Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease.

Importance: Sibling death is a highly traumatic event, but empirical evidence on the association of sibling death in childhood and early adulthood with subsequent risk of incident cardiovascular disease (CVD) remains limited. Objective: To evaluate the association between sibling death in the early decades of life and subsequent risk of incident early-onset CVD. Design, Setting, and Participants: This population-based cohort study included 2 098 659 individuals born in Denmark from 1978 to 2018. Follow-up started at age 1 year or the date of the first sibling's birth, whichever occurred later, and it ended at the first diagnosis of CVD, the date of death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 1, 2021, through January 10, 2022. Exposures: The death of a sibling. Main Outcomes and Measures: The outcome was early-onset CVD. Cox models were used to estimate hazard ratios (HRs) with 95% CIs. Results: This study included 2 098 659 individuals (1 076 669 [51.30%] male; median [IQR] age at death of sibling, 11.48 [4.68-21.32] years). During the median (IQR) follow-up of 17.52 (8.85-26.05) years, 1286 and 76 862 individuals in the bereaved and nonbereaved groups, respectively, were diagnosed with CVD. Sibling death in childhood and early adulthood was associated with a 17% increased risk of overall CVD (HR, 1.17; 95% CI, 1.10-1.23; cumulative incidence in bereaved individuals, 1.96% [1.61%-2.34%]; cumulative incidence in nonbereaved individuals at age 41 years, 1.35% [1.34%-1.37%]; cumulative incidence difference: 0.61% [95% CI, 0.24%-0.98%]). Increased risks were also observed for most type-specific CVDs, in particular for myocardial infarction (HR, 1.66; 95% CI, 1.12-2.46), ischemic heart disease (HR, 1.52; 95% CI, 1.22-1.90), and heart failure (HR, 1.50; 95% CI, 1.00-2.26). The association was observed whether the sibling died due to CVD (HR, 2.54; 95% CI, 2.04-3.17) or non-CVD (HR, 1.13; 95% CI, 1.06-1.19) causes. The increased risk of CVD was more pronounced for individuals who lost a twin or younger sibling (HR, 1.25; 95% CI, 1.15-1.36) than an elder sibling (HR, 1.11; 95% CI, 1.03-1.20). Conclusions and Relevance: In this cohort study of the Danish population, sibling death in childhood and early adulthood was associated with increased risks of overall and most type-specific early-onset CVDs, with the strength of associations varying by cause of death and age difference between sibling pairs. The findings highlight the need for extra attention and support to the bereaved siblings to reduce CVD risk later in life.

Age-Dependent Association Between Body Mass Index and All-Cause Mortality Among Patients with Hypertension: A Longitudinal Population-Based Cohort Study in China.

Purpose: The association between body mass index (BMI) and all-cause mortality may vary among hypertensive patients of different ages. This study aimed to investigate the age-dependent association between BMI and all-cause mortality among patients with hypertension. Patients and Methods: A total of 212,394 participants with hypertension aged 20-85 years from Minhang Hypertension Standardization Management System in Shanghai of China were included. Follow-up began at the time when individuals were first recorded and ended at death, loss to follow-up, or December 31, 2018, whichever came first. Additive Cox proportional hazards models with thin plate smoothing functions and conventional Cox proportional hazards models were adopted to examine the relationship between BMI, age, and mortality. The joint effect of BMI and age on mortality was assessed using a bivariate response model. Results: We found that the BMI-mortality relationship followed a U-shaped pattern, with a trough at 26-27 kg/m2. Compared with normal weight, underweight was associated with a 50% increased risk of premature mortality (hazard ratio 1.50, 95% confidence interval 1.43 to 1.57). Whereas among those aged 45-59 and 60-85 years, overweight was associated with 13% (0.87, 0.80 to 0.94) and 18% (0.82, 0.80 to 0.84) reduction in risk of death, respectively. Bivariate response model indicated a significant interaction between BMI and age (P < 0.05). Among younger and older patients, we found a descending trend for mortality risk, with BMI increasing at different age levels, whereas a reverse J-shaped relation pattern was observed among middle-aged patients. Conclusion: The impact of BMI on all-cause mortality in hypertensive patients varies with age, and moderate weight gain may benefit longevity in middle-aged and older patients.

Association of Self-Reported Nighttime Sleep Duration with Chronic Kidney Disease: China Health and Retirement Longitudinal Study.

INTRODUCTION: The cohort study aimed to assess the association of nighttime sleep duration and the change in nighttime sleep duration with chronic kidney disease (CKD) and whether the association between nighttime sleep duration and CKD differed by daytime napping. METHODS: This study included 11,677 individuals from the China Health and Retirement Longitudinal Study (CHARLS) and used data from the 2011 baseline survey and four follow-up waves. Nighttime sleep duration was divided into three groups: short (<7 h per night), optimal (7-9 h), and long nighttime sleep duration (>9 h). Daytime napping was divided into two groups: no nap and with a nap. We used Cox proportional hazards model to examine the effect of nighttime sleep duration at baseline and change in nighttime sleep duration on incident CKD and a joint effect of nighttime sleep duration and nap time on onset CKD. RESULTS: With a follow-up of 7 years, the incidence of CKD among those with short, optimal, and long nighttime sleep duration was 9.89, 6.75, and 9.05 per 1,000 person-years, respectively. Compared to individuals with optimal nighttime sleep duration, short nighttime sleepers had a 44% higher risk of onset CKD (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.21-1.72). Compared to participants with persistent optimal nighttime sleep duration, those with persistent short or long nighttime sleep duration had an increased risk of incident CKD (HR: 1.44, 95% CI: 1.15-1.80). We found a lower incidence of CKD in participants with short nighttime sleep duration and a nap (HR: 0.74, 95% CI: 0.60-0.93), compared to those with short nighttime sleep duration and no nap. CONCLUSION: Short nighttime sleep duration and persistent long or short nighttime sleep duration were associated with a higher risk of onset CKD. Keeping persistent optimal nighttime sleep duration may help reduce CKD risk later in life. Daytime napping may be protective against CKD incidence.

