European journal of preventive cardiology最新文献

Sex differences in cardiovascular disease (CVD) are increasingly recognized. These are traditionally attributed to hormonal influences, but recent evidence underscores the potential role of sex chromosomes. This review describes the involvement of sex chromosomes in CVD, through loss of chromosomes, genetic variation, and altered expression. Mosaic loss of the Y chromosome (mLoY) is the most well-characterized mechanism linking sex chromosomes to CVD, with substantial evidence in heart failure. Also, the involvement of mLoY in CVD mechanisms, such as myocardial fibrosis and cardiac macrophage infiltration, both mediated by transforming growth factor beta signalling, has been demonstrated. The mLoY could serve as a biomarker or a causal factor for CVD, with potential implications for risk stratification and therapeutic intervention. X chromosome inactivation escape, which leads to higher expression of specific X-linked genes in females, holds additional promise as an explanation for sex differences in CVD. Animal models have already provided insight into the mechanisms underpinned by this phenomenon, but further research is needed to clarify its impact on cardiovascular outcomes in humans. Overall, this review underscores the complexity of sex chromosome-related mechanisms in CVD and the need to further unravel their role in disease aetiology.

Aims: Cardiovascular disease (CVD) remains a significant public health concern, influenced by both genetic susceptibility and lifestyle factors. Integrating genetic risk information into clinical practice shows promise but has yielded mixed results regarding its impact on CVD prevention and management. This systematic review aimed to assess the impact of providing genetic CVD risk information on health behaviours, psychological outcomes, and risk factors.

Methods and results: Following Joanna Briggs Institute methodology and PRISMA 2020 guidelines, four electronic databases and two trial registries were searched for randomized controlled trials evaluating the impact of genetic risk information on the CVD risk profile. Data were synthesized using a narrative synthesis approach. Of the 3596 articles retrieved, 11 studies were eligible. Genetic risk information showed modest improvements in dietary behaviour but had inconclusive effects on physical activity and medication adherence. Minimal changes in psychological outcomes were noted, including a slight decrease in depression. The impact on traditional risk factors, such as systolic blood pressure and total cholesterol, was also limited. Bias across all studies was noted.

Conclusion: Genetic CVD risk information has limited effects on clinical outcomes and psychological factors, despite its potential to encourage some health behaviour changes. These findings suggest that genetic risk information alone may not be sufficient to significantly reduce cardiovascular risk, highlighting the need for further research to better understand its long-term effects.

Aims: Familial hypercholesterolaemia (FH) is an inherited disease of high LDL cholesterol (LDL-C) caused by defects in LDLR, APOB, APOE, and PCSK9 genes. A pathogenic variant cannot be found in ∼60% of clinical FH patients. Using whole genome sequencing (WGS), we examined genetic determinants of FH.

Methods and results: Whole genome sequencing data generated by the 100 000 Genomes Project (100KGP) included 536 FH patients diagnosed using the FH Simon-Broome criteria. Rare variants in known FH genes were analysed. Genome-wide association study between 443 FH variant-negative unrelated FH cases and 77 275 control participants of the 100KGP was run using high-coverage WGS data. Polygenic risk scores for LDL-C (LDL PRS) and lipoprotein(a) (Lp(a) PRS) were computed. An FH-causing variant was found in 17.4% of FH cases. Genome-wide association study identified the LPA gene locus being significantly associated (P < 1 × 10-8). Familial hypercholesterolaemia variant-negative participants had higher LDL and Lp(a) PRSs in comparison with the controls (P < 1.0 × 10-16 and P < 4.09 × 10-6, respectively). Similar associations were found in the monogenic FH with both LDL and Lp(a) PRSs being higher than in controls (P < 4.03 × 10-4 and P < 3.01 × 10-3, respectively). High LDL PRS was observed in 36.4% of FH variant-negative cases, whereas high Lp(a) PRS in 18.5%, with 7.0% having both high LDL and Lp(a) PRSs.

Conclusion: This genome-wide analysis of monogenic and polygenic FH causes confirms a complex and heterogeneous architecture of hypercholesterolaemia, with the LPA gene playing a significant role. Both Lp(a) and LDL-C should be measured for precision FH diagnosis. Specific therapies to lower Lp(a) should be targeted to those who will benefit most.

Aims: Interleukin-6 (IL-6) levels have been related to increased risk of chronic disease and mortality. Whether genetic IL-6 receptor (IL6R) blockade is associated with lower chronic disease risk or greater longevity is unknown.

Methods and results: The analytic cohort consisted of 38 807 Women's Health Initiative participants who had available genotyping information, of which 23 464 were eligible to survive to 90 years of age through February 192 023. Carrier status of the IL6R variant (rs8192284; p.Asp358Ala) was determined via genotyping. Chronic-disease outcome data were available through 19 February 2023 for coronary heart disease (CHD), heart failure (HF), stroke, and invasive cancer events. Prospective associations of IL6R carrier status with chronic-disease outcomes were assessed with the Cox proportional hazards models, and logistic regression was used to evaluate survival to 90 years of age during follow-up. During a median follow-up of 20 years, 12 181 of 23 464 women (52.0%) survived to age 90. No significant difference in the likelihood of surviving to age 90 was detected between women with 2 alleles of the IL6R gene variant compared to women without any allele (Odds Ratio, 1.00; 95% confidence interval, 0.91-1.09). The risks of CHD, HF, stroke, or cancer did not differ among IL6R variant carriers. High-sensitive C-reactive Protein (hsCRP) levels ≥2 mg/L compared to <2 mg/L were associated with a modest increase in all-cause mortality and CHD risk, independent of IL6R allele carrier status.

Conclusion: Genetic IL6R blockade was not associated with incident chronic-disease risk, including invasive cancer and longevity, in a large, ethnically diverse cohort of postmenopausal women. No significant interaction with hsCRP levels was observed. While pharmacological blockade of IL6R has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease, these long-term data on genetic IL6R blockade do not indicate an altered likelihood for survival to very old age.

Genetic factors can influence cardiovascular disease (CVD) risk through multiple behavioural and physiological mechanisms, including lipid metabolism, blood pressure regulation, and inflammatory responses. The present narrative review examines the impact of physical activity on the relationship between genetic susceptibility and CVD risk. Specifically, we synthesize evidence regarding gene-physical activity interplay and whether individuals with a genetic predisposition for CVD benefit more from physical activity than individuals with more health-favourable genotypes. Most single-gene studies on gene-physical activity interactions have shown that physical activity can significantly reduce CVD risk also in individuals with high genetic predisposition for CVD. Those with higher genetic risk may experience more substantial benefits from physical activity than those with lower genetic risk. Additionally, genetics may play a role in how people respond to exercise and why some people find it harder to adopt a healthy lifestyle. The evidence showed the central role of physical activity in reducing the CVD risk across different genetic profiles, highlighting the need for personalized preventive strategies to optimize cardiovascular health.