Heavy metal exposure and risk of all-cause and cardiovascular mortality in population with cardiovascular-kidney-metabolic syndrome stage 0–3: a cohort study

Dietary magnesium and mortality risk associated with smoking and cadmium: evidence from two national population-based studies

Objective To investigate the associations of blood cadmium levels and smoking status with all-cause and cause-specific mortality and to evaluate whether magnesium intake modifies these associations in two large population-based cohorts. Design Prospective cohort study. Setting US National Health and Nutrition Examination Survey (NHANES, 2003–2018) and UK Biobank (UKB). Participants 35 197 adults from NHANES and 209 615 participants from UKB. Exposures Blood cadmium concentration (NHANES only), self-reported smoking status, dietary magnesium intake and magnesium supplement use. Main outcome measures The main outcomes were all-cause, cardiovascular disease (CVD) and cancer mortality, which were obtained through linkage to national death registries. Results NHANES documented 4412 deaths over a median follow-up of 9.3 years and UKB documented 12 633 deaths over a median follow-up of 13.4 years. In NHANES, compared with adults in the lowest quartile of blood cadmium, those in the highest quartile had higher risks of all-cause (HR (95% CI)1.62 (1.41 to 1.87)), CVD (1.54 (1.19 to 1.98)) and cancer mortality (1.53 (1.14 to 2.05)). Cadmium mediated 31.1% of the effect of smoking on all-cause mortality. High dietary magnesium intake was associated with lower mortality risks, particularly among individuals with high cadmium exposure (HR for all-cause mortality in adults with cadmium ≥median vs <median: 0.81 (0.72 to 0.90) vs 0.91 (0.79 to 1.06); p for additive interaction=0.02) or who smoked (HR for all-cause mortality in smokers vs non-smokers: 0.78 (0.69 to 0.88) vs 0.90 (0.79 to 1.02); p for additive interaction=0.003). No protective association was observed for magnesium supplements. Findings were consistent in UKB, where higher dietary magnesium intake was inversely associated with mortality among smokers. Conclusion Magnesium intake from food, but not supplements, is associated with reduced mortality risk linked to cadmium exposure and smoking. Public health strategies promoting adequate dietary magnesium intake may help mitigate toxicant-related premature mortality.

Associations of dietary inflammatory and antioxidant indices with mortality in adults with cardiovascular–kidney–metabolic syndrome: A mediation analysis

Cardiovascular–kidney–metabolic (CKM) syndrome carries high mortality risk. Whether A Body Shape Index (ABSI), Weight-Adjusted Waist Index (WWI), Systemic Inflammation Response Index (SIRI), and Systemic Immune-Inflammation Index (SII) mediate the associations of Dietary Inflammatory Index (DII) and Composite Dietary Antioxidant Index (CDAI) with mortality in this population remains unknown. We included 21,420 adults with CKM from National Health and Nutrition Examination Survey 1999 to 2018 with mortality follow-up through December 31, 2019. DII and CDAI were calculated from 24-hour dietary recalls. Survey-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cardiovascular mortality, modeling DII and CDAI as continuous variables and tertiles. Restricted cubic splines and 2-piecewise Cox models assessed nonlinearity. Mediation analyses evaluated indirect effects through ABSI, WWI, SIRI, and SII. During follow-up, 3532 all-cause and 1103 cardiovascular deaths occurred. In fully adjusted models, higher DII was associated with increased all-cause mortality (HR per 1-unit increase: 1.06, 95% CI: 1.04–1.09) and cardiovascular mortality (HR: 1.06, 95% CI: 1.02–1.10); the highest versus lowest tertile was associated with HRs of 1.27 (95% CI: 1.16–1.39) and 1.27 (95% CI: 1.08–1.49), respectively. Higher CDAI was associated with lower all-cause and cardiovascular mortality; the highest versus lowest tertile showed HRs of 0.84 (95% CI: 0.77–0.93) and 0.78 (95% CI: 0.65–0.93), respectively. Nonlinearity was observed between CDAI and all-cause mortality (P = .017). The percentage mediated by ABSI, WWI, SIRI, and SII ranged from approximately 4% to 9% for the association with all-cause mortality. In adults with CKM, DII and CDAI were independently associated with mortality outcomes, and ABSI, WWI, SIRI, and SII mediated a modest proportion of the association with all-cause mortality. Further studies are needed to confirm these findings.

Association of accelerometer-measured physical activity and the risk of incident cardiovascular diseases within the AHA cardiovascular-kidney-metabolic syndrome 0–4 framework: a prospective cohort of the UK Biobank

