Proteomic Signature of BMI and Risk of Cardiovascular Disease.

BACKGROUND: Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). METHODS: A total of 40 089 participants from UK Biobank, free of CVD at baseline, had complete data on proteomic data measured by the Olink assay. A BMI-proteomic score (pro-BMI score) was calculated from 67 pre-identified plasma proteins associated with BMI. RESULTS: A higher pro-BMI score was significantly associated with higher risks of ischemic heart disease (IHD) and heart failure (HF), but not with risk of stroke. Comparing the highest with the lowest quartiles, the adjusted hazard ratio (HR) for IHD was 1.49 (95% CI, 1.32-1.67) (P-trend < 0.001), and the adjusted HR for HF was 1.52 (95% CI, 1.25-1.85) (P-trend < 0.001). Further analyses showed that the association of pro-BMI score with HF risk was largely driven by the actual BMI, whereas the association of the pro-BMI score with IHD risk was independent of actual BMI and waist-to-hip ratio (WHR). The association between pro-BMI score and IHD risk appeared to be stronger in the normal BMI group than other BMI groups (P-interaction = 0.004) and stronger in the normal WHR group than the high WHR group (P-interaction = 0.049). CONCLUSIONS: Higher pro-BMI score is significantly associated with higher IHD risk, independent of actual BMI levels. Our findings suggest that plasma proteins hold promise as complementary markers for diagnosing obesity and may facilitate personalized interventions.

Plasma Levels of Polyols Erythritol, Mannitol, and Sorbitol and Incident Coronary Heart Disease Among Women.

BACKGROUND AND AIMS: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD). METHODS: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses' Health Study. Plasma concentrations of polyols were measured at baseline (1989-90 or 2000-02). Associations of erythritol with cardiometabolic risk factors were also analyzed in the Women's Lifestyle Validation Study (n=728; blood collected in 2010-12). RESULTS: Higher erythritol levels were related to more adverse cardiometabolic risk factor status. The relative risk (RR) for CHD per 1-SD increment was 1.15 [95% CI: 1.04, 1.28] for erythritol and 1.16 [1.05, 1.28] for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had a RR 1.55 [1.13, 2.14] for CHD. The RR in Q4 of erythritol was 1.61 [1.15, 2.24; p=0.006] when hypertension and dyslipidemia were further added to the model; the RR was 1.21 [0.86, 1.70] after adjustment for diabetes. For mannitol/sorbitol, the RR in the Q4 was 1.42 [1.05, 1.91; p=0.022] for CHD in the multivariable-adjusted model including diabetes. CONCLUSIONS: Higher plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavorable association of mannitol/sorbitol, but not erythritol, with CHD risk remained significant independently of diabetes/hyperglycemia.

The present study shows unfavorable associations of circulating erythritol and mannitol/sorbitol with long-term coronary heart disease (CHD) risk even after adjustments for overall diet quality, lifestyle factors, and several other traditional CHD risk factors among women at usual risk. In contrast to mannitol/sorbitol, the association between high erythritol levels and increased CHD risk was no longer significant upon additional inclusion of diabetes in the multivariable-adjusted model. Our findings from the two independent study populations of women without prior CHD suggest endogenous and exogenous erythritol levels are related to unfavorable cardiometabolic risk factor status.

Circulating dimethylguanidino valeric acid, dietary factors, and risk of coronary heart disease.

