Abdominal adiposity may contribute to both general and cardiovascular ageing, yet the extent to which accelerated biological age (BA) at distinct molecular levels mediates these effects has not been fully elucidated.
Three BA measures were constructed using metabolomics (MetaboAge, n=4391), clinical biomarkers (Klemera-Doubal method BA; KDM-BA, n=12 369) and DNA methylation (DNAm PhenoAge, n=980) within the prospective China Kadoorie Biobank and their predictive accuracy for all-cause mortality were evaluated. We explored the potential causal effects of abdominal adiposity, measured by waist-to-hip ratio (WHR) and WHR adjusted for body mass index (WHRadjBMI), on BA acceleration using observational study and Mendelian randomisation. We further investigated the extent to which BA accelerations mediated the effects of abdominal adiposity on cardiovascular ageing (assessed by atherosclerotic cardiovascular disease (ASCVD) incidence and mortality) and general ageing (assessed by all-cause mortality and frailty index).
Both MetaboAge and KDM-BA improved prediction for all-cause mortality beyond chronological age (area under the receiver operating characteristic curve (AUROC) difference: MetaboAge=0.040, KDM-BA=0.012, p<0.001). In observational analyses, abdominal adiposity was associated with accelerated ageing across all three BA clocks, with effect estimates ranging from 0.055 (95% CI 0.038 to 0.073) for the association between WHR and KDM-BA acceleration to 0.107 (0.044 to 0.170) for the association between WHRadjBMI and DNAm PhenoAge acceleration. These associations remained significant in Mendelian randomisation analyses. Mediation analyses revealed that acceleration of MetaboAge and KDM-BA partially explained the effects of abdominal adiposity on cardiovascular ageing (%mediated: 6.0%–25.3%), while all three BA clocks accelerations mediated associations with general ageing assessed by all-cause mortality (%mediated: 17.6%–60.6%), with MetaboAge contributing the largest proportion of mediation. Additionally, KDM-BA acceleration mediated the association between abdominal adiposity and frailty index.
Abdominal adiposity is associated with ageing acceleration across multiple biological domains, especially via metabolic alterations captured by MetaboAge. Our findings demonstrated that targeting abdominal adiposity-related metabolic dysfunction may mitigate age-related conditions.
While we agree with the authors’ emphasis on long-term outcomes and the need for improved patient selection, as well as with the principle that the evolving evidence base in the cardiovascular field necessitates continuous critical appraisal of current clinical practice and guideline recommendations, we would like to highlight that scientific evidence in the field of valvular heart disease is evolving at a pace that often exceeds the update cycles of clinical guidelines. At the time the most...]]>
Left ventricular (LV) strain rates assessed by two-dimensional speckle-tracking echocardiography have exhibited clinical and prognostic significance but remain sparsely used.
We sought to establish age and sex-based normative values of LV strain rates and to assess the prognostic yield of lower limits of normality (LLN).
LV strain rate parameters included global systolic strain rate (GSRs), global early diastolic strain rate (GSRe) and global late diastolic strain rate (GSRa). The primary population consisted of healthy participants free of risk factors from the Copenhagen City Heart Study. The prognostic yield of LLN was assessed against a composite endpoint of cardiovascular death, incident heart failure and acute myocardial infarction using Cox regression in a secondary validation population, regardless of health status.
The healthy population consisted of 1930 subjects with a median age of 46 years (IQR 33, 58), of whom 1193 (61.8%) were female. Median values were –0.97 s–1 (IQR –1.07, –0.90) for GSRs, 1.43 s–1 (1.17, 1.70) for GSRe and 0.77 s–1 (0.60, 0.93) for GSRa. Normative values were determined according to sex and four age intervals. All three parameters differed across sexes, while GSRs was negatively correlated with heart rate; GSRe and GSRa were negatively and positively correlated with age, respectively. GSRa below the sex- and age-appropriate LLN was independently associated with a higher risk of the composite outcome.
This is the largest study to report sex- and age-specific normal values for LV strain rates. The LLNs identified, namely for GSRa, provided independent prognostic information regarding adverse cardiovascular events.
The optimal prosthetic aortic valve replacement (AVR) for long-term outcomes in patients aged 50–70 years remains uncertain. International guidelines differ; contemporary randomised trials are lacking, and use of bioprosthetic valves has increased. This review synthesised evidence comparing efficacy and safety outcomes between valve types in this age group.
A systematic review and meta-analysis of randomised and observational studies comparing mechanical and bioprosthetic AVR in patients aged 50–70 years was conducted. Medline, Embase and the Cochrane Library were searched. The primary outcome was overall survival; secondary outcomes were major bleeding, reoperation and stroke. Data were pooled using inverse variance random-effects meta-analysis and presented as HRs with 95% CIs.