Background Cardiovascular-kidney-metabolic (CKM) syndrome spans stages 0–4, with stage 4 denoting clinical cardiovascular disease (CVD). While individuals in stages 0–3 face elevated incident CVD risk, how different durations of physical activity (PA) associate with this risk remains unclear. Methods This prospective UK Biobank cohort included 88,281 participants aged 37–73 in CKM syndrome stages 0–3, excluding those with baseline CVD. Overall and stage-specific analyzes were performed to evaluate the associations between PA and incident CVD risk. PA was categorized into light PA (LPA) and moderate-to-vigorous PA (MVPA), then divided into quartiles by weekly duration. Multivariable Cox models were used to estimate hazard ratios. An isochronous substitution model using component analysis was used to assess the associated risk differences of replacing LPA with MVPA. Results During a median follow-up of 7.29 years, 7,514 new CVD cases occurred among 88,281 individuals with CKM syndrome stages 0-3. LPA was associated with a lower CVD risk most markedly in stage 2 individuals, with the highest quartile showing a 18% lower risk versus the lowest (HR = 0.82; 95% CI 0.75-0.90). MVPA was associated with a lower CVD risk in stages 1 and 2, with the highest quartile associated with a 42% (HR = 0.58; 95% CI 0.50-0.66) and 33% (HR = 0.67; 95% CI 0.61-0.73) lower risk, respectively. Overall, LPA and MVPA exhibited nonlinear L-shaped relationships across stages 0–3, with overall inflection points at 2,357 (95% CI: 2335-2379) min/week for LPA and 213 (95% CI: 207-219) min/week for MVPA. Specifically, MVPA in stage 3 population exhibited a U-shaped CVD risk curve, increasing beyond 460 (95%CI: 449-472) min/week. In the general population at stages 0-3, when LPA exceeded 2,551 min/week, third-quartile MVPA was associated with a similarly lower risk as the fourth quartile. Substituting MVPA for LPA was associated with further lower risk in stages 1 and 2, while these inverse associations plateaued or declined after reaching 350 min/week in stage 0 and 300 min/week in stage 3, respectively. Conclusion Associations between physical activity and incident CVD differ across CKM stages 0–3. These stage-specific differences for LPA and MVPA warrant further validation to inform future guidelines.

The association between carbon monoxide and cardiovascular-kidney-metabolic syndrome in the Chinese populations: China Health and Retirement Longitudinal Study.

Burden of high blood pressure and associated risk for all-cause and cardiovascular mortality among US young adults.

Background: High blood pressure (BP) in young adults is an underrecognised public health issue with potential long-term health consequences, including increased mortality risk. To examine the prevalence of prehypertension among US young adults and assess its association with all-cause and cardiovascular mortality. Methods: This cohort study utilised data from the National Health and Nutrition Examination Survey (NHANES) 1999-2016. Cox proportional hazards (PHs) regression models were used to estimate hazard ratios (HRs) for mortality. The Fine and Gray subdistribution hazard model was applied to account for competing risks in cardiovascular mortality. Population attributable fractions (PAFs) were calculated to assess the mortality burden associated with prehypertension and hypertension in this population. Prehypertension was defined as a systolic BP (SBP) of 120-139 mm Hg or a diastolic BP (DBP) of 80-89 mm Hg. All-cause and cardiovascular mortality were ascertained through linkage to the National Death Index (NDI) (up to 2019). Results: Among 18,271 participants (mean [SE] age, 28.6 [0.1] years; 49.6% female), the design-weighted prevalence was 23.9% for prehypertension and 14.3% for hypertension. Compared with normotensive individuals, the adjusted HRs for all-cause mortality were 1.82 (95% CI, 1.20-2.74) for prehypertension and 2.39 (95% CI, 1.50-3.81) for hypertension. The HRs for cardiovascular mortality were 1.37 (95% CI, 0.45-4.15) for prehypertension and 4.17 (95% CI, 1.51-11.51) for hypertension. The PAFs for all-cause mortality were 15.1% for individuals with prehypertension and 16.5% for those with hypertension. For cardiovascular mortality, the PAFs were 6.0% for prehypertension and 36.7% for hypertension. Conclusions: In this nationally representative cohort, prehypertension and hypertension were common among US young adults and associated with increased all-cause mortality. These findings highlight the need for early detection and management of high BP in young adults to reduce mortality risk.

Divergent dietary thresholds for all-cause versus cardiovascular mortality in sarcopenia and advanced cardiovascular-kidney-metabolic syndrome: a national prospective cohort study.

INTRODUCTION Sarcopenia and cardiovascular-kidney-metabolic (CKM) syndrome are common comorbidities. We evaluated their cumulative impact on all-cause and cardiovascular mortality, and the modifying effect of a Composite Dietary Antioxidant Index (CDAI). METHODS This prospective study used data from the National Health and Nutrition Examination Survey linked to the National Death Index. Sarcopenia (Foundation for the National Institutes of Health criteria) and CKM syndrome (American Heart Association stages, dichotomised into advanced/non-advanced) defined the primary exposure. Outcomes were all-cause and cardiovascular mortality. Cox models estimated hazard ratios (HRs). Maximally selected rank statistics determined optimal outcome-specific CDAI thresholds. RESULTS Among 8782 participants (median follow-up 131 months), advanced CKM syndrome was associated with sarcopenia (odds ratio 2.29, 95% confidence interval [CI] 1.48-3.53). This study demonstrated a cumulative risk of comorbid advanced CKM syndrome and sarcopenia on mortality, with this group exhibiting the highest risk for all-cause (HR 3.11, 95% CI 1.72-5.61) and cardiovascular (HR 1.80, 95% CI 1.04-3.12) mortality. Furthermore, we identified an inverse relationship between disease burden and protective CDAI thresholds for all-cause mortality, whereas cardiovascular mortality exhibited a distinctly higher threshold. Specifically, the comorbidity group required lower antioxidant intake (CDAI >-3.80) than the non-comorbidity group (CDAI >-1.19) for all-cause mortality. Conversely, cardiovascular mortality required a substantially higher threshold (CDAI >3.04). CONCLUSION Coexisting advanced CKM syndrome and sarcopenia present a significant cumulative mortality risk. Exploratory analyses suggest that this risk may be mitigated by dietary antioxidants, but the protective threshold is context-dependent. Modest dietary improvement was associated with improved all-cause survival in high-risk patients, whereas higher antioxidant intake correlated with better cardiovascular outcomes. These results suggest that precision nutrition strategies may vary depending on the specific health outcome.