Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response.
ABSTRACT: To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP) responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response.We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.
Project description:BACKGROUND:Ambulatory blood pressure (BP) monitoring is the reference standard for out-of-clinic BP measurement. Thresholds for identifying ambulatory hypertension (daytime systolic BP [SBP]/diastolic BP [DBP] ?135/85 mm?Hg, 24-hour SBP/DBP ?130/80 mm?Hg, and nighttime SBP/DBP ?120/70 mm?Hg) have been derived from European, Asian, and South American populations. We determined BP thresholds for ambulatory hypertension in a US population-based sample of African American adults. METHODS:We analyzed data from the Jackson Heart Study, a population-based cohort study comprised exclusively of African American adults (n=5306). Analyses were restricted to 1016 participants who completed ambulatory BP monitoring at baseline in 2000 to 2004. Mean SBP and DBP levels were calculated for daytime (10:00 am-8:00 pm), 24-hour (all available readings), and nighttime (midnight-6:00 am) periods, separately. Daytime, 24-hour, and nighttime BP thresholds for ambulatory hypertension were identified using regression- and outcome-derived approaches. The composite of a cardiovascular disease or an all-cause mortality event was used in the outcome-derived approach. For this latter approach, BP thresholds were identified only for SBP because clinic DBP was not associated with the outcome. Analyses were stratified by antihypertensive medication use. RESULTS:Among participants not taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm?Hg were 134/85 mm?Hg, 130/81 mm?Hg, and 123/73 mm?Hg, respectively. The outcome-derived thresholds for daytime, 24-hour, and nighttime SBP corresponding to a clinic SBP ?140 mm?Hg were 138 mm?Hg, 134 mm?Hg, and 129 mm?Hg, respectively. Among participants taking antihypertensive medication, the regression-derived thresholds for daytime, 24-hour, and nighttime SBP/DBP corresponding to clinic SBP/DBP of 140/90 mm?Hg were 135/85 mm?Hg, 133/82 mm?Hg, and 128/76 mm?Hg, respectively. The corresponding outcome-derived thresholds for daytime, 24-hour, and nighttime SBP were 140 mm?Hg, 137 mm?Hg, and 133 mm?Hg, respectively, among those taking antihypertensive medication. CONCLUSIONS:On the basis of the outcome-derived approach for SBP and regression-derived approach for DBP, the following definitions for daytime, 24-hour, and nighttime hypertension corresponding to clinic SBP/DBP ?140/90 mm?Hg are proposed for African American adults: daytime SBP/DBP ?140/85 mm?Hg, 24-hour SBP/DBP ?135/80 mm?Hg, and nighttime SBP/DBP ?130/75 mm?Hg, respectively.
Project description:Resistant hypertension (RH) may be one of the cause of the plateau in improving the control rate in hypertension (HT) management. The misdiagnosis of RH by clinic blood pressure (BP) is important clinical problem. Aim of the study were to investigate the prevalence of RH by ambulatory blood pressure monitoring (ABPM) and the factor associated with control status of ambulatory BPs.For 1230 subjects taking one or more antihypertensive medication (AHM) enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) registry, the prevalence of RH was calculated which was defined as uncontrolled BP by three AHM classes including diuretic or BP in need of four or more AHM classes. The prevalence determined by clinic versus ambulatory BP was compared.The age was 59.3 ± 12.5 years, and 44.3 % were female (n = 1230). Among them 72 subjects were taking three AHM drugs including diuretics and 105 subjects were taking four or more AHM classes. With uncontrolled daytime ambulatory BP in 41 among 72 subjects, prevalence of RH was 11.9 % (146/1230). By using nighttime BP criteria, there was significant difference in the prevalence of RH for clinic versus nighttime BP (146/177 vs. 159/177, p = 0.0124). For control status of daytime BP, masked uncontrolled BP was 16.9 % and controlled BP with white-coat effect was 14.1 %. For nighttime BP control status, odd ratios for smoking (0.624), drinking (1.512), coronary artery disease (0.604), calcium antagonist (1.705), and loop diuretics (0.454) were all significant.The prevalence itself was 11.9 % by daytime BP and it was significantly higher when using nighttime BP criteria. Control status of daytime BP was misclassified in 31.0 %. Smoking, drinking, coronary artery disease, calcium antagonist, and loop diuretics were associated with nighttime BP control status.
