Christine H J Won, Michelle Reid, Tamar Sofer
et al.
Abstract Study Objectives The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea–hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. Methods Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. Results The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%–10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. Conclusions There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.
Omar Dzaye, Philipp Berning, Zeina A Dardari
et al.
Abstract Aims This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown. Methods and results We included 6271 MESA participants, aged 45–84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7–14.7] for CAC = 0 and 35.8 (95% CI: 30.2–42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1–4.7)] and women [SHR: 2.2 (95% CI: 1.0–4.6)], but not significantly for sex-specific cancers across sexes. Conclusion CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.
Yaling Tang, Hetal Shah, Carlos Roberto Bueno Junior
et al.
OBJECTIVE The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in individuals with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS CAN was defined as heart rate variability indices below the fifth percentile of the normal distribution. Of 10,251 ACCORD participants, 71% (n = 7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models. RESULTS As compared with standard intervention, intensive glucose treatment reduced CAN risk by 16% (odds ratio [OR] 0.84, 95% CI 0.75–0.94, P = 0.003)—an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR 0.73, 95% CI 0.63–0.85, P < 0.0001) rather than those with CVD (OR 1.10, 95% CI 0.91–1.34, P = 0.34) (Pinteraction = 0.001). Intensive blood pressure (BP) intervention decreased CAN risk by 25% (OR 0.75, 95% CI 0.63–0.89, P = 0.001), especially in patients ≥65 years old (OR 0.66, 95% CI 0.49–0.88, P = 0.005) (Pinteraction = 0.05). Fenofibrate did not have a significant effect on CAN (OR 0.91, 95% CI 0.78–1.07, P = 0.26). CONCLUSIONS These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention.
Abstract All possible aza analogs of azulene, containing from one to three nitrogen atoms in the five-membered ring or from one to five nitrogen atoms in the seven-membered ring, have been theoretically considered to obtain information about their stabilities and aromaticities. Total electronic energy and nucleus independent chemical shift (NICS) data have been used to evaluate stability and aromaticity, respectively. The stabilities of the structures are strongly affected by the positions of the nitrogen atoms. Calculations of azaazulenes show that stability is decreased with close proximity of the nitrogen atoms. When nitrogen in the five-membered ring is adjacent to a ring junction, aromaticity of the cyclopentadienyl anion is reduced and that of the tropylium cation is increased. The number of nitrogen atoms affects the aromaticity of the system.
Abstract The efficient total synthesis of (±) solenopsin A ( 9 ) was achieved in a series of eight steps starting from readily available N -Bn- N -Boc alanine derivative 1 .