Search

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One‐sample Mendelian randomization (MR) and summary data‐based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one‐sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65–0.90; p = 0.001) and CCB use (0.83; 0.72–0.95; p = 0.007), equivalent to a 10‐mm Hg reduction in systolic BP, was significantly associated with lower risk of pre‐frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39–1.33; p = 0.296) or thiazides variants (0.74; 0.53–1.03; p = 0.072) on pre‐frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta −0.02, p = 2.87 × 10−4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty. [ABSTRACT FROM AUTHOR]

Little is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. We included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7–8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. During a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0–1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). Measurement error was unavoidable for self-reported data on sleep behaviors. Our analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern. • Adherence to a healthy sleep pattern was associated with a reduced risk of chronic liver diseases. • Healthy sleep pattern and genetic predisposition may synergistically influence the risks of chronic liver diseases. • Our findings underscore the importance of extensive intervention targeting sleep behaviors should be undertaken to reduce the risk of chronic liver diseases. [ABSTRACT FROM AUTHOR]

Aims: We aimed to examine the longitudinal associations of birth weight with plasma metabolites in adulthood, and further quantify the proportions of the links between birth weight and incident adult type 2 diabetes (T2D) that were mediated by plasma metabolites. Materials and Methods: A total of 62,033 participants with complete nuclear magnetic resonance metabolomics and birth weight data from the UK Biobank were included in this study. Linear regression was used to assess the associations between birth weight and metabolites. Cox regression was used to estimate hazard ratios for T2D associated with metabolites. We further performed mediation analyses to estimate the extent to which metabolites might mediate the association between birth weight and T2D risk. Results: Low birth weight was associated with the adverse metabolic responses across multiple metabolic pathways, including lipoprotein subclasses, amino acids, fatty acids (FA), and inflammation. Metabolites associated with higher birth weight tended to be associated with a lower risk of T2D (Pearson correlation coefficient: −0.85). A total of 62 metabolites showed statistically significant mediation effects in the protective association of higher birth weight and T2D risk, including large‐sized very low‐density lipoprotein particles and triglyceride concentrations as well as saturated, and monounsaturated FA and glycoprotein acetyls. Conclusions: We identified a range of metabolites that reflect the adult metabolic response to birth weight, some of which might lie on the pathway between birth weight and adult T2D risk. [ABSTRACT FROM AUTHOR]

The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity. Dysmetabolism of triglyceride-rich lipoproteins is considered a shared risk factor for cardiometabolic diseases, but their associations with cardiometabolic multimorbidity have not been fully understood. Here, the authors show that elevated levels of remnant cholesterol and triglycerides were observationally and genetically associated with a higher risk of cardiometabolic multimorbidity. [ABSTRACT FROM AUTHOR]

Background To establish a polysocial risk score (PsRS) incorporating various social factors for capturing the dementia risk and investigate the benefits of favorable social conditions across different genetic backgrounds. Methods This prospective cohort study comprised 345 439 participants initially free of dementia from the UK Biobank. A total of 10 social factors were summed to create a PsRS. A polygenic risk score (PRS) was constructed based on genome-wide significant variants. Results During a median follow-up of 12.5 years, we documented 4 595 incident all-cause dementia events including 2 067 Alzheimer's disease (AD) events and 1 028 vascular dementia (VD) events. Each additional PsRS was associated with a 19% increased risk of all-cause dementia (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.17 to 1.21), a 13% increased risk of AD (1.13; 1.10 to 1.16), and a 24% increased risk of VD (1.24; 1.19 to 1.29). 29% (24% to 33%) of dementia cases, 22% (14% to 29%) of AD cases, and 39% (28% to 48%) of VD cases were associated with a disadvantageous social environment. In addition, among participants at a high genetic risk, the low social risk was linked to a lower incidence rate of all-cause dementia, AD, and VD compared to those who had a high social risk, with reductions of 67.8%, 64.5%, and 84.2%, respectively. Conclusions The PsRS could be effectively used in discriminating individuals at high risk of dementia. Around a quarter of dementia events could have a connection with a disadvantageous social environment, especially for those genetically susceptible to dementia. [ABSTRACT FROM AUTHOR]