30 studies involving 120 844 patients were included, 29 of which were observational. Mechanical valves were associated with better overall survival (HR 0.88; 95% CI 0.81 to 0.94; p=0.001). Stroke rates did not differ significantly (HR 1.07; 95% CI 0.91 to 1.27; p=0.37). Mechanical valves carried a higher risk of major bleeding (HR 1.60; 95% CI 1.43 to 1.78; p<0.001), while bioprosthetic valves had higher reoperation rates (HR 0.44; 95% CI 0.33 to 0.57; p<0.001).
Drawing largely from observational data, mechanical valves were associated with superior overall survival but increased bleeding due to lifelong anticoagulation. Bioprosthetic valves offer lower bleeding risk but higher reoperation rates from structural degeneration. The growing use of bioprosthetic valves in this age group may lead to more reinterventions in older, more comorbid patients. Contemporary randomised trials are needed to evaluate outcomes with modern valve designs.
CRD42024540272.
Elevated high-sensitivity cardiac troponin (hs-cTn) levels are linked with cardiovascular disease and cognitive impairment, both of which are strong risk factors for late-life dementia (LLD). This study examined the association between hs-cTnI levels below the sex-specific 99th percentile for myocardial injury and the incidence of LLD in older women.
986 community-dwelling women aged ≥70 years without prior LLD and with hs-cTnI <15.6 ng/L (stratified into quartiles) were included from the Perth Longitudinal Study of Ageing Women. The primary outcome was incident LLD events, including LLD hospitalisation or death, over 14.5 years obtained from linked health records. Associations between hs-cTnI and LLD outcomes were explored using multivariable-adjusted Cox models, as part of restricted cubic splines.
At baseline, participants’ mean (±SD) age was 75.2±2.7 years. Over 14.5 years of follow-up, LLD events (n=174, 17.7%), hospitalisations (n=155, 15.7%) and deaths (n=68, 6.9%) were recorded. Compared with those in the lowest quartile (Q1, median 3.1 ng/L), women in the highest quartile of hs-cTnI (Q4, median 7.3 ng/L) had a greater risk of developing LLD-related events (adjusted HR: 1.88, 95% CI: 1.22 to 2.91), hospitalisation (adjusted HR: 1.65, 95% CI: 1.04 to 2.64) and death (adjusted HR: 2.27, 95% CI: 1.13 to 4.59), after adjusting for established cardiovascular and dementia risk factors, including apolipoprotein E (APOE) genotype.
Among older women, hs-cTnI levels below the sex-specific 99th percentile for myocardial injury were associated with an increased risk of LLD events over 14.5 years. These findings suggest that hs-cTnI may identify older women at higher risk of LLD, capturing both cardiovascular and brain health vulnerability in older age.
ACTRN12617000640303.
Sex differences in out-of-hospital cardiac arrest (OHCA) have been studied in adults but remain poorly explored in younger populations. We aimed to assess sex differences in OHCA across age groups to provide a comprehensive overview.
All OHCA occurring between May 2011 and December 2018 in Paris and its suburbs were analysed. Primary outcomes included sex differences in OHCA characteristics and survival to hospital discharge across three age groups: paediatric patients (28 days-18years), young adults (18–35 years) and older adults (≥35 years). Secondary outcomes included aetiology and 1-month survival. Logistic regression was used to identify factors associated with OHCA in females versus males.
Among 18 767 OHCA cases, 6185 (33.0%) were females, 360 (1.92%) were paediatric patients, 1240 (6.61%) young adults and 17 167 (91.5%) older adults.
In paediatric patient, male were older (6.00 vs 2.78 years, p=0.029) and had shorter no-flow times (5.00 vs 10.0 min, p=0.007). Among young adults, OHCA in males occurred more often in public areas (61.9% vs 35.3%, p<0.001) and during sport (6.47% vs 1.53%, p<0.001); females had shorter no-flow time (3.00 vs 5.00 min, p=0.035). In older adults, males were younger (64.3 vs 71.8 years, p<0.001), more shocked (40.2% vs 23.7%, p<0.001) and more commonly managed with amiodarone (16.5% vs 8.11%, p<0.001). OHCA in males occurred more often in public areas (33.9% vs 19.8%, p<0.001) and during sport (1.94% vs 0.30%, p<0.001).
After adjustment, females underwent coronary angiography less often (OR (95% CI) 0.54 (0.46 to 0.64)). Survival to hospital discharge was lower in females across all age groups, reaching statistical significance in older adults (6.23% vs 9.37%, p<0.001).
Sex differences in OHCA characteristics and outcomes were observed across all age groups and became more pronounced with increasing age, consistently indicating a better prognosis for males.