Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.

We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115).

Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure.

This prospective cohort study evaluated the association between the renin angiotensin aldosterone system genotypes and response to spironolactone in 155 Egyptian patients with heart failure with reduced ejection fraction (HFrEF). Genotype frequencies for AGT rs699 were: CC = 16%, CT = 48%, and TT = 36%. Frequencies for CYP11B2 rs1799998 were: TT = 33%, TC = 50%, and CC = 17%.

Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients From the PEAR Study (Pharmacogenomic Evaluation of Antihypertensive Responses).

Background: Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses).

Genome-wide study of resistant hypertension identified from electronic health records.

Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network.

Large-scale gene-centric analysis identifies polymorphisms for resistant hypertension.

Background: Resistant hypertension (RHTN), defined by lack of blood pressure (BP) control despite treatment with at least 3 antihypertensive drugs, increases cardiovascular risk compared with controlled hypertension. Yet, there are few data on genetic variants associated with RHTN.

Methods And Results: We used a gene-centric array containing ≈50 000 single-nucleotide polymorphisms (SNPs) to identify polymorphisms associated with RHTN in hypertensive participants with coronary artery disease (CAD) from INVEST-GENES (the INnternational VErapamil-SR Trandolapril STudy-GENEtic Substudy).

Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.

We sought to identify novel pharmacogenomic markers for HDL-C response to atenolol in participants with mild to moderate hypertension. We genotyped 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study on the Illumina HumanCVD Beadchip. During PEAR, participants were randomized to receive atenolol or hydrochlorothiazide.