The healthy aging index (HAI) has been recently developed as a surrogate measure of biological age. However, to what extent the HAI is associated with all-cause and cause-specific mortality and whether this association differs in younger and older adults remains unknown. We aimed to quantify the association between the HAI and mortality in a population of UK adults. In the prospective cohort study, data are obtained from the UK Biobank. Five HAI components (systolic blood pressure, reaction time, cystatin C, serum glucose, forced vital capacity) were scored 0 (healthiest), 1, and 2 (unhealthiest) according to sex-specific tertiles or clinically relevant cut-points and summed to construct the HAI (range 0–10). Cox proportional hazard regression models were used to estimate the associations of the HAI with the risk of all-cause and cause-specific mortality. 387,794 middle-aged and older participants were followed up for a median of 8.9 years (IQR 8.3–9.5). A total of 14,112 all-cause deaths were documented. After adjustments, each 1-point increase in the HAI was related to a higher risk of all-cause mortality (hazards ratio [HR], 1.17; 95%CI, 1.15–1.18). Such association was stronger among adults younger than 60 years (1.19, 1.17–1.21) than that among those 60 years and older (1.15, 1.14–1.17) (P interaction < 0.001). For each unit increment of the HAI, the multivariate-adjusted HRs for risk of death were 1.28 (1.25–1.31) for cardiovascular diseases, 1.09 (1.07–1.10) for cancer, 1.36 (1.29–1.44) for digestive disease, 1.42 (1.35–1.48) for respiratory disease, 1.42 (1.33–1.51) for infectious diseases, and 1.15 (1.09–1.21) for neurodegenerative disease, respectively. Our findings indicate that the HAI is positively associated with all-cause and cause-specific mortality independent of chronological age. Our results further underscore the importance of effective early-life interventions to slow aging and prevent premature death. [ABSTRACT FROM AUTHOR]

Background Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies. Methods We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings. Results Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes. Conclusions This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories. [ABSTRACT FROM AUTHOR]

Introduction: Time spent on screen-based sedentary activities is significantly associated with dementia risk, however, whether the associations vary by family history (FHx) of dementia is currently unknown. We aimed to examine independent associations of two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) with dementia and assess the modifying effect of FHx. Methods: We included 415,048 individuals free of dementia from the UK Biobank. Associations of TV viewing, computer use, and FHx with dementia risk were determined using Cox regression models. We estimated both multiplicative- and additive-scale interactions between TV viewing and computer use and FHx. Results: During a median follow-up of 12.6 years, 5,549 participants developed dementia. After adjusting for potential confounding factors, we observed that moderate (2–3 h/day; hazard ratio [HR] 1.13, 95% confidence interval 0.03–1.23) and high (>3 h/day; 1.33, 1.21–1.46) TV viewing was associated with a higher dementia risk, compared with low (0–1 h/day) TV viewing. Using restricted cubic spline models, the relationship of TV viewing with dementia was nonlinear (relative to 0 h/day; p for nonlinear = 0.005). We found that >3 h/day of TV viewing was associated with a 42% (1.42, 1.18–1.71) higher dementia risk in participants with FHx while a 30% (1.30, 1.17–1.45) in those without FHx. For computer use, both low (0 h/day; 1.41, 1.33–1.50) and high (>2 h/day; 1.17, 1.05–1.29) computer use were associated with elevated dementia risk, compared with moderate (1–2 h/day) computer use. We observed a J-shaped relationship with dementia (relative to 2 h/day; p for nonlinear <0.001). Compared with 1–2 h/day of computer use, the HRs of dementia were 1.46 (1.29–1.65) and 1.10 (0.90–1.36) for 0 h/day and >2 h/day of computer use in participants with FHx, respectively, while the corresponding HRs were 1.40 (1.30–1.50) and 1.19 (1.06–1.33) in those without FHx. We observed a positive additive interaction (RERI 0.29, 0.06–0.53) between computer use and FHx, while little evidence of interaction between TV viewing and FHx. Conclusions: The time spent on TV viewing and computer use were independent risk factors for dementia, and the adverse effects of computer use and FHx were additive. Our findings point to new behavioral targets for intervention on preventing an early onset of dementia, especially for those with FHx. [ABSTRACT FROM AUTHOR]

