Leisure-time physical activity is associated with lower cardiovascular risk in carriers of the rs693 (APOB) and rs1799983 (NOS3) polymorphisms: a cross-sectional study
Aug 2026· Nutrire· Vol 51· 0 citations· 36 references
Abstract
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, especially in low- and middle-income countries. To analyze the interaction between the rs693 (APOB gene) and rs1799983 (NOS3 gene) polymorphisms and leisure-time physical activity (LTPA) and cardiovascular risk (CVR) in adults. This population-based cross-sectional household study in Brazil evaluated CVR using the Framingham Risk Score (FRS), categorized as low (< 5%) or intermediate-to-high (≥ 5%). LTPA was self-reported via a VIGITEL-based questionnaire and categorized per current guidelines. The rs693 and rs1799983 polymorphisms were genotyped by real-time polymerase chain reaction with TaqMan® probes and classified as wild-type homozygous (TT and TT), heterozygous (CT and GT), and mutant homozygous (CC and GG), respectively. A combined genetic risk score was created, in which each genotype received a score from 0 to 2 according to the number of risk alleles. The values were summed, weighted by coefficients estimated in the sample, and subsequently categorized as low or high risk according to the median. Associations between genotypes, LTPA, and CVR were analyzed using univariate and multivariate logistic regression. Among 1,532 participants, 50.6% were male, 46.7% were aged 35–59 years, and 70.3% were physically inactive. Homozygosity for the variant allele was observed in 15.7% of participants for the rs693 polymorphism (CC) and 10.4% for the rs1799983 polymorphism (GG). Physically active individuals with the rs693 variant allele had a lower likelihood of elevated CVR (OR = 0.2; 95% CI: 0.1–0.7; p = 0.007) compared to wild-type homozygotes who were physically inactive. For rs1799983, wild-type homozygous and physically inactive individuals had a higher likelihood of elevated CVR (OR = 2.2; 95% CI: 1.2–3.9; p = 0.011) than physically active individuals with the same genotype. In crude analysis, individuals with high genetic risk but who were physically active had a lower likelihood of elevated CVR (OR = 0.5; 95% CI: 0.2–0.9; p = 0.025) than the low genetic risk and physically active group. Thus, leisure-time physical activity modified the association between rs693 and rs1799983 polymorphisms and CVR, indicating a significant interaction between genetic factors and lifestyle.
Objective To evaluate the association of estimated cardiorespiratory fitness (eCRF) with incident cardiometabolic multimorbidity (CMM) and its potential contribution to CMM risk prediction in an older adult population. Patients and Methods The analysis included 3326 participants from the English Longitudinal Study of Aging (mean age 63 years; 1820 (54.7%) women) who were free of hypertension, cardiovascular disease, diabetes, and stroke at baseline (wave 4; 2008-2009). Estimated CRF was derived using validated nonexercise prediction equations (heart rate-based, body mass index-based, and Nord-Trøndelag Health Study-based eCRF). Incident CMM was defined at wave 10 (2021-2023) as the presence of ≥2 of the following: hypertension, cardiovascular disease, diabetes, or stroke. Multivariable-adjusted odds ratios (ORs) (95% CIs) and discrimination indices were calculated. Results During 12-15 years of follow-up, 197 (5.9%) participants developed CMM. Each eCRF measure reported an inverse linear association with CMM risk. Higher heart rate-based eCRF was associated with lower odds of CMM (per 1- metabolic equivalents (MET) increment: OR=0.78; 95% CI, 0.70-0.87; highest vs lowest tertile: OR=0.42; 95% CI, 0.25-0.69). Similar associations were observed for body mass index-based eCRF (per 1-MET increment: OR=0.78; 95% CI, 0.68-0.89; highest vs lowest tertile: OR=0.42; 95% CI, 0.25-0.70) and Nord-Trøndelag Health Study-based eCRF (per 1-MET increment: OR=0.73; 95% CI, 0.65-0.82; highest vs lowest tertile: OR=0.36; 95% CI, 0.22-0.58). Incorporation of each eCRF measure into a conventional risk prediction model modestly improved discrimination. Conclusion Estimated CRF derived from validated nonexercise equations was similarly and inversely associated with incident CMM in older adults, with all models reporting comparable modest predictive utility.
S. Kunutsor, Reyhaneh Rikhtehgaran, S. Jae et al.· Mayo Clinic Proceedings: Inn...· 0 citations
The association of UCP1 with BMI in the subjects of this study does not agree with the conclusions found in the scientific literature about an increased risk of obesity among G* allele carriers in Caucasian samples, but the associations between UCP2-3 and lipid metabolism parameters in Ob Ugrians are consistent with those reported in Mongoloid populations.