AIMS: Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)-related foods/nutrients are limited. We investigated whether plasma DMGV was related to risk of incident CHD. We tested associations of DMGV with CHD-related dietary intakes measured by 7-day dietary records and estimated corresponding disease risk. METHODS AND RESULTS: This nested case-control study on the incidence of CHD included 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses' Health Study. Separately, plasma DMGV and CHD-related dietary intakes and cardiometabolic abnormalities were assessed in the Women's Lifestyle Validation Study (WLVS; n=724). Higher plasma DMGV was related to a greater risk of CHD (relative risk [RR] per 1-SD: 1.26 [95% CI: 1.13, 1.40]; P-for-linearity=0.006). Greater intakes of sodium, energy dense-foods, and processed/red meat were related to higher DMGV levels; every 1-SD intake of sodium was associated with ß 0.13 (SE 0.05; p=0.007) for DMGV-Z-scores, which corresponded to a RR of 1.031 [1.016, 1.046] for CHD. High DMGV (the top quartile, Q4) showed a significant RR of 1.60 [1.17, 2.18] after adjusting for diet and lifestyle factors; the RR further adjusting for obesity and hypertension was 1.29 [0.93, 1.79] as compared with the lowest quartile. In both cohorts, greater adiposity and adverse cardiometabolic factor status were significantly related to higher DMGV levels. CONCLUSION: Higher levels of plasma DMGV, a metabolite reflecting unfavorable CHD-related dietary intakes, were associated with an increased risk of CHD. The unfavorable association was attenuated by cardiometabolic risk factor status. Our study underscores the potential importance of plasma DMGV as an early biomarker associated with diet and the long-term risk of CHD among women.

Smoking timing, genetic susceptibility, and the risk of incident atrial fibrillation: a large prospective cohort study.

AIMS: Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with risk of incident AF, and test the modification effect of genetic susceptibility. METHODS AND RESULTS: A total of 305,627 participants with detailed information for time from waking to first cigarette were enrolled from UK Biobank database. Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. Weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13,410 AF cases were documented. Compared to non-smokers, time from waking to the first cigarette showed gradient inverse associations with risk of incident AF (P-trend <0.001). The adjusted hazard ratio related to smoking timing was 1.13 (95% CI: 0.96-1.34) for >120 minutes, 1.20 (95% CI: 1.01-1.42) for 61-120 minutes, 1.34 (95% CI: 1.19-1.51) for 30-60 minutes, 1.43 (95% CI: 1.26-1.63) for 5-15 minutes, and 1.49 (95% CI: 1.24-1.63) for <5 minutes, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF. CONCLUSIONS: Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF.

Our study aimed to analyze the relationship between the time from waking to the first cigarette and incidence of AF, and the modification role of genetic susceptibility.Shorter time from waking to the first cigarette was related to elevated risk of incident atrial fibrillation.Genetic susceptibility to atrial fibrillation strengthened the gradient inverse association of time from waking to the first cigarette with incidence of AF.

Frailty Status, Sedentary Behaviors, and Risk of Incident Bone Fractures.

BACKGROUND: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors. METHODS: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures. RESULTS: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001). CONCLUSIONS: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time.

Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.

AIM: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (pinteraction = 0.017, 0.033 and 0.014, respectively). CONCLUSION: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

Gut-Microbiota-Related Metabolite Phenylacetylglutamine and Risk of Incident Coronary Heart Disease among Women.

CONTEXT: Phenylacetylglutamine (PAGln) is a novel metabolite derived from gut microbial metabolism of dietary proteins, specifically phenylalanine, which may be linked to risks of adverse cardiovascular events. OBJECTIVE: We investigated whether higher plasma levels of PAGln were associated with a greater risk of incident coronary heart disease (CHD) and tested whether adherence to a plant-based diet, which characterizes habitual dietary patterns of animal and plant food intake, modified the associations. METHODS: We examined associations between plasma PAGln and risk of incident CHD over 11-16 years in a nested case-control study of 1520 women (760 incident cases and 760 controls) from the Nurses' Health Study. Separately, we analyzed relations between PAGln and dietary intakes measured through dietary records in the Women's Lifestyle Validation Study (n=725). RESULTS: Higher PAGln levels were related to a greater risk of CHD (p <0.05 for dose-response relationship). Higher PAGln was associated with greater red/processed meat intake and lower vegetable intake (p <0.05 for all). We found a significant interaction between PAGln and adherence to plant-based diet index (PDI) on CHD (Pinteraction=0.008); higher PAGln levels were associated with an increased risk of CHD (relative risk per 1 SD: 1.22 [95% CI: 1.05, 1.41]) among women with low PDI but not among those with high PDI. CONCLUSION: Higher PAGln was associated with higher risk of CHD, particularly in women with dietary patterns of eating more animal foods and fewer plant-based foods. Adherence to plant-based diets might attenuate unfavorable associations between a novel microbial metabolite and CHD risk.