Researchers have identified an association between lifestyle factors and colorectal cancer (CRC) risk. This study examined the relationship between sleep patterns and CRC events. 392,252 individuals were sampled from the UK Biobank. Chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness were combined to measure a healthy sleep score. A number of healthy sleep factors were defined, along with factors for healthy lifestyle scores. Using Cox proportional hazards regression, computed hazard ratios (HRs) were used to examine the associations between sleep patterns, healthy lifestyles, and the incidence of CRC. Healthy sleep scores were inversely associated with CRC events. The HRs for CRC were 0.90 (95% CI, 0.88–0.92) and 0.95 (95% CI, 0.92–0.98) for a 1-point healthy sleep score increase among males and females. When analyzing sleep components, sleeping 7–8 h/day, no frequent insomnia, no snoring, and no frequent daytime sleepiness were independently associated with a 9%, 14%, 8%, and 14% lower risk of CRC, respectively, whilst healthy lifestyle scores were inversely associated with CRC incidence across all models. Sleep pattern and lifestyle are significantly correlated with CRC risk. The healthier the subject's lifestyle and sleep pattern, the lower their CRC risk. [ABSTRACT FROM AUTHOR]

Background: Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented. Methods: This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern. Results: There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5–6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]. Conclusions: Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives. [ABSTRACT FROM AUTHOR]

Polygenic risk score (PRS) has been shown to be predictive of disease risk such as type 2 diabetes (T2D). However, the existing studies on genetic prediction for T2D only had limited predictive power. To further improve the predictive capability of the PRS model in identifying individuals at high T2D risk, we proposed a new three-step filtering procedure, which aimed to include truly predictive single-nucleotide polymorphisms (SNPs) and avoid unpredictive ones into PRS model. First, we filtered SNPs according to the marginal association p -values (p ≤ 5× 10−2) from large-scale genome-wide association studies. Second, we set linkage disequilibrium (LD) pruning thresholds (r 2) as 0.2, 0.4, 0.6, and 0.8. Third, we set p -value thresholds as 5× 10−2, 5× 10−4, 5× 10−6, and 5× 10−8. Then, we constructed and tested multiple candidate PRS models obtained by the PRSice-2 software among 182,422 individuals in the UK Biobank (UKB) testing dataset. We validated the predictive capability of the optimal PRS model that was chosen from the testing process in identifying individuals at high T2D risk based on the UKB validation dataset (n = 274,029). The prediction accuracy of the PRS model evaluated by the adjusted area under the receiver operating characteristics curve (AUC) showed that our PRS model had good prediction performance [AUC = 0.795, 95% confidence interval (CI): (0.790, 0.800)]. Specifically, our PRS model identified 30, 12, and 7% of the population at greater than five-, six-, and seven-fold risk for T2D, respectively. After adjusting for sex, age, physical measurements, and clinical factors, the AUC increased to 0.901 [95% CI: (0.897, 0.904)]. Therefore, our PRS model could be useful for population-level preventive T2D screening. [ABSTRACT FROM AUTHOR]

