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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study.
Yu Chen, H, Dina, C, Small, AM, Shaffer, CM, Levinson, RT, Helgadóttir, A, Capoulade, R, Munter, HM, Martinsson, A, Cairns, BJ, et al
European heart journal. 2023;44(21):1927-1939
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Plain language summary
Aortic stenosis (AS) is a form of heart disease that is an abnormal narrowing of the aortic valve in the heart, which restricts blood flow. Although being over the age of 75 appears to increase the risk for development, it is unclear as to who else may be at risk. A better understanding of genetic factors, which may be involved in its development could better help to identify those at risk. This meta-analysis of 10 cohort studies aimed to determine genetic contributors to AS and possible mechanisms involved. The results showed that 15 different gene variations were strongly associated with AS including those in the CELSR2-SORT1, NLRP6, LPA and SMC2 genes. Interestingly some of these genes were also identified in individuals with African and Latin American ancestry. It was concluded that these genes, many of which are associated with hardening of the arteries, altered lipid metabolism, excess storage of fat, and inflammation may all contribute to AS. This study could be used by healthcare professionals to understand that there are specific genetic contributors to the development of AS and that in the future we may be able to target these to identify high-risk individuals and use them in therapeutic management.
Abstract
AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.
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Patient-centered culturally sensitive health care: model testing and refinement.
Tucker, CM, Marsiske, M, Rice, KG, Nielson, JJ, Herman, K
Health psychology : official journal of the Division of Health Psychology, American Psychological Association. 2011;30(3):342-50
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Patient-centred culturally sensitive health care is based on views of culturally diverse patients rather than the views of health care professionals. Empowering patients to share their views concerning culturally sensitive health care is a manifestation of patient centeredness. This study presents an empirical evaluation of a literature-based Patient Centred Culturally Sensitive Health Care Model. The model was designed to explain the link between patient-centred culturally sensitive health care and patients’ treatment adherence, health promoting behaviours, and health outcomes. A total of 229 patients participated in this study, out of which 110 were African American and 119 self-identified as non-Hispanic White American. Results revealed significant links between patient-perceived provider cultural sensitivity and patient adherence to provider recommended treatment regimen variables, with some differences in associations emerging by race/ethnicity. Among both racial/ethnic groups, providing cultural sensitivity had direct effects on trust and satisfaction with care. The effect on care satisfaction was stronger for the African American patients whereas the effect on trust was stronger for the White American patients. Authors conclude that empowering racial/ethnic minorities and individuals with low household incomes to have increased control in patient-provider interactions and in community participatory health promotion interventions may be an important strategy for improving their health and health care utilization.
Abstract
OBJECTIVES This article presents the results of an empirical test of a literature-based Patient-Centered Culturally Sensitive Health Care Model. The model was developed to explain and improve health care for ethnically diverse patients seen in community-based primary care clinics. DESIGN Samples of predominantly low-income African American (n = 110) and non-Hispanic White American (n = 119) patients were recruited to complete questionnaires about their perceived health care provider cultural sensitivity and adherence to their provider's treatment regimen recommendations. MAIN OUTCOME MEASURES Patients completed written measures of their perceived provider cultural sensitivity, trust in provider, interpersonal control, satisfaction with their health care provider, physical stress, and adherence to provider-recommended treatment regimen variables (i.e., engagement in a health promoting lifestyle, and dietary and medication adherence). RESULTS Two-group path analyses revealed significant links between patient-perceived provider cultural sensitivity and adherence to provider treatment regimen recommendations, with some differences in associations emerging by race/ethnicity. CONCLUSION The findings provide empirical support for the potential usefulness of the Patient-Centered Culturally Sensitive Health Care Model for explaining the linkage between the provision of patient-centered, culturally sensitive health care, and the health behaviors and outcomes of patients who experience such care.