Dataset Information

A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.

ABSTRACT: Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32,669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance-weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10(-62)). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07-1.46; P=0.006) and 1.23 (1.05-1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01-1.53; P=0.04) and 1.35 (1.09-1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08-1.40; P=2 × 10(-6)) and 1.26 (1.11-1.44; P=5 × 10(-4)), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.

SUBMITTER: Havulinna AS

PROVIDER: S-EPMC3648219 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.

Havulinna Aki S AS Kettunen Johannes J Ukkola Olavi O Osmond Clive C Eriksson Johan G JG Kesäniemi Y Antero YA Jula Antti A Peltonen Leena L Kontula Kimmo K Salomaa Veikko V Newton-Cheh Christopher C

Hypertension (Dallas, Tex. : 1979) 20130318 5

Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32,669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GR ...[more]

PMID: 23509078

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Project description:ImportanceLittle is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals.ObjectiveTo examine whether daytime and nighttime BP levels measured outside the clinic among African American individuals are associated with cardiovascular disease (CVD) and all-cause mortality independent of BP levels measured inside the clinic.Design, setting, and participantsThis prospective cohort study analyzed data from 1034 African American participants in the Jackson Heart Study who completed ambulatory BP monitoring at baseline (September 26, 2000, to March 31, 2004). Mean daytime and nighttime BPs were calculated based on measurements taken while participants were awake and asleep, respectively. Data were analyzed from July 1, 2017, to April 30, 2019.Main outcomes and measuresCardiovascular disease events, including coronary heart disease and stroke, experienced through December 31, 2014, and all-cause mortality experienced through December 31, 2016, were adjudicated. The associations of daytime BP and nighttime BP, separately, with CVD events and all-cause mortality were determined using Cox proportional hazards regression models.ResultsA total of 1034 participants (mean [SD] age, 58.9 [10.9] years; 337 [32.6%] male; and 583 [56.4%] taking antihypertensive medication) were included in the study. The mean daytime systolic BP (SBP)/diastolic BP (DBP) was 129.4/77.6 mm Hg, and the mean nighttime SBP/DBP was 121.3/68.4 mm Hg. During follow-up (median [interquartile range], 12.5 [11.1-13.6] years for CVD and 14.8 [13.7-15.6] years for all-cause mortality), 113 CVD events and 194 deaths occurred. After multivariable adjustment, including in-clinic SBP and DBP, the hazard ratios (HRs) for CVD events for each SD higher level were 1.53 (95% CI, 1.24-1.88) for daytime SBP (per 13.5 mm Hg), 1.48 (95% CI, 1.22-1.80) for nighttime SBP (per 15.5 mm Hg), 1.25 (95% CI, 1.02-1.51) for daytime DBP (per 9.3 mm Hg), and 1.30 (95% CI, 1.06-1.59) for nighttime DBP (per 9.5 mm Hg). Nighttime SBP was associated with all-cause mortality (HR per 1-SD higher level, 1.24; 95% CI, 1.06-1.45), but no association was present for daytime SBP (HR, 1.13; 95% CI, 0.97-1.33) and daytime (HR, 0.95; 95% CI, 0.81-1.10) and nighttime (HR, 1.06; 95% CI, 0.90-1.24) DBP.Conclusions and relevanceAmong African American individuals, higher daytime and nighttime SBPs were associated with an increased risk for CVD events and all-cause mortality independent of BP levels measured in the clinic. Measurement of daytime and nighttime BP using ambulatory monitoring during a 24-hour period may help identify African American individuals who have an increased cardiovascular disease risk.

Project description:IMPORTANCE:Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart failure, stroke, and myocardial infarction risk. OBJECTIVE:To examine the risk of incident cardiovascular (CV) events among adults with HTN according to 3 SBP levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower than 120 mm Hg. DESIGN, SETTING, AND PARTICIPANTS:A total of 4480 participants with HTN but without prevalent CV disease at baseline (years 1987-1989) from the Atherosclerosis Risk in Communities Study were included. Measurements of SBP were taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent variable and categorized as elevated (?140 mm Hg), standard (120-139 mm Hg), and low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex, diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake. MAIN OUTCOMES AND MEASURES:Incident composite CV events (heart failure, ischemic stroke, myocardial infarction, or death related to coronary heart disease). RESULTS:After a median follow-up of 21.8 years, a total of 1622 incident CV events had occurred. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group (adjusted hazard ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in incident CV event-free survival among those in the standard vs low SBP group (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use or diastolic BP did not significantly affect the results. CONCLUSIONS AND RELEVANCE:Among patients with HTN, having an elevated SBP carries the highest risk for cardiovascular events, but in this categorical analysis, once SBP was below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of incident CV events.

Project description:BackgroundData from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg. Over the past several decades, BP has declined and hypertension control has improved.MethodsWe estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31 856; REGARDS=21 208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study.ResultsOver a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ≥65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm Hg.ConclusionsAlthough higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm Hg at high risk for CVD may be warranted.

Dataset Information

A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.

Publications

A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.

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