomatic individuals (49 years, 65% women) and 4184 patients with coronary artery disease (63 years, 37% women). Independent association of sex with suPAR was studied using linear regression models adjusted for demographics, risk factors, and visceral adiposity in asymptomatic participants. Impact of sex on association of suPAR with all‐cause mortality was studied in patients with coronary artery disease using multivariable‐adjusted Cox models. Sex‐specific suPAR cutoffs for predicting all‐cause mortality were calculated. Asymptomatic women had 10% higher suPAR compared with men after adjusting for confounders, and visceral adiposity partly accounted for this association. Over a median follow‐up of 5.2 years, 795 deaths were recorded in patients with coronary artery disease. Log 2 ‐transformed suPAR was independently associated with mortality (hazard ratio per 1‐SD 1.72, 95% CI 1.60–1.85) and an interaction with sex was noted ( P =0.005). Association of suPAR with mortality was slightly weaker in women (hazard ratio 1.61, 95% CI 1.41–1.83) compared with men (hazard ratio 1.83, 95% CI 1.67–2.00). However, using sex‐specific suPAR cut‐offs (4392 pg/mL for women and 3187 pg/mL for men), a similar mortality incidence was observed for both sexes (38.5% and 35.5%, respectively, P =0.3). Conclusions Women have 10% higher plasma suPAR levels compared with men. Elevated sex‐specific plasma suPAR levels are equally predictive of risk of adverse events in both sexes.