Loneliness, social isolation and incident chronic kidney disease among patients with diabetes.

Background: Individuals with diabetes have a significantly higher risk of developing chronic kidney disease (CKD) and higher levels of social isolation and loneliness compared with those without diabetes. Recently, the American Heart Association highlighted the importance of considering social determinants of health (SDOH) in conjunction with traditional risk factors in patients with diabetes. Aims: To investigate the associations of loneliness and social isolation with incident CKD risk in patients with diabetes in the UK Biobank. Methods: A total of 18 972 patients with diabetes were included in this prospective study. Loneliness and Social Isolation Scales were created based on self-reported factors. An adjusted Cox proportional hazard model was used to investigate the associations of loneliness and social isolation with CKD risk among patients with diabetes. The relative importance in predicting CKD was also calculated alongside traditional risk factors. Results: During a median follow-up of 10.8 years, 1127 incident CKD cases were reported. A higher loneliness scale, but not social isolation, was significantly associated with a 25% higher risk of CKD, independent of traditional risk factors, among patients with diabetes. Among the individual loneliness factors, the sense of feeling lonely emerged as the primary contributing factor to the elevated risk of CKD. Compared with individuals not experiencing feelings of loneliness, those who felt lonely exhibited a 22% increased likelihood of developing CKD. In addition, feeling lonely demonstrated greater relative importance of predicting CKD compared with traditional risk factors such as body mass index, smoking, physical activity and diet. Conclusions: This study indicates the significant relationship between loneliness and CKD risk among patients with diabetes, highlighting the need to address SDOH in preventing CKD in this population.

Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: Findings From UK Biobank.

RATIONALE & OBJECTIVE: Although smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the time smoking is initiated after awakening each day and CKD remains largely unstudied. This study examined the association between this timing and the risk of CKD, and the potential interactions of smoking timing with other risk factors for the occurrence of CKD. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 32,776 participants in the UK Biobank with complete data on the time from waking to the first cigarette and free of prevalent CKD were included. EXPOSURE: Time from waking to the first cigarette. OUTCOME: Incident CKD cases. ANALYTICAL APPROACH: Cox proportional hazards regression was used to investigate the associations between the time smoking is initiated each day and the risk of CKD. The potential interactions of smoking timing with risk factors in relationship to CKD risk were assessed on both multiplicative and additive scales. RESULTS: During a median follow-up period of 12 years, 940 incident CKD cases occurred. Shorter durations of time from waking to the first cigarette were associated with a higher risk of incident CKD (P trend=0.01). Compared with>120 minutes, the adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI, 0.92-1.80) for 61-120 minutes, 1.48 (95% CI, 1.11-1.96) for 30-60 minutes, 1.36 (95% CI, 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI, 1.22-2.37) for<5 minutes, respectively. Furthermore, there was a significant additive interaction and multiplicative interactions between the timing of smoking and a healthy diet score (P for additive interaction=0.01; P for multiplicative interaction = 0.004). LIMITATIONS: Generalizability, possible residual confounding, limiting causal inference. CONCLUSIONS: These findings reveal a significant association between the shorter time from waking to the first cigarette and a higher CKD risk. The magnitude of these associations was greater in the setting of an unhealthy diet. PLAIN-LANGUAGE SUMMARY: This study explored the association of the daily timing of first cigarette smoking and the occurrence of kidney disease. Further, we addressed whether this association was influenced by the quality of the diet. The study found that smoking very soon after waking, especially when combined with a poorer quality diet, was associated with a significantly increased risk of developing chronic kidney disease. This research emphasizes the value of healthier lifestyle choices for kidney health.

Spontaneous miscarriage and social support in predicting risks of depression and anxiety: a cohort study in UK Biobank.

BACKGROUND: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage. OBJECTIVE: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks. STUDY DESIGN: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety. RESULTS: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03). CONCLUSION: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support.

