@article {689, title = {Calcium channel blocker use and gastrointestinal tract bleeding among older adults.}, journal = {Age Ageing}, volume = {31}, year = {2002}, month = {2002 May}, pages = {217-8}, keywords = {Aged, Antihypertensive Agents, Calcium Channel Blockers, Gastrointestinal Hemorrhage, Geriatric Assessment, Health Services for the Aged, Humans, Hypertension, Prospective Studies, Risk Factors}, issn = {0002-0729}, doi = {10.1093/ageing/31.3.217}, author = {Kaplan, Robert C and Heckbert, Susan R and Koepsell, Thomas D and Rosendaal, Frits R and Furberg, Curt D and Cooper, Lawton S and Psaty, Bruce M} } @article {708, title = {Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Nov 11}, pages = {2325-32}, abstract = {

BACKGROUND: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention.

OBJECTIVE: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP.

METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications.

RESULTS: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37\% at baseline to 49\% in 1999. The 51\% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5\% in 1990 to 51.1\% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased.

CONCLUSIONS: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers--the preferred agents since 1993 according to the recommendations of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure--remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure.

}, keywords = {Age Factors, Aged, Antihypertensive Agents, Awareness, Cohort Studies, Drug Therapy, Female, Health Knowledge, Attitudes, Practice, Humans, Hypertension, Male, Prospective Studies, Time Factors}, issn = {0003-9926}, doi = {10.1001/archinte.162.20.2325}, author = {Psaty, Bruce M and Manolio, Teri A and Smith, Nicholas L and Heckbert, Susan R and Gottdiener, John S and Burke, Gregory L and Weissfeld, Joel and Enright, Paul and Lumley, Thomas and Powe, Neil and Furberg, Curt D} } @article {780, title = {Medications and cardiovascular health in older adults: room for improvement in prevention and treatment.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 May-Jun}, pages = {161-7}, keywords = {Aged, Antihypertensive Agents, Atrial Fibrillation, Cardiovascular Diseases, Diabetes Mellitus, Health Knowledge, Attitudes, Practice, Heart Failure, Humans, Hyperlipidemias, Hypertension, Hypolipidemic Agents, Risk Factors}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02124.x}, author = {Rhoads, Caroline S and Psaty, Bruce M and Olson, Jean L and Furberg, Curt D} } @article {804, title = {Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1648-54}, abstract = {

OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.

DESIGN: Prospective cohort study.

SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina.

PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.

MEASUREMENTS: Adjudicated incident CHF.

RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22\% of men and 8\% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95\% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5\% used alpha antagonists during follow-up, with no observed increase in CHF risk.

CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.

}, keywords = {Adrenergic alpha-Antagonists, Aged, Antihypertensive Agents, Benzothiadiazines, Blood Pressure, Cohort Studies, Diuretics, Female, Heart Failure, Humans, Hypertension, Male, Risk Factors, Sodium Chloride Symporter Inhibitors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52456.x}, author = {Bryson, Chris L and Smith, Nicholas L and Kuller, Lewis H and Chaves, Paulo H M and Manolio, Teri A and Lewis, William and Boyko, Edward J and Furberg, Curt D and Psaty, Bruce M} } @article {825, title = {beta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {18}, year = {2005}, month = {2005 Mar}, pages = {392-7}, abstract = {

BACKGROUND: Common Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) have been associated with hypertension and coronary disease. This analysis of older adults in the Cardiovascular Health Study examined whether these polymorphisms were associated with blood pressure (BP), subclinical atherosclerosis, and, among treated hypertensive individuals, differences in coronary disease risk according to antihypertensive drug class.

METHODS: Altogether, 5249 participants (4441 white and 808 African American, median follow-up time 10.2 years) were genotyped for both polymorphisms. Ankle-arm index (AAI), carotid intima-media thickness (IMT), and brachial flow-mediated dilation were measured cross-sectionally. All estimates were adjusted for ethnicity.

