@article {1282, title = {Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals.}, journal = {Hypertension}, volume = {57}, year = {2011}, month = {2011 May}, pages = {903-10}, abstract = {

We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29,136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34,433) and the Women{\textquoteright}s Genome Health Study (n=23,019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=4.7{\texttimes}10(-10)), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P=9.5{\texttimes}10(-10)), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P=3.3{\texttimes}10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=3.8{\texttimes}10(-6)), as well as diastolic blood pressure (P=5.0{\texttimes}10(-8)) and hypertension (P=3.7{\texttimes}10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P=3.0{\texttimes}10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions.

}, keywords = {Alleles, Angiotensinogen, Antihypertensive Agents, Blood Pressure, Female, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Male, Pharmacogenetics, Polymorphism, Single Nucleotide, Receptors, Adrenergic, beta-1}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.110.158667}, author = {Johnson, Andrew D and Newton-Cheh, Christopher and Chasman, Daniel I and Ehret, Georg B and Johnson, Toby and Rose, Lynda and Rice, Kenneth and Verwoert, Germaine C and Launer, Lenore J and Gudnason, Vilmundur and Larson, Martin G and Chakravarti, Aravinda and Psaty, Bruce M and Caulfield, Mark and van Duijn, Cornelia M and Ridker, Paul M and Munroe, Patricia B and Levy, Daniel} } @article {7466, title = {Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {37}, year = {2017}, month = {2017 Aug}, pages = {1579-1586}, abstract = {

OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings.

APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15\% and worsening white matter grade in 27\%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95\% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95\% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses.

CONCLUSIONS: Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ.

}, keywords = {Age Factors, Aged, Antihypertensive Agents, Blood Pressure, Cerebral Infarction, Disease Progression, Female, Heart Rate, Humans, Hypertension, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prospective Studies, Pulsatile Flow, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.117.309298}, author = {Leung, Lester Y and Bartz, Traci M and Rice, Kenneth and Floyd, James and Psaty, Bruce and Gutierrez, Jose and Longstreth, W T and Mukamal, Kenneth J} }