Smoking timing, genetic susceptibility and the risk of incident type 2 diabetes: A cohort study from the UK Biobank.

AIM: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. MATERIALS AND METHODS: A total of 294 815 participants without diabetes from the UK Biobank, including non-smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. RESULTS: During a median follow-up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non-smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend < .001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17-1.81) for more than 2 hours, 1.51 (1.21-1.87) for 1-2 hours, 1.58 (1.34-1.85) for 30-60 minutes, 1.86 (1.57-2.21) for 5-15 minutes and 2.01 (1.60-2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52-2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P-interaction = .51). CONCLUSIONS: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D.

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort.

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in LS BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65 yr.

This study investigated the association between white matter hyperintensities (WMH) and bone health, focusing on BMD, incident fractures and falls. We included 26 410 participants from the UK Biobank and found that a greater WMH volume was associated with BMD in an L-shaped dose­response manner, especially in women and those under 65 yr. Additionally, per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. These findings emphasize the significance of considering brain health when evaluating bone health.

Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial.

BACKGROUND: Distinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. OBJECTIVES: We investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates. METHODS: This study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations. RESULTS: At baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to ß (standard error) -3.3 (1.3), -3.4 (1.3), or -3.8 (1.3) mg/dL, respectively; PFDR < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was ß -4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (PFDR =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet. CONCLUSIONS: Decreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk. This trial was registered at clinicaltrials.gov as NCT00072995.

Degree of joint risk factor control and hazard of mortality in diabetes patients: a matched cohort study in UK Biobank.

BACKGROUND: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. METHODS: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. RESULTS: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41-0.62), 74% (HR 0.26, 95% CI 0.16-0.43) and 38% (HR 0.62, 95% CI 0.44-0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. CONCLUSIONS: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality.

Body composition, lifestyle, and depression: a prospective study in the UK biobank.

BACKGROUND: Obesity has been related to depression and adhering healthy lifestyle was beneficial to lower the risk of depression; however, little is known about the relationship between body composition and fat distribution with depression risk and the influence of body composition and fat distribution on the association of lifestyle and depression. Therefore, we aimed to investigate whether body composition and fat distribution were associated with the adverse events of depression and the relationship between lifestyle and depression. METHODS: We included 330,131 participants without depression at baseline in the UK Biobank (mean age, 56.9 years; 53.83% females). The assessment of depression was sourced from health outcomes across self-report, primary care, hospital inpatient data, and death data. Body composition was determined by bioelectrical impedance. Seven lifestyles (no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, less sedentary behavior, healthy sleep pattern, and appropriate social connection) were used to generate a lifestyle score. RESULTS: During a median of 11.7 years of follow-up, 7576 incident depression occurred. All the body composition measures were positively associated with depression risk, with the Hazard ratios (HR) for the uppermost tertile (T3) versus the lowest tertile (T1) ranging from 1.26 (95% CI: 1.15-1.39) for trunk fat-free mass (TFFM) to 1.78 (1.62-1.97) for leg fat percentage (LFP). In addition, we found significant interactions between fat mass-related indices, especially leg fat mass (LFM) (p = 1.65 × 10-9), and lifestyle score on the risk of depression, for which the beneficial associations of a healthy lifestyle with the risk of depression were more evident among participants with low body fat measurement. CONCLUSIONS: High levels of body composition measures were associated with an increased depression risk. Adverse body composition measures may weaken the link between a healthy lifestyle and a reduced risk of depression.

Ready-to-Eat Food Environments and Risk of Incident Heart Failure: A Prospective Cohort Study.