Short-term clinical trials have shown the cholesterol-lowering potentials of phytosterols, but their impacts on cardiovascular disease (CVD) remain controversial. This study used the Mendelian randomization (MR) to investigate the relationships between genetic predisposition to blood sitosterol concentration and 11 CVD endpoints, along with the potential mediating effects of blood lipids and hematological traits. Random-effect inverse-variance weighted method was used as the main analysis of MR. Genetic instruments of sitosterol (seven SNPs, F = 253, and R2 = 15.4 %) were derived from an Icelandic cohort. Summary-level data of the 11 CVDs were obtained from UK Biobank, FinnGen, and publicly available genome-wide association study results. Genetically predicted one unit increment in log-transformed blood total sitosterol was significantly associated with a higher risk of coronary atherosclerosis (OR: 1.52; 95 % CI: 1.41, 1.65; n = 667,551), myocardial infarction (OR: 1.40; 95 % CI: 1.25, 1.56; n = 596,436), all coronary heart disease (OR: 1.33; 95 % CI: 1.22, 1.46; n = 766,053), intracerebral hemorrhage (OR: 1.68; 95 % CI: 1.24, 2.27; n = 659,181), heart failure (OR: 1.16; 95 % CI: 1.08, 1.25; n = 1,195,531), and aortic aneurysm (OR: 1.74; 95 % CI: 1.42, 2.13; n = 665,714). Suggestive associations were observed for an increased risk of ischemic stroke (OR: 1.06; 95 % CI: 1.01, 1.12; n = 2,021,995) and peripheral artery disease (OR: 1.20; 95 % CI: 1.05, 1.37; n = 660,791). Notably, blood non-high-density lipoprotein cholesterol (nonHDL-C) and apolipoprotein B mediated about 38–47 %, 46–60 %, and 43–58 % of the associations between sitosterol and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. However, the associations between sitosterol and CVDs were less likely to depend on hematological traits. The study suggests that genetic predisposition to higher blood total sitosterol is linked to a greater risk of major CVDs. Moreover, blood nonHDL-C and apolipoprotein B might mediate a significant proportion of the associations between sitosterol and coronary diseases. [Display omitted] • The causal relationships between blood phytosterols and cardiovascular disease remain to be established. • We found that genetic predisposition to higher blood total sitosterol is linked to increased risks of coronary disease and heart failure. • The associations between sitosterol and coronary diseases were partly mediated by blood nonHDL-C [ABSTRACT FROM AUTHOR]

Reproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. The RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0–1), intermediate lifestyle group (score: 2–3) and healthy lifestyle group (score: 4–5). Each point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. High RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy. [Display omitted] • Novel Reproductive Risk Score finds each point increases cardiovascular disease risk in women. • Healthy lifestyle significantly reduces cardiovascular risk in women with high reproductive risk. • Early management of reproductive risks and healthy living is crucial for women's cardiovascular health. [ABSTRACT FROM AUTHOR]

• Reproductive risk factors have systemic effects on the risk of women's T2D. • Both reproductive and genetic risk are associated with an elevated risk of T2D. • There is a significant reproductive-genetic interaction for women's T2D risk. • Women adhering to healthy reproductive status can protect against T2D genetic risk. To assess synergistic effects of reproductive factors and gene-reproductive interaction on type 2 diabetes (T2D) risk, also the extent to which the genetic risk of T2D can be affected by reproductive risk. 84,254 women with genetic data and reproductive factors were enrolled between 2006 and 2010 in the UK Biobank. The reproductive risk score (RRS) was conducted based on 17 reproductive items, and genetic risk score (GRS) was based on 149 genetic variants. There were 2300 (2.8 %) T2D cases during an average follow-up of 4.49 years. We found a significant increase in T2D risk across RRS categories (P trend < 0.001). Compared with low reproductive risk, high-mediate (adjusted hazard ratio [aHR] 1.38, 95 % CI 1.20–1.58) and high (aHR 1.84, 95 % CI 1.54–2.19) reproductive risk could increase the risk of T2D. We further observed a significant additive interaction between reproductive risk and genetic predisposition. In the situation of high genetic predisposition, women with low reproductive risk had lower risk of T2D than those with high reproductive risk (aHR 0.47, 95 % CI 0.30–0.76), with an absolute risk reduction of 2.98 %. Our novo developed RRS identified high reproductive risk is associated with elevated risk of women's T2D, which can be magnified by gene-reproductive interaction. [ABSTRACT FROM AUTHOR]

