European journal of preventive cardiology最新文献

Aims: Current guidelines fail to adequately guide cardiovascular prevention in young adults, even when a family history of cardiovascular disease (CVD) is known. We aim to assess the feasibility and acceptability of a routine family-based cardiovascular risk assessment in first-degree relatives of individuals with premature coronary artery disease (CAD).

Methods and results: Patients with premature CAD were prospectively asked about pre-existing CVD cases and previous cardiovascular check-ups among their first-degree relatives. They were then encouraged to invite their healthy and naïve to cardiology follow-up relatives to contact the cardiology department for consultation. The primary outcome was the eligibility of relatives for initial cardiovascular evaluation, defined by the absence of previously known CVD or active primary prevention. The cardiovascular status of first-degree relatives was evaluated in the families of 137 probands with premature CAD. Of the 626 identified first-degree relatives, 153 (24.4%) had known CVD, primarily CAD (19.6%). Among the 352 siblings and adult children, 48 (13.7%) were already diagnosed with CVD, 68 (19.3%) were being treated or followed for primary prevention, and 226 (64.2%) were eligible for initial cardiovascular check-up. Within 12 months, 11.1% of eligible relatives initiate screening.

Conclusion: This pilot study revealed (i) a significant familial burden of CVD, (ii) opportunities for proactive primary prevention in two out of three of young relatives, and (iii) challenges in engaging non-symptomatic adults in a cardiovascular screening based on family history.

Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods and results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included. First-degree family members underwent comprehensive FE and decedents with post-mortem DNA were sequenced with a 36 cardiac gene panel for MA. A Bayesian framework for analysis was performed to identify associations. Among 760 SADS decedents (66% male; mean age 31 ± 12 years) the overall diagnostic yield for an inherited cardiac condition was 37% (32-42%) and 9% (6-12%) for FE and MA cohorts. In a subset where both FE and MA were performed the diagnostic yield was 45% (38-61%). The relative risk of an FE diagnosis of long QT syndrome (LQTS) or Catecholaminergic polymorphic ventricular tachycardia (CPVT) vs. remaining unexplained declined by 5.6% [RR 0.94 (0.91-0.98)] and by 11% [RR 0.89 (0.81-0.97)], for each year increase in age. Females were more likely to have a diagnosis by both FE [40% (34-45%) vs. 36% (31-41%)] and MA [15% (10-21%) vs. 6% (3-8%)]. Females [8.1% (4.1-13.4%)], were more likely to be diagnosed with LQTS than males [1.2% (0.2-2.7%)] in the MA cohort.

Conclusion: After a SADS death, the diagnostic yield of comprehensive FE, MA, or both in an expert setting can be up to 45% with a combined approach. Females had higher diagnostic yield than males, most notable with LQTS. CPVT and LQTS diagnoses declined with increasing age. These data highlight the relative utility of FE and MA depending on age and sex for determining underlying diagnoses following SADS deaths.

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.