BACKGROUND: Food environments have been linked to cardiovascular diseases; however, few studies have assessed the relationship between food environments and the risk of heart failure (HF). We aimed to evaluate the association between ready-to-eat food environments and incident HF at an individual level in a large prospective cohort. METHODS: Exposure to ready-to-eat food environments, comprising pubs or bars, restaurants or cafeterias, and fast-food outlets, were individually measured as both proximity and density metrics. We also developed a composite ready-to-eat food environment density score by summing the densities of 3 types of food environments. Cox proportional analyses were applied to assess the associations of each single type and the composite food environments with HF risk. RESULTS: Closer proximity to and greater density of ready-to-eat food environments, particularly for pubs and bars and fast-food outlets (P<0.05 for both proximity and density metric) were associated with an elevated risk of incident HF. Compared with those with no exposure to composite ready-to-eat food environments, participants in the highest density score category had a 16% (8%-25%; P<0.0001) higher risk of HF. In addition, we found significant interactions of food environments with education, urbanicity, and density of physical activity facilities on HF risk (all Pinteraction<0.05); the ready-to-eat food environments-associated risk of HF was stronger among participants who were poorly educated, living in urban areas, and without physical activity facilities. CONCLUSIONS: Exposure to ready-to-eat food environments is associated with a higher risk of incident HF, suggesting the potential importance of minimizing unfavorable food environments in the prevention of HF.

Degree of Risk Factor Control and Incident Cardiovascular Diseases in Patients With Hypertension.

OBJECTIVE: To investigate whether joint risk factor control could reduce the excess risk of cardiovascular disease (CVD) in patients with hypertension. PATIENTS AND METHODS: A total of 75,293 patients with diagnosed hypertension from the UK Biobank study were included, matched with 256,619 nonhypertensive controls, and followed up until May 31, 2021. Seven risk factors were measured to define joint risk factor control, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. RESULTS: Among hypertensive patients, 14% to 24% lower risks of CVD outcomes were associated with each additional risk factor control. In the Cox proportional hazards models, adjusted hazard ratios for patients with 6 or more risk factor controls compared with patients having 2 or less risk factor controls were 0.49 (95% CI, 0.45 to 0.55) for CVD, 0.51 (95% CI, 0.45 to 0.57) for coronary heart disease, 0.48 (95% CI, 0.38 to 0.60) for stroke, and 0.34 (95% CI, 0.26 to 0.44) for CVD mortality. The excess risks of CVD outcomes in patients with hypertension were diminished to nonsignificant or even lower compared with controls if achieving 6 or more risk factor controls. Men experienced stronger protective associations of joint risk factor control on risks of CVD than women (P<.001 for interaction). CONCLUSION: The joint risk factor control is associated with lower risks of CVD, and a high degree of risk factor control may considerably attenuate the excess risk of CVD among patients with hypertension.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets.

OBJECTIVE: MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. METHODS: This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. RESULTS: Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P = 0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (ß[SE] = 0.33 [0.13], P = 0.01 for miR-19a-3p; ß[SE] = 0.3 [0.12], P = 0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction = 0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction = 0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. CONCLUSIONS: In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00072995.

Food Insecurity and Premature Mortality and Life Expectancy in the US.