A. I. Kozlov, G. G. Vershubskaya, A. A. Vasileva· Voprosy pitaniia· 0 citations
AIMS
To assess whether self-reported leisure-time physical activity, moderate-to-vigorous leisure-time physical activity, and genetically determined cardiorespiratory fitness are associated with age-related BMI trajectories and incident obesity.
METHODS
We pooled 14 993 adults (30-90 years; 52.7% women; cohorts: REGICOR-ACRISC, ILERVAS, ARTPER) with estimated LTPA (moderate-to-vigorous LTPA [MVLTPA] in REGICOR-ACRISC), genotype, and 120 352 repeated BMI measurements from electronic health records (1990-2024). LTPA was categorised into cohort-specific quartiles; MVLTPA in 0, < 100, < 200, and ≥ 200 METs-min/day. In one-sample Mendelian randomisation analyses, we categorised participants in quartiles of a cardiorespiratory fitness polygenic risk score derived from a large GWAS in UK Biobank. Group-dependent BMI trajectories were modelled using spline mixed-effects models. Obesity onset (first BMI ≥ 30 kg/m2) was analysed with IPW-weighted Kaplan-Meier curves and Cox models.
RESULTS
Higher LTPA was associated with slower BMI increases in ages 30-60 (Q1: +0.120 vs. Q4: +0.075 kg/m2·year), slower declines in ages 70-90 (Q1: -0.143 vs. Q4: -0.123 kg/m2·year), and lower obesity risk (Q4 vs. Q1: HR 0.83, 95% CI 0.72-0.96). Similar trends were observed for MVLTPA. Higher genetically determined cardiorespiratory fitness showed parallel gradients (ages 30-60, Q1: +0.109 vs. Q4: +0.101 kg/m2·year; ages 70-90, Q1: -0.130 vs. Q4: -0.102 kg/m2·year) and lower obesity risk (Q4 vs. Q1: HR 0.66, 0.56-0.78). Associations were present for women and men separately, but were stronger in men.
CONCLUSIONS
Higher LTPA and MVLTPA were associated with more favourable lifelong BMI trajectories, delayed obesity risk, and convergent support from Mendelian randomisation analyses, supporting a causal protective role of physical activity (in both sexes but stronger in men).
J. Hernando-Redondo, A. Camps-Vilaró, R. Elosua et al.· Diabetes, obesity and metabo...· 0 citations
The APOA1 rs670 (−75 G>A) polymorphism has been implicated in lipid metabolism and susceptibility to metabolic syndrome (MetS). However, individual studies have reported inconsistent associations with circulating apolipoprotein A1 (Apo A1) and lipid parameters, and no meta-analysis has comprehensively evaluated these associations stratified by metabolic disorder status. We therefore quantified the associations between APOA1 rs670 and serum Apo A1 and lipid parameters, and determined whether these associations are modified by metabolic disorder status. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026. Eligible studies reported APOA1 rs670 genotype data with quantitative lipid measurements. Forty studies involving 22,175 participants met the inclusion criteria. Pooled effect sizes were estimated as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. This review was registered in PROSPERO (CRD420261333145). A allele carriers had significantly higher serum Apo A1 (SMD, 0.20; p < 0.001) and HDL-C levels (SMD, 0.14; p < 0.001) than GG homozygotes. Subgroup analyses stratified by metabolic disorder status revealed that the associations with Apo A1 (SMD, 0.53 vs. 0.11) and HDL-C (SMD, 0.23 vs. 0.08) were substantially stronger among individuals with metabolic disorders than among metabolically healthy individuals. No significant associations were observed for LDL-C or triglyceride levels. The APOA1 rs670 polymorphism is associated with higher circulating Apo A1 and HDL-C levels, with stronger associations in individuals with metabolic disorders. These findings suggest that metabolic status modifies the phenotypic effects of rs670 on the Apo A1–HDL pathway.