Project description:Home blood pressure (HBP) monitoring is recommended for assessing the effects of antihypertensive treatment, but it is not clear how the treatment-induced changes in HBP compare with the changes in clinic blood pressure (CBP). We searched PubMed using the terms "home or self-measured blood pressure," and selected articles in which the changes in CBP and HBP (using the upper arm oscillometric method) induced by antihypertensive drugs were presented. We performed a systematic review of 30 articles published before March 2008 that included a total of 6794 subjects. As there was significant heterogeneity in most of the outcomes, a random effects model was used for the meta-analyses. The mean changes (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide varieties of differences in the reduction between HBP and CBP. The reductions in CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP; r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring, the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; -12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that included daytime and nighttime systolic BP separately, HBP decreased 15% more than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In conclusion, HBP falls approximately 20% less than CBP with antihypertensive treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls 30% less than home systolic BP.
Project description:Ambulatory blood pressure (BP) correlates more significantly with hypertension-associated cardiovascular mortality and morbidity than BP obtained in the doctor's office. Assessing ambulatory BP, either through 24-h monitoring or through protocolized self-measurement at home, is essential in diagnosing and monitoring patients with hypertension. Several ambulatory BP-derived indicators are related with cardiovascular prognosis. These include 24-h, daytime and nighttime BP measurements, BP measurements obtained through home self-measurement, dipping status, morning surge, and BP variability. The objective of this article was to review the effect of olmesartan-based antihypertensive therapy on the main risk variables obtained when assessing ambulatory BP.
Project description:Importance:Little is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals. Objective:To 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 Participants:This 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 Measures:Cardiovascular 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. Results:A 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 Relevance:Among 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:BACKGROUND:Ambulatory and home blood pressure (BP) monitoring parameters are better predictors of cardiovascular events than are office BP monitoring parameters, but there is a lack of robust data and little information on heart failure (HF) risk. The JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) used the same ambulatory BP monitoring device, measurement schedule, and diary-based approach to data processing across all study centers and determined the association between both nocturnal hypertension and nighttime BP dipping patterns and the occurrence of cardiovascular events, including HF, in patients with hypertension. METHODS:This practitioner-based, nationwide, multicenter, prospective, observational study included patients with at least 1 cardiovascular risk factor, mostly hypertension, and free of symptomatic cardiovascular disease at baseline. All patients underwent 24-hour ambulatory BP monitoring at baseline. Patients were followed annually to determine the occurrence of primary end point cardiovascular events (atherosclerotic cardiovascular disease and HF). RESULTS:A total of 6,359 patients (68.6±11.7 years of age, 48% men) were included in the final analysis. During a mean±SD follow-up of 4.5±2.4 years, there were 306 cardiovascular events (119 stroke, 99 coronary artery disease, 88 HF). Nighttime systolic BP was significantly associated with the risk of atherosclerotic cardiovascular disease and HF (hazard ratio adjusted for demographic and clinical risk factors per 20-mm Hg increase: 1.18 [95% CI, 1.02-1.37], P=0.029; and 1.25 [95% CI, 1.00-1.55], P=0.048, respectively). Disrupted circadian BP rhythm (riser pattern, nighttime BP higher than daytime BP) was significantly associated with higher overall cardiovascular disease risk (1.48 [95% CI, 1.05-2.08]; P=0.024), and especially HF (2.45 [95% CI, 1.34-4.48]; P=0.004) compared with normal circadian rhythm. CONCLUSIONS:Nighttime BP levels and a riser pattern were independently associated with the total cardiovascular event rate, in particular for HF. These findings suggest the importance of antihypertensive strategies targeting nighttime systolic BP. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000020377.