Importance: Food insecurity has been linked to multiple causes of disease and premature mortality; however, its association with mortality by sex and across racial and ethnic groups remains unknown in the US. Objective: To investigate the associations of the entire range of food security with all-cause premature mortality and life expectancy across racial and ethnic and sex groups in US adults. Design, Setting, and Participants: This cohort study included adults (aged ≥18 years) who participated in the National Health and Nutrition Examination Survey from 1999 to 2018, with linkage to the National Death Index through December 31, 2019. Data analysis was performed from August to November 2023. Exposures: Levels of food security were assessed with the US Department of Agriculture Adult Food Security Survey Module (full, marginal, low, and very low). Main Outcomes and Measures: All-cause premature mortality (death that occurs before age 80 years) and life expectancy. Results: The study included 57 404 adults (weighted mean [SE] age, 46.0 [0.19] years; 51.8% female; 12 281 Black individuals [21.4%]; 10 421 Mexican individuals [18.2%]; 4627 Other Hispanic individuals [8.1%]; 24 817 White individuals [43.2%]; and 5258 individuals of other races, including multiracial [9.2%]). During a median (IQR) of 9.3 (5.0-14.3) years of follow-up, 4263 premature deaths were documented. Compared with the full food security group, the adjusted hazard ratios were 1.50 (95% CI, 1.31-1.71), 1.44 (95% CI, 1.24-1.68), and 1.81 (95% CI, 1.56-2.10) across marginal, low, and very low food security groups, respectively (P < .001 for trend). The corresponding life expectancy at age 50 years in each group was 32.5 (95% CI, 32.4-32.6), 29.9 (95% CI, 28.9-30.9), 30.0 (95% CI, 28.9-31.0), and 28.0 (95% CI, 26.8-29.2) years. Equivalently, adults with marginal, low, or very low food security lived on average 2.6 (95% CI, 1.5-3.7), 2.5 (95% CI, 1.4-3.7), or 4.5 (95% CI, 3.2-5.8) fewer years at age 50 years, respectively, compared with those with full food security. The associations appeared to be stronger in women than in men (hazard ratios comparing very low food security with full food security, 2.29 [95% CI, 1.83-2.86] in women and 1.46 [95% CI, 1.19-1.78] in men; P = .009 for interaction) and stronger in White adults than in Black adults (hazard ratios comparing very low food security with full food security, 2.07 [95% CI, 1.70-2.53] in White adults and 1.33 [95% CI, 1.01-1.75] in Black adults; P < .001 for interaction) or in Hispanic adults (hazard ratios comparing very low food security with full food security, 1.06 [95% CI, 0.71-1.58]; P < .001 for interaction). Conclusions and Relevance: In this cohort study, although the association of food security and life expectancy varied across sex and racial and ethnic groups, overall, lower levels of food security were associated with a higher risk of premature mortality and a shorter life expectancy. The findings of this study highlight the potential importance of improving food security in promoting population health and health equity.

Improvement of Social Isolation and Loneliness and Excess Mortality Risk in People With Obesity.

Importance: Individuals with obesity experience markedly higher levels of social isolation and loneliness than those without obesity, but little is known about whether improvement of social isolation or loneliness might attenuate obesity-related excess risk of mortality. Objective: To investigate whether improvement of social isolation or loneliness is associated with lower obesity-related excess risk of mortality. Design, Setting, and Participants: This cohort study included individuals without cancer or cardiovascular disease (CVD) at baseline from the UK Biobank with follow-up beginning in March 2006 and ending in November 2021. Main Outcomes and Measures: All-cause, cancer-related, and CVD-related mortality were estimated. Results: A total of 398 972 participants were included in this study (mean [SD] age, 55.85 [8.08] years; 220 469 [55.26%] women; 13 734 [3.44%] Asian, 14 179 [3.55%] multiracial, and 363 685 [91.16%] White participants). Overall, 93 357 (23.40%) had obesity, and 305 615 (76.60%) did not. During a median (IQR) follow-up of 12.73 (12.01-13.43) years, a total of 22 872 incident deaths were recorded. Compared with participants with obesity with an index of 2 or greater for social isolation, the multivariable adjusted hazard ratios (HRs) for all-cause mortality were 0.85 (95% CI, 0.79-0.91) and 0.74 (95% CI, 0.69-0.80) for participants with obesity and a social isolation index of 1 and 0, respectively (P for trend < .001); compared with participants with obesity and an index of 2 for loneliness, the HRs and 0.97 (95% CI, 0.89-1.06) and 0.86 (95% CI, 0.79-0.94) for participants with obesity and a loneliness index of 1 and 0, respectively (P for trend < .001). As the index of social isolation and loneliness went from highest to lowest, the HR for all-cause mortality decreased by 36% and 9%, respectively, in people with obesity compared with people without obesity using the multivariable model. Social isolation was ranked higher than loneliness, depression, anxiety, and lifestyle-related risk factors including alcohol, physical activity, and healthy diet for estimating the risks of all-cause mortality, cancer-related mortality, and CVD-related mortality. Conclusions and Relevance: In this cohort study of UK Biobank participants, a lower index of social isolation or loneliness was associated with a decreased risk of all-cause mortality among people with obesity, and improvement of social isolation and loneliness attenuated obesity-related excess risk of all-cause mortality.