Association Between Maternal Fasting Plasma Glucose Value and Fetal Weight Among Singletons of Mothers with Gestational Diabetes Mellitus.

Purpose: Infants with macrosomia are more likely to be born to mothers with gestational diabetes mellitus (GDM). This study aimed to investigate the associations between maternal blood glucose levels and fetal weight, placental weight, and risk of macrosomia in mothers with GDM. Patients and Methods: This retrospective study included 3211 singletons of mothers with GDM at the Shanghai First Maternity and Infant Hospital between January 2017 and December 2019. All women underwent an oral glucose tolerance test (OGTT) during the 24-28 weeks gestation period. Data on fetal and placental parameters were collected at delivery. Multiple linear regression models were used to evaluate the associations of maternal blood glucose levels with fetal weight and placental weight, while multiple logistic regression model was used to estimate the association between maternal blood glucose levels and the risk of macrosomia. Results: The prevalence of GDM in our study was 7%. Fasting plasma glucose (FPG) was positively correlated with fetal weight (r2=0.0329, P<0.001), and macrosomia risk (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.93-3.04; P<0.001). After adjusting for gestational age, the result remained significant (OR, 2.67; 95% CI, 2.11-3.38; P<0.001). In contrast, there was no significant relationship between 1-h plasma glucose (1hPG) or 2-h plasma glucose (2hPG) and fetal weight (P=0.18, P=0.46). Additionally, 1hPG or 2hPG was not strongly associated with macrosomia risk (OR, 0.95; 95% CI, 0.85-1.05; P=0.32 vs OR, 0.94; 95% CI, 0.85-1.05; P=0.28). Maternal blood glucose levels did not affect placental weight. The associations were similar in women carrying male and female fetuses. Conclusion: Maternal fasting plasma glucose levels were strongly associated with increased birth weight and macrosomia risk. Our findings suggest that fasting plasma glucose may predict birth weight.

Indoor Solid Fuel Use and Non-Neoplastic Digestive System Diseases: A Population-Based Cohort Study Among Chinese Middle-Aged and Older Population.

Objectives: We tended to explore the association of indoor air pollution (IAP) and non-neoplastic digestive system diseases (NNDSD) among the Chinese middle-aged and older population. Methods: From 2011 to 2018, we included 7884 NNDSD-free adults from the China Health and Retirement Longitudinal Study (CHARLS). Physician-diagnosed NNDSD was obtained by self-reported information at baseline and updated across follow-up surveys. We investigated the associations between baseline exposure of solid fuel use for cooking and/or heating and NNDSD diagnosed during follow-up through Cox proportional hazard models. Furthermore, we examined the relationship between cooking fuel switching and NNDSD diagnosed during follow-up. Results: Solid fuel use for cooking and/or heating was positively associated with NNDSD after adjusting for potential confounders. The risk of NNDSD among subjects who always use solid fuel for cooking (adjusted hazard ratio [aHR]: 1.42; 95% confidence interval [CI]: 1.09, 1.84) was higher than those with always clean fuels. Moreover, we found a lower NNDSD risk among participants who switched from solid to clean cooking fuel (aHR: 0.65; 95% CI: 0.49, 0.87) than those with always solid fuels. Conclusion: Our present study shows that indoor solid fuel use is a dependent risk factor for NNDSD. Moreover, switching to clean fuel may contribute to the prevention of digestive system illnesses.

Predictive Value of Novel Inflammation-Based Biomarkers for Pulmonary Hypertension in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Recently, there has been an increasing interest in the potential clinical use of several inflammatory indexes, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-immune-inflammation index (SII). This study aimed at assessing whether these markers could be early indicators of pulmonary hypertension (PH) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 185 patients were enrolled in our retrospective study from January 2017 to January 2019. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the clinical significance of these biomarkers to predict PH in patients with AECOPD. According to the diagnostic criterion for PH by Doppler echocardiography, the patients were stratified into two groups. The study group consisted of 101 patients complicated with PH, and the control group had 84 patients. The NLR, PLR, and SII values of the PH group were significantly higher than those of the AECOPD one (p < 0.05). The blood biomarker levels were positively correlated with NT-proBNP levels, while they had no significant correlation with the estimated pulmonary arterial systolic pressure (PASP) other than PLR. NLR, PLR, and SII values were all associated with PH (p < 0.05) in the univariate analysis, but not in the multivariate analysis. The AUC of NLR used for predicting PH was 0.701 and was higher than PLR and SII. Using 4.659 as the cut-off value of NLR, the sensitivity was 81.2%, and the specificity was 59.5%. In conclusion, these simple markers may be useful in the prediction of PH in patients with AECOPD.

Catalytic asymmetric tandem Friedel-Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans.

The enantioselective tandem Friedel-Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by a diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee).