Influence Blood Pressure Response Research Articles

Aerobic exercise training improves nocturnal blood pressure dipping in medicated hypertensive individuals.

The absence of nocturnal blood pressure (BP) reduction at night in hypertensive individuals is associated with an increased cardiovascular risk. The main purpose of the present study was to investigate the effects of an aerobic training intervention on nocturnal BP dipping in medicated hypertensive individuals. At baseline, hypertensive individuals under pharmacological treatment underwent 24-h ambulatory BP monitoring and a morning urine sample to analyze albumin creatinine ratio (UACR). Then, participants were divided into nocturnal dippers ( N = 15; 59 ± 6 years) and nondippers ( N = 20; 58 ± 5 years) according to a day-to-night BP reduction of >10% or <10%, respectively. Next, participants underwent a 3-weekly, 4-month aerobic interval training intervention. Follow-up measurements revealed a reduction in daytime diastolic BP in dippers and nondippers ( Ptime < 0.001), whereas nighttime systolic BP was reduced only in nondippers ( P = 0.004). Regarding dipping pattern, nocturnal systolic BP dipping increased after training in nondippers (5 ± 3 to 9 ± 7%; P = 0.018), whereas in dippers, there was a decrease in nocturnal dipping after training (14 ± 4 to 10 ± 7%, P = 0.016). Nocturnal diastolic BP dipping did not change in nondippers (8 ± 5 to 10 ± 7%; P = 0.273) but decreased in dippers (17 ± 6 to 12 ± 8%; P = 0.004). In addition, UACR was significantly reduced in both groups after training ( Ptime = 0.020). Aerobic exercise training is associated with nocturnal BP dipping as nighttime BP was lower than before the program in medicated hypertensive individuals with an initial nondipping phenotype. The lack of improvement in individuals with a dipping phenotype warrants further investigation to discern whether dipping phenotypes influence BP responses to exercise training.

Effects of Manual Therapies and Resistance Exercise on Postexercise Hypotension in Women With Normal Blood Pressure.

Monteiro, ER, Pescatello, LS, Winchester, JB, Corrêa Neto, VG, Brown, AF, Budde, H, Marchetti, PH, Silva, JG, Vianna, JM, and Novaes, JdS. Effects of manual therapies and resistance exercise on postexercise hypotension in women with normal blood pressure. J Strength Cond Res 36(4): 948-954, 2022-The purpose of this investigation was to examine the acute effects of resistance exercise (RE) and different manual therapies (static stretching and manual massage [MM]) performed separately or combined on blood pressure (BP) responses during recovery in women with normal BP. Sixteen recreationally strength-trained women (age: 25.1 ± 2.9 years; height: 158.9 ± 4.1 cm; body mass: 59.5 ± 4.9 kg; body mass index: 23.5 ± 1.9 kg·m-2; baseline systolic BP median: 128 mm Hg; and baseline diastolic BP median: 78 mm Hg) were recruited. All subjects performed 6 experiments in a randomized order: (a) rest control (CON), (b) RE only (RE), (c) static-stretching exercise only (SS), (d) MM only, (e) RE immediately followed by SS (RE + SS), and (f) RE immediately followed by MM (RE + MM). RE consisted of 3 sets of bilateral bench press, back squat, front pull-down, and leg press exercises at 80% of 10RM. Static stretching and MM were applied unilaterally in 2 sets of 120 seconds to each of the quadriceps, hamstring, and calf regions. Systolic (SBP) and diastolic BP were measured before (rest) and every 10 minutes for 60 minutes following (Post 10-60) each intervention. There were significant intragroup differences for RE in Post-50 (p = 0.038; d = -2.24; ∆ = -4.0 mm Hg). Similarly, SBP intragroup differences were found for the SS protocol in Post-50 (p = 0.021; d = -2.67; ∆ = -5.0 mm Hg) and Post-60 (p = 0.008; d = -2.88; ∆ = -5.0 mm Hg). Still, SBP intragroup differences were found for the MM protocol in Post-50 (p = 0.011; d = -2.61; ∆ = -4.0 mm Hg) and Post-60 (p = 0.011; d = -2.74; ∆ = -4.0 mm Hg). Finally, a single SBP intragroup difference was found for the RE + SS protocol in Post-60 (p = 0.024; d = -3.12; ∆ = -5.0 mm Hg). Practitioners should be aware that SS and MM have the potential to influence BP responses in addition to RE or by themselves and therefore should be taken into consideration for persons who are hypertensive or hypotensive.