The associations between intensity of stair climbing and atherosclerotic cardiovascular disease (ASCVD) and how these vary by underlying disease susceptibility are not fully understood. We aim to evaluate the intensity of stair climbing and risk of ASCVD types and whether these vary with the presence of ASCVD risk factors. This prospective study used data of 458,860 adult participants from the UK Biobank. Information about stair climbing, sociodemographic, and lifestyle factors was collected at baseline and a resurvey 5 years after baseline. ASCVD was defined as coronary artery disease (CAD), ischemic stroke (IS), or acute complications. Associations between flights of stair climbing and ASCVD were examined as hazard ratios (HRs) from Cox proportional hazards models. The modification role of disease susceptibility on such associations was assessed by analyses stratified by levels of genetic risk score (GRS), 10-year risks of ASCVD, and self-reported family history of ASCVD. During a median of 12.5 years of follow-up, 39,043 ASCVD, 30,718 CAD, and 10,521 IS cases were recorded. Compared with the reference group (reported climbing stairs 0 times/day at baseline), the multivariable-adjusted HRs for ASCVD were 0.97 (95% CI, 0.93–1.01), 0.84 (0.82–0.87), 0.78 (0.75–0.81), 0.77 (0.73–0.80) and 0.81 (0.77–0.85) for stair climbing of 1–5, 6–10, 11–15, 16–20 and ≥21 times/day, respectively. Comparable results were obtained for CAD and IS. When stratified by different disease susceptibility based on the GRS for CAD/IS, 10-year risk, and family history of ASCVD, the protection association of stair climbing was attenuated by increasing levels of disease susceptibility. Furthermore, compared with people who reported no stair climbing (<5 times/d) at two examinations, those who climbed stairs at baseline and then stopped at resurvey experienced a 32% higher risk of ASCVD (HR 1.32, 95% CI:1.06–1.65). Climbing more than five flights of stairs (approx 50 steps) daily was associated with a lower risk of ASCVD types independent of disease susceptibility. Participants who stopped stair climbing between baseline and resurvey had a higher risk of ASCVD compared with those who never climbed stairs. [Display omitted] • This large cohort of UK adults demonstrated that climbing more than five flights of stairs daily was associated with over a 20% lower risk of ASCVD. • The associations were broadly concordant in populations with varying susceptibilities to ASCVD. • Participants who discontinued stair climbing between the baseline and resurvey exhibited a higher risk of ASCVD in comparison to those who never engaged in stair climbing. [ABSTRACT FROM AUTHOR]

Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500 g and 2500-2999 g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background The evidence is equivocal on the association between meat consumption and ischemic heart disease (IHD) risk. To what extent the variation of individuals' metabolic responses to the same diet may account for this association is not fully understood. We aim to identify metabolomic signatures characterizing consumption of unprocessed red meat and processed meat and whether such signatures are associated with IHD risk. Methods and Results We conducted a cohort study of 92 246 individuals (mean age, 56.1 years; 55.1% women) using the UK Biobank. During the median follow-up of 8.74 years, 3059 incident IHD events were documented. Unprocessed red meat and processed meat consumption was assessed using a touchscreen dietary questionnaire. Plasma metabolome was profiled by high-throughput nuclear magnetic resonance spectroscopy. Cox proportional hazards regression model was used to test the association of meat consumption with IHD. Genome-wide association analysis and 1-sample Mendelian randomization were performed for metabolomic signatures and causal association of signatures with IHD. Using elastic net regularized regressions, we constructed metabolomic signatures consisting of 157 and 142 metabolites for unprocessed red meat (Spearman correlation coefficient [ r ]=0.223) and processed meat ( r =0.329), respectively. These signatures showed positive associations with incident IHD (red meat related signature: hazard ratio [HR] per SD increment=1.11 [95% CI, 1.06-1.16], P <0.001; processed meat related signature: HR, 1.16 [95% CI, 1.11-1.21], P <0.001). Genome-wide association studies identified 45 and 4 loci, involved in lipid and lipoprotein metabolism, for red and processed meat related signatures. Mendelian randomization showed that there were casual associations of signatures with risk of incident IHD. Conclusions We identify metabolomic signatures that reflect consumption of unprocessed red meat and processed meat, and these signatures are associated with an increased risk of IHD.