Project description:Background In contrast to the general population, outcome-derived thresholds for diagnosing ambulatory hypertension in pregnancy are not yet available. We aimed to identify and compare outcome-derived ambulatory blood pressure (BP) monitoring thresholds for adverse perinatal outcomes by using approaches related and not related to clinic BP in a southern Chinese population. Methods and Results Ambulatory BP monitoring was performed in a cohort of 1768 high-risk participants in late pregnancy who were not taking antihypertensive medications. Participants were followed for composite maternal (severe complications) and neonatal (pregnancy loss, advanced neonatal care, and small for gestational age) outcomes. Modeling of clinic BP-unrelated approaches revealed a nonlinear threshold effect of ambulatory diastolic BP on the composite outcome, with increased risk for daytime ?79 mm Hg and 24-hour measurement ?76 mm Hg. For other ambulatory BP components showing linear associations with outcome, the following thresholds were identified: 131 mm Hg for daytime systolic, 121 mm Hg for nighttime systolic, 130 mm Hg for 24-hour systolic, and 73 mm Hg for night-time diastolic BP. These thresholds unrelated to clinic BP were lower than the equivalents yielding a similar probability of outcome to clinic BP of 140/90 mm Hg and were comparable with equivalents to clinic BP of 130/80 mm Hg. Conclusions Using an outcome-derived approach unrelated to clinic BP, we identified rounded thresholds to define ambulatory hypertension in at-risk women in late pregnancy in a southern Chinese population as follows: 130/80 mm Hg for daytime, 120/75 mm Hg for nighttime, and 130/75 mm Hg for 24-hour measurement. For wider clinical applicability and to align both nonpregnancy and pregnancy ambulatory BP monitoring with an outcomes-based approach, prospective, multiethnic, international studies from early pregnancy onward will be required.
Project description:BACKGROUND AND OBJECTIVES:Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. RESULTS:Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P=0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P=0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P=0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P=0.10). CONCLUSIONS:These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.
Project description:This review portrays how ambulatory blood pressure (BP) monitoring was established and recommended as the method of choice for the assessment of BP and for the rational use of antihypertensive drugs. To establish much-needed diagnostic ambulatory BP thresholds, initial statistical approaches evolved into longitudinal studies of patients and populations, which demonstrated that cardiovascular complications are more closely associated with 24-hour and nighttime BP than with office BP. Studies cross-classifying individuals based on ambulatory and office BP thresholds identified white-coat hypertension, an elevated office BP in the presence of ambulatory normotension as a low-risk condition, whereas its counterpart, masked hypertension, carries a hazard almost as high as ambulatory combined with office hypertension. What clinically matters most is the level of the 24-hour and the nighttime BP, while other BP indexes derived from 24-hour ambulatory BP recordings, on top of the 24-hour and nighttime BP level, add little to risk stratification or hypertension management. Ambulatory BP monitoring is cost-effective. Ambulatory and home BP monitoring are complimentary approaches. Their interchangeability provides great versatility in the clinical implementation of out-of-office BP measurement. We are still waiting for evidence from randomized clinical trials to prove that out-of-office BP monitoring is superior to office BP in adjusting antihypertensive drug treatment and in the prevention of cardiovascular complications. A starting research line, the development of a standardized validation protocol for wearable BP monitoring devices, might facilitate the clinical applicability of ambulatory BP monitoring.
Project description:The metabolic syndrome is associated with higher ambulatory blood pressure. The authors studied the association of metabolic syndrome and masked hypertension (MHT) among African Americans with clinic-measured systolic/diastolic blood pressure (SBP/DBP) <140/90 mm Hg in the Jackson Heart Study. MHT was defined as daytime, nighttime, or 24-hour hypertension on ambulatory blood pressure monitoring. Among 359 participants not taking antihypertensive medication, the metabolic syndrome was associated with MHT (prevalence ratio, 1.38; 95% confidence interval, 1.10-1.74]). When metabolic syndrome components (clinic SBP/DBP 130-139/85-89 mm Hg, abdominal obesity, impaired glucose, low high-density lipoprotein cholesterol, high triglycerides) were analyzed separately, only clinic SBP/DBP 130-139/85-89 mm Hg was associated with MHT (prevalence ratio, 1.90; 95% confidence interval, 1.56-2.32]). The metabolic syndrome was not associated with MHT among participants not taking antihypertensive medication with SBP/DBP 130-139/85-89 and <130/85 mm Hg, separately, or among participants taking antihypertensive medication (n=393). Ambulatory blood pressure monitoring screening for MHT among African Americans should be considered based on clinic BP, not metabolic syndrome.