Blood pressure responses after resistance exercise session in women living with human immunodeficiency virus/acquired immunodeficiency syndrome.

The aim of this study was to verify blood pressure (BP) responses after a single resistance exercise session in women with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Twelve patients underwent a resisted exercise session. BP, heart rate, and rate pressure product were evaluated before and during 120 min after the session. Mean cardiovascular values before and after the session were similar (P>0.05). Analysis of the individual data revealed that for 120 min after exercise, 5 and 4 patients presented a reduction in systolic and diastolic BP of ≥4 mmHg, respectively. The clinical characteristics of the patients appear to influence BP responses after exercise. Individual data showed that some of the HIV+ women demonstrated a clinically significant decrease in BP. Although a single resistance exercise session does not decrease BP in women with HIV/AIDS, individual data present heterogeneity and individual characteristics seem to influence BP reduction after a single session of resistance exercises.

Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10-8), and the suggestive regions (P<10-5) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein α1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10-4 ). HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment.

Association of the ADRB2 (rs2053044) polymorphism and angiotensin-converting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension.

Hypertension is a risk factor for cardiovascular and kidney disease and is most prevalent in African-American adults. The renin-angiotensin-aldosterone system is integral in blood pressure regulation; angiotensin-converting enzyme inhibitors such as ramipril are first-line treatment options. As decreases in angiotensin result in catecholamine release, β-adrenergic receptor (ADRB) polymorphisms may influence blood pressure response to ramipril. Associations between ADRB polymorphisms and blood pressure response to ramipril were analyzed in the African American Study of Kidney Disease and Hypertension, a randomized clinical trial. A total of 336 participants were included in this analysis. Six polymorphisms were analyzed here: (a) ADRB1 rs1801252 (Ser49Gly) and rs1801253 (Gly389Arg); and (b) ADRB2 rs2053044, rs1042711, rs1042713 (Arg16Gly), and rs1042714 (Gln27Glu). Time to reach a mean arterial pressure (MAP) of 107 mmHg within the first 60 days after randomization was studied using Kaplan-Meier and Cox proportional hazards modeling for univariate and adjusted analyses. Genotypes at rs2053044, upstream from the ADRB2 5' untranslated region, were associated with time to reach target MAP among those randomized to the usual treatment group. Participants with the GG genotype achieved target MAP on average 12.2 days (38.1%) later than in comparison with those with the A allele (P=0.01). After adjusting for covariates, those with the AA/AG genotype had 2.09 greater odds of reaching MAP of 107 mmHg or less within 60 days of treatment in comparison with those with a GG genotype (hazard ratio=2.09, 95% confidence interval=1.21-3.60). Results suggest that ADRB2 rs2053044 genotypes may be a determinant of blood pressure response to ramipril. Additional studies are needed to clarify the effect of rs2053044 and other 5' untranslated region polymorphisms on gene expression and blood pressure response to angiotensin-converting enzyme inhibitors.

Association of vitamin D status and blood pressure response after renal denervation