Chien-Yi Chan, Yi-Chen Huang, Ming-Fen Lee et al.· International Journal of Mol...· 0 citations
Stroke pathogenesis in Cardiovascular-Kidney-Metabolic (CKM) is driven by a complex interplay of insulin resistance (IR), systemic inflammation, and adiposity. This study investigated whether integrating adiposity-related measures with the inflammation-IR axis could refine stroke risk prediction in individuals at CKM stage 0–3. A total of 3,348 participants (aged ≥ 45) at CKM stages 0–3 were included from the China Health and Retirement Longitudinal Study (CHARLS). Baseline levels, cumulative exposures, and longitudinal changes were assessed for the original C-reactive protein-triglyceride glucose index (CTI) and seven adiposity-modified CTI indices. Associations with stroke risk were evaluated using Cox proportional hazards models, and potential non-linear relationships were examined using restricted cubic splines. Predictive performance at 3 and 5 years was assessed using fixed-horizon receiver operating characteristic (ROC) analysis. Discrimination was quantified by the area under the curve (AUC) and compared using DeLong’s test, while incremental predictive value was further evaluated using the integrated discrimination improvement (IDI) index. Mediation analysis was used to evaluate the potential role of estimated pulse wave velocity (ePWV) in these associations. Subgroup and sensitivity analyses were conducted to test result robustness, and weighted quantile sum (WQS) regression was performed to determine the relative contribution of components within CTI-related indices. During follow-up, 263 new cases of stroke were observed (7.9%). In fully adjusted models, participants in the highest tertile of all CTI-related indices had significantly increased stroke risk, with hazard ratios (HRs) ranging from 1.92 (95%CI 1.35–2.73) for original CTI to 2.52 (95%CI 1.76–3.61) for CTI-WHtR. K-means clustering of longitudinal changes identified three trajectory groups; compared with the stable group, both markedly increasing and slowly increasing trajectories of CTI and its modified indices were significantly associated with higher stroke risk. In fixed-horizon ROC analyses, the 3-year AUCs for all indices exceeded 0.70. Among baseline indices, CTI-BRI, CTI-BMI, CTI-WC, and CTI-WHtR showed significantly higher AUCs than the original CTI, whereas only CTI-BMI demonstrated a small but significant improvement in IDI over CTI (IDI = 0.0021, 95% CI 0.0004–0.0038; P = 0.012). Among cumulative indices, cumCTI-BMI and cumCTI-WHtR showed significantly higher 3-year AUCs than cumCTI. CTIs-stroke associations were stronger in advanced CKM stages (2–3). Furthermore, component analysis identified CVAI (29.0% in 2012; 29.3% in 2015) as the primary driver of predictive power. ePWV partially mediated the associations between CTI-related indices and incident stroke, with mediation proportions of 12.44%–21.20%. CTI and adiposity-modified CTI indices were independently associated with incident stroke among adults at CKM stages 0–3, especially in advanced CKM stages. Incorporating adiposity-related information provided modest and inconsistent improvement in short-term prediction, with CVAI contributing most prominently and ePWV suggesting a potential arterial stiffness pathway. These findings support the relevance of combined inflammatory, IR, and adiposity burden in stroke risk assessment, but the clinical use of complex composite indices should be balanced against screening feasibility.
Dan Yang, Yan Deng, Z. Su et al.· Cardiovascular Diabetology· 0 citations
Epidemiological and Mendelian randomization studies have reported an inverse relationship between lipoprotein(a) [Lp(a)] concentration and type 2 diabetes (T2D), although findings have not been uniform across studies. We hypothesized that genetic variation at the
LPA
locus may contribute to T2D development beyond circulating Lp(a) concentration alone, and therefore aimed to investigate the association between common
LPA
variation and incident T2D.
We analysed 5058 male participants from the Aragon Workers’ Health Study with approximately 15 years of follow-up. T2D was defined as the presence of antidiabetic treatment or HbA1c ≥ 6.5%. Common
LPA
single-nucleotide variants (SNVs) with a minor allele frequency ≥ 1% were selected. Several weighted
LPA
genetic scores were constructed, with the 15-SNV score defined as the primary
LPA
genetic score and alternative and more restricted scores evaluated in sensitivity analyses. Associations of single
LPA
variants and
LPA
genetic scores with incident T2D were assessed using multivariable logistic regression models adjusted for age, body mass index, ln-transformed Lp(a), and a T2D polygenic risk score. False discovery rate correction was applied to account for multiple testing. Robustness was assessed using leave-one-out analyses and Cox proportional hazards models.
Among 4744 participants free of T2D at baseline, 578 (12.2%) developed incident T2D. Baseline Lp(a) concentrations were lower in participants who developed incident T2D than in those who remained free of T2D (12.6 [5.0–32.5] versus 17.0 [6.1–40.0] mg/dL;
p
< 0.001). No individual
LPA
SNV remained significantly associated with incident T2D. In contrast, the primary 15-SNV
LPA
genetic score was associated with incident T2D after adjustment for measured baseline Lp(a) concentration (odds ratio per one-standard-deviation increase 1.17, 95% confidence interval 1.07–1.29;
p
= 0.001). The 13-SNV, 12-SNV, 10-coding/splice, and 2-SNV raising-Lp(a) scores were also significantly associated with incident T2D after false discovery rate correction. The association with the 15-SNV
LPA
genetic score was supported by leave-one-out and Cox analyses.
A 15-SNV
LPA
genetic score was associated with incident T2D after adjustment for measured baseline Lp(a) concentration and a T2D polygenic risk score. These findings suggest that common
LPA
variation represented by the 15-SNV genetic score may contribute to T2D risk through mechanisms not fully captured by circulating Lp(a) concentration alone.
P. Corredoira, Daniel Bello Álvarez, Itziar Lamiquiz Moneo et al.· Cardiovascular Diabetology· 0 citations