RESULTS: Relative to Gln27 homozygotes, carrying the Glu27 allele was not associated with new-onset hypertension (hazard ratio [HR] = 1.01, 95\% confidence interval [CI] = 0.87 to 1.16), BP control (odds ratio [OR] = 0.97, 95\% CI = 0.89 to 1.06), AAI (mean difference 0.0042 +/- 0.0052), carotid IMT (mean difference 0.0044 +/- 0.02 mm), or brachial flow-mediated dilation (mean difference in baseline diameter -0.028 +/- 0.036 mm; the most marked of three measures). Among treated hypertensive individuals, coronary disease risk was similar in Glu27 carriers relative to Gln27 homozygotes in subgroups defined by use of beta-blockers (HR = 1.09, 95\% CI = 0.64 to 1.87) or other antihypertensive medications (HR = 1.00, 95\% CI = 0.78 to 1.28). Results were similar for the Arg16Gly polymorphism.

CONCLUSIONS: The association of beta(2)AR genotype with coronary disease previously reported in this older adult population is not likely to be explained by BP levels, subclinical atherosclerosis, or antihypertensive treatment. Other measures of vascular response, gene-gene or gene-environment interactions, or characteristics developing earlier in life may mediate the association between beta(2)AR genotype and coronary disease and merit further research.

}, keywords = {African Americans, Antihypertensive Agents, Arteriosclerosis, Coronary Artery Disease, European Continental Ancestry Group, Female, Genotype, Homozygote, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Factors}, issn = {0895-7061}, doi = {10.1016/j.amjhyper.2004.10.014}, author = {Hindorff, Lucia A and Heckbert, Susan R and Psaty, Bruce M and Lumley, Thomas and Siscovick, David S and Herrington, David M and Edwards, Karen L and Tracy, Russell P} } @article {1348, title = {Antihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis.}, journal = {Int J Biostat}, volume = {7}, year = {2011}, month = {2011}, pages = {Article 34}, abstract = {

BACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.

METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.

RESULTS: The mean annual decline in eGFR was 2.41 {\textpm} 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.

CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.

}, keywords = {Aged, Antihypertensive Agents, Cystatin C, Data Interpretation, Statistical, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney, Longitudinal Studies, Male, Models, Statistical}, issn = {1557-4679}, doi = {10.2202/1557-4679.1320}, author = {Odden, Michelle C and Tager, Ira B and van der Laan, Mark J and Delaney, Joseph A C and Peralta, Carmen A and Katz, Ronit and Sarnak, Mark J and Psaty, Bruce M and Shlipak, Michael G} } @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 {6576, title = {Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults.}, journal = {Atherosclerosis}, volume = {235}, year = {2014}, month = {2014 Jul}, pages = {116-21}, abstract = {

BACKGROUND: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress--such as diabetes, chronic kidney disease and aging--where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined.

METHODS: To test the hypothesis that circulating levels of N(ɛ)-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older.

RESULTS: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase=1.11, 95\% confidence interval [CI]=1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke.

CONCLUSIONS: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML{\textquoteright}s value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.

}, keywords = {Aged, Albumins, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Creatinine, Female, Glomerular Filtration Rate, Glycation End Products, Advanced, Humans, Immunoassay, Incidence, Lysine, Male, Oxidative Stress, Proportional Hazards Models, Stroke, Treatment Outcome}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2014.04.013}, author = {Kizer, Jorge R and Benkeser, David and Arnold, Alice M and Ix, Joachim H and Mukamal, Kenneth J and Djouss{\'e}, Luc and Tracy, Russell P and Siscovick, David S and Psaty, Bruce M and Zieman, Susan J} } @article {6875, title = {Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0140496}, abstract = {

BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.

METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).

RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0{\texttimes}10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction >= 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

}, keywords = {African Americans, Aged, Antihypertensive Agents, Cardiovascular Diseases, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Treatment Outcome}, issn = {1932-6203}, doi = {10.1371/journal.pone.0140496}, author = {Bis, Joshua C and Sitlani, Colleen and Irvin, Ryan and Avery, Christy L and Smith, Albert Vernon and Sun, Fangui and Evans, Daniel S and Musani, Solomon K and Li, Xiaohui and Trompet, Stella and Krijthe, Bouwe P and Harris, Tamara B and Quibrera, P Miguel and Brody, Jennifer A and Demissie, Serkalem and Davis, Barry R and Wiggins, Kerri L and Tranah, Gregory J and Lange, Leslie A and Sotoodehnia, Nona and Stott, David J and Franco, Oscar H and Launer, Lenore J and St{\"u}rmer, Til and Taylor, Kent D and Cupples, L Adrienne and Eckfeldt, John H and Smith, Nicholas L and Liu, Yongmei and Wilson, James G and Heckbert, Susan R and Buckley, Brendan M and Ikram, M Arfan and Boerwinkle, Eric and Chen, Yii-Der Ida and de Craen, Anton J M and Uitterlinden, Andr{\'e} G and Rotter, Jerome I and Ford, Ian and Hofman, Albert and Sattar, Naveed and Slagboom, P Eline and Westendorp, Rudi G J and Gudnason, Vilmundur and Vasan, Ramachandran S and Lumley, Thomas and Cummings, Steven R and Taylor, Herman A and Post, Wendy and Jukema, J Wouter and Stricker, Bruno H and Whitsel, Eric A and Psaty, Bruce M and Arnett, Donna} } @article {9372, title = {Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.}, journal = {Am J Hypertens}, volume = {32}, year = {2019}, month = {2019 Nov 15}, pages = {1146-1153}, abstract = {

BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.

METHODS: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP >= 140 mm Hg and/or diastolic BP >= 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL.

RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 {\texttimes} 10-8) and in the race-combined analysis (P = 1.5 {\texttimes} 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95\% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls.

CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.

}, keywords = {Aged, Antihypertensive Agents, Black or African American, Blood Pressure, Case-Control Studies, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, DNA-Binding Proteins, Drug Resistance, Dystrophin-Associated Proteins, Europe, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Myosin Heavy Chains, Myosin Type V, Neuropeptides, Pharmacogenetics, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Transcription Factors, United States, White People}, issn = {1941-7225}, doi = {10.1093/ajh/hpz150}, author = {Irvin, Marguerite R and Sitlani, Colleen M and Floyd, James S and Psaty, Bruce M and Bis, Joshua C and Wiggins, Kerri L and Whitsel, Eric A and St{\"u}rmer, Til and Stewart, James and Raffield, Laura and Sun, Fangui and Liu, Ching-Ti and Xu, Hanfei and Cupples, Adrienne L and Tanner, Rikki M and Rossing, Peter and Smith, Albert and Zilh{\~a}o, Nuno R and Launer, Lenore J and Noordam, Raymond and Rotter, Jerome I and Yao, Jie and Li, Xiaohui and Guo, Xiuqing and Limdi, Nita and Sundaresan, Aishwarya and Lange, Leslie and Correa, Adolfo and Stott, David J and Ford, Ian and Jukema, J Wouter and Gudnason, Vilmundur and Mook-Kanamori, Dennis O and Trompet, Stella and Palmas, Walter and Warren, Helen R and Hellwege, Jacklyn N and Giri, Ayush and O{\textquoteright}donnell, Christopher and Hung, Adriana M and Edwards, Todd L and Ahluwalia, Tarunveer S and Arnett, Donna K and Avery, Christy L} } @article {8511, title = {Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans.}, journal = {Mol Genet Genomic Med}, volume = {7}, year = {2019}, month = {2019 10}, pages = {e00788}, abstract = {

BACKGROUND: Left ventricular (LV) hypertrophy affects up to 43\% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography.

METHODS: We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)-by-drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community-based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta-analyses of main effects of drugs and 2.5~million SNP-by-drug interaction estimates.

RESULTS: We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p~=~0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE-Is with consistent effects across cohorts (smallest p~=~4.7~{\texttimes}~10 , minor allele frequency range 0.09-0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population.

CONCLUSIONS: Our study identified one locus having genome-wide significant SNP-by-drug interaction effect on RWT among dCCB users in comparison to ACE-I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.

}, keywords = {African Americans, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Calcium Channel Blockers, Humans, Observational Studies as Topic, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Sodium Chloride Symporter Inhibitors, Ventricular Dysfunction, Left}, issn = {2324-9269}, doi = {10.1002/mgg3.788}, author = {Do, Anh N and Zhao, Wei and Baldridge, Abigail S and Raffield, Laura M and Wiggins, Kerri L and Shah, Sanjiv J and Aslibekyan, Stella and Tiwari, Hemant K and Limdi, Nita and Zhi, Degui and Sitlani, Colleen M and Taylor, Kent D and Psaty, Bruce M and Sotoodehnia, Nona and Brody, Jennifer A and Rasmussen-Torvik, Laura J and Lloyd-Jones, Donald and Lange, Leslie A and Wilson, James G and Smith, Jennifer A and Kardia, Sharon L R and Mosley, Thomas H and Vasan, Ramachandran S and Arnett, Donna K and Irvin, Marguerite R} }