Vitamin D deficiency is associated with hypertension; however, it is unclear whether vitamin D influences therapeutic blood pressure reduction. Renal sympathetic denervation (RDN) reduces blood pressure in resistant hypertension. We hypothesized that vitamin D might influence blood pressure response to RDN. Vitamin D was measured in 101 patients with resistant hypertension undergoing RDN. The associations between vitamin D status and systolic blood pressure (SBP) reduction 6 months after RDN were analyzed. Mean office SBP at baseline was 171.5 ± 2 mmHg. After RDN, mean office SBP was reduced by 28.4 ± 2.3 mmHg (p = 0.007). 85 patients (84.2 %) had SBP reductions >10 mmHg (responders). Vitamin D concentrations were lower in non-responders as compared to responders (9.9 ± 4.5 vs. 13.7 ± 7.4 ng/ml, p = 0.008). Non-responders (n = 16, 15.8 %), more often had a vitamin D concentration below the median as compared to responders (81 vs. 46 %, p = 0.013). The percentage of patients with normal vitamin D concentrations increased with increasing tertiles of SBP reduction (p for trend = 0.020). In patients with vitamin D concentrations below the median, SBP reduction was lower as compared to patients with a vitamin D concentration above the median (23.5 ± 3.2 vs. 33.7 ± 3.2 mmHg, p = 0.026). Baseline vitamin D concentrations correlated with SBP reduction (r = 0.202, p = 0.043). In patients with resistant hypertension, low vitamin D concentrations were associated with a decreased SBP response and a higher rate of non-response.

Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide

To identify novel genes influencing blood pressure response to thiazide diuretic therapy for hypertension, we conducted genome-wide association meta-analyses of ≈1.1 million single-nucleotide polymorphisms in a combined sample of 424 European Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=228) and the Genetic Epidemiology of Responses to Antihypertensive study (n=196). Polymorphisms associated with blood pressure response at P<10(-5) were tested for replication of the associations in independent samples of hydrochlorothiazide-treated European hypertensives. The rs16960228 polymorphism in protein kinase C, α replicated for same-direction association with diastolic blood pressure response in the Nordic Diltiazem study (n=420) and the Genetics of Drug Responsiveness in Essential Hypertension study (n=206), and the combined 4-study meta-analysis P value achieved genome-wide significance (P=3.3 × 10(-8)). Systolic or diastolic blood pressure responses were consistently greater in carriers of the rs16960228 A allele than in GG homozygotes (>4/4 mm Hg) across study samples. The rs2273359 polymorphism in the GNAS-EDN3 region also replicated for same-direction association with systolic blood pressure response in the Nordic Diltiazem study, and the combined 3-study meta-analysis P value approached genome-wide significance (P=5.5 × 10(-8)). The findings document clinically important effects of genetic variation at novel loci on blood pressure response to a thiazide diuretic, which may be a basis for individualization of antihypertensive drug therapy and identification of new drug targets.

Social support is associated with blood pressure responses in parents caring for children with developmental disabilities

The present study tested whether parents caring for children with developmental disabilities would have higher blood pressure compared to parents of typically developing children (controls). It also examined the psychosocial factors underlying this observation. Thirty-five parents of children with developmental disability and thirty controls completed standard measures of perceived stress, child challenging behaviours and social support and wore an ambulatory blood pressure (BP) monitor throughout the day, for one day. Relative to controls, parents caring for children with developmental disabilities reported poorer psychosocial functioning and had a higher mean systolic BP. Of the psychosocial predictors, only social support was found to be predictive. Moreover, variations in social support accounted for some of the between group differences with the β for parental group attenuated from .42 to .34 in regression analyses. It appears that social support may influence blood pressure responses in parental caregivers. Finally, our findings underscore the importance of providing psychosocial interventions to improve the health of family caregivers.

Genomic Association Analysis Identifies Multiple Loci Influencing Antihypertensive Response to an Angiotensin II Receptor Blocker

To identify genes influencing blood pressure response to an angiotensin II receptor blocker, single nucleotide polymorphisms identified by genome-wide association analysis of the response to candesartan were validated by opposite direction associations with the response to a thiazide diuretic, hydrochlorothiazide. We sampled 198 white and 193 blacks with primary hypertension from opposite tertiles of the race-sex-specific distributions of age-adjusted diastolic blood pressure response to candesartan. There were 285 polymorphisms associated with the response to candesartan at P<10(-4) in whites. A total of 273 of the 285 polymorphisms, which were available for analysis in a separate sample of 196 whites, validated for opposite direction associations with the response to hydrochlorothiazide (Fisher χ(2) 1-sided P=0.02). Among the 273 polymorphisms, those in the chromosome 11q21 region were the most significantly associated with response to candesartan in whites (eg, rs11020821 near FUT4, P=8.98 × 10(-7)), had the strongest opposite direction associations with response to hydrochlorothiazide (eg, rs3758785 in GPR83, P=7.10 × 10(-3)), and had the same direction associations with response to candesartan in the 193 blacks (eg, rs16924603 near FUT4, P=1.52 × 10(-2)). Also notable among the 273 polymorphisms was rs11649420 on chromosome 16 in the amiloride-sensitive sodium channel subunit SCNN1G involved in mediating renal sodium reabsorption and maintaining blood pressure when the renin-angiotensin system is inhibited by candesartan. These results support the use of genomewide association analyses to identify novel genes predictive of opposite direction associations with blood pressure responses to inhibitors of the renin-angiotensin and renal sodium transport systems.

