Prospective associations of genetic susceptibility to high blood pressure and muscle strength with incident cardiovascular disease outcomes

Journal of Hypertension, Год журнала: 2024, Номер unknown

Опубликована: Окт. 15, 2024

Background: This study explored the prospective associations of genetic susceptibility to high blood pressure (BP) and muscle strength with cardiovascular disease (CVD) mortality, incident coronary heart (CHD) stroke. Methods: included 349 085 white British individuals from UK Biobank study. Genetic risk BP was estimated using a weighted polygenic score that incorporated 136 135 nonoverlapping single-nucleotide polymorphisms for systolic diastolic BP, respectively. Muscle assessed hand dynamometer expressed relative fat-free mass. Sex- age-specific tertiles were used classify into three categories. Cox regressions age as underlying timescale fit CVD mortality ( n = 8275), CHD 14 503), stroke 7518). Results: Compared lowest (bottom 20%), highest (top 20%) had greater hazards each outcome. Low associated higher [hazard ratio (HR): 1.51, 95% confidence interval (CI): 1.43–1.59], (HR: 1.16, CI: 1.11–1.21), 1.20, 1.14–1.27), independently confounders predisposition compared strength. Joint analyses revealed 10-year absolute risks outcome lower combined risk, low or medium risk. Conclusion: Individuals who are genetically predisposed but have could major events, those

Язык: Английский

---

Age-specific in the relationship between diastolic blood pressure and the risk of cardiovascular disease: A cohort study of the UK Biobank

Experimental Gerontology, Год журнала: 2024, Номер 198, С. 112635 - 112635

Опубликована: Ноя. 21, 2024

To investigate the effect of optimal diastolic blood pressure (DBP) level on cardiovascular disease (CVD) events, considering different age groups. And nonlinear relationship between DBP and CVD events by were evaluated.

Язык: Английский

---

Genetically Predicted Blood Pressure and Cognition in Midlife: A UK Biobank Study

Hypertension, Год журнала: 2023, Номер 80(10), С. 2112 - 2121

Опубликована: Авг. 17, 2023

BACKGROUND: This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of relationship between measured blood pressure (BP) cognition thus delineate true association two. METHODS: Systolic BP (SBP) diastolic polygenic risk scores (PRSs) were calculated using summary statistics from International Consortium Blood Pressure-Genome Wide Association Study (n=299 024). Adjusted nonlinear mixed-effects regression models used, including natural splines term for BP-PRS with outcomes fluid intelligence, reaction time (RT), composite attention score. Moderating effects age, sex, antihypertensive use assessed in separate models. RESULTS: There 448 575 participants (mean 56.3 years; age range, 37–72 years) included analysis after genetic neurological disease exclusions. Genetic propensity high SBP had an approximately linear worsened intelligence ( P =0.0018). was significantly moderated by <0.0001). By contrast, low predicted worse function =0.0099 =0.0019), PRSs predicting than PRSs. associated considerably RTs, while SBP-PRSs, RT plateaued The relationships sex <0.0001) CONCLUSIONS: impacts on midlife subtle ways differentially affects cognitive domains. While may preserve nontimed tests midlife, it come at trade-off RT.

Язык: Английский

---

Polygenic Risk Scores in the Clinic

Neurology, Год журнала: 2023, Номер 100(15), С. 693 - 695

Опубликована: Янв. 23, 2023

Genome-wide association studies (GWASs) have provided evidence for a polygenic architecture of most common disorders.1 By accumulating power with increasing sample sizes and representation across ancestries, GWASs detected thousands loci the genome associated complex vascular diseases including stroke.2 Polygenic risk scores (PRSs) aggregate this information at an individual level by adding number genetic variants person carries, weighted effect from GWASs. Since their first description, PRSs were considered means toward clinical implementation GWAS-derived data consolidating complicated genomic into simple numerical biomarker representing individual's disease.3 Similar to other traits, ischemic stroke intracerebral hemorrhage are strongly incident events in population-based settings independently factors, such as hypertension.2,4 However, despite innovations PRS construction improvements predictive ability, there has been date no strong evidentiary support use public health practice.5

Язык: Английский

---

Combining pharmacogenetics and patient characteristic polygenic scores to improve outcome prediction for Calcium Channel Blocker treatment

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Фев. 14, 2023

Abstract Background Calcium channel blockers (CCBs) are common antihypertensive medications. Pharmacogenetic variants affect CCB clinical outcomes, although effect sizes modest in community samples. Variation patient characteristics may also predict and variation attributable to relevant polygenic scores is less prone confounding. We aimed test associations between genetically predicted plus pharmacogenetic with outcomes a large cohort. Methods extended our analysis of 32,000 UK Biobank dihydropiridine CCBs treated participants (mean duration 5.9 years) testing 23 variants, where NUMA1 rs10898815 RYR3 rs877087 showed the most robust (for discontinuation heart failure, respectively). calculated for systolic diastolic blood pressures (SBP DBP), body fat mass, waist hip ratio, lean serum calcium, eGFR, lipoprotein A, urinary sodium, liver fibrosis. Outcomes were discontinuation, coronary disease chronic kidney disease. Results For highest risk 20% mass A associated increased risks (Hazard-Ratio (HR)Fat-mass 1.46, 95% CI 1.25-1.70, p=1*10-6; HRLean-mass 1.20, 95%CI 1.04-1.38, p=0.01; HRLipoproteinA 1.29, 1.12 1.48, p= 4*10-4), versus lowest each score respectively. Across cohort, T-allele modestly failure (HR 1.13: 1.02-1.25) non-carriers, but subsets high scores, estimates substantially larger, e.g., females aged 65-70 Relative Risk was 4.4 (95% 1.54-12.4) no T-alleles low scores. 20%, whereas SBP DBP decreased risks. Hazard ratios A-allele (overall HR 1.07: 1.02-1.12) higher 1.17: 1.05-1.29) those mass. Conclusion Polygenic affecting adiposity levels add known predicting key treatment. Combining individual characteristic help personalizing prescribing. What needed, what do we add? previously that patients, modest. Various reportedly outcomes. therefore tested effects using They minimize unmeasured confounders as genotypes invariant since conception reflect lifetime exposure factor. combining improved outcome prediction.

Язык: Английский

---