Abstract P232: Common Variants of the Estrogen Receptor 1 Gene Predict Decreased Blood Pressure Salt-Sensitivity in Men: The GenSalt Study

Previous reports have documented increased blood pressure (BP) salt-sensitivity in women compared to men, suggesting that genes encoding sex hormones could influence BP response to sodium. In the current study, we examined the association between 799 single nucleotide polymorphisms (SNPs) in 44 genes involved in sex hormone biosynthesis, bioavailability and metabolism for their association with BP responses to sodium intervention separately in men and women. A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding-study (307.8 mmol sodium/day) was conducted among 1,906 participants from 633 Han Chinese families. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. Additive associations between each SNP and BP responses to low and high-sodium interventions were assessed using a mixed linear regression model to account for familial dependencies. Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453 and rs9383951. For example, men with genotypes C/C, C/T, and T/T of rs9397453 had respective mean DBP responses [95% confidence intervals (CI)] of: -2.67 (-3.13, -2.22), -1.23 (-1.98, -0.48), and 0.08 (-2.31, 2.47) mmHg to low-sodium intervention [p=1×10 -4 ; false discovery rate (FDR)-q=0.04]; and 1.46 (1.03, 1.89), 0.19 (-0.54, 0.91), and -1.10 (-2.82, 0.61) mmHg to high-sodium intervention (p=2×10 -4 ; FDR-q=0.04). In addition, mean SBP responses (95% CI) were: -5.70 (-6.19, -5.20), -4.34 (-5.37, -3.31), and -2.65 (-5.15, -0.16) mmHg, respectively, for low-sodium intervention (p=2×10 -3 ; FDR-q=0.17); and 4.56 (4.12, 4.99), 3.47 (2.63, 4.30), and 1.97 (-0.49, 4.43) mmHg, respectively, for high-sodium intervention (p=3×10 -3 ; FDR-q=0.40). ESR1 variants were not associated with BP responses in women, with highly significant genotype-gender interactions noted. In summary, we identified strong, consistent associations between genetic variants in the ESR1 gene and decreased salt-sensitivity in men. Although replication of these findings is needed, our results support a role for sex-hormones in the etiology of this complex trait. Funding(This research has received full or partial funding support from the American Heart Association, National Center)

Genetic variants in the renin-angiotensin system and blood pressure reactions to the cold pressor test.

The purpose of this study was to examine the association between genetic variants in the renin-angiotensin system and blood pressure (BP) responses to the cold pressor test (CPT). The CPT was conducted among 1998 Han Chinese participants. BP measurements were obtained before and after the CPT using a standard sphygmomanometer according to a standard protocol. The association between SNP genotypes and BP responses to the CPT was assessed using a mixed linear model. Of 68 SNPs genotyped in six renin-angiotensin system genes, two were strongly associated with DBP responses to CPT (P ≤ 0.001; false discovery rate q value < 0.05): rs2006765 and rs943580 in the angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT homozygotes had a significantly decreased DBP response to the CPT. For participants with the TT genotype, percentage DBP responses were 5.68% (4.25-7.10%), compared to corresponding responses of 9.17% (8.66-9.68%) among participants with the CC+CT genotype. In addition, SNP rs4681443 of the angiotensin type 1 receptor (AGTR1) gene was significantly associated with percentage SBP responses to CPT (P ≤ 0.001; q-value <0.05). Briefly, our study identified variants in the AGT and AGTR1 genes that may influence BP responses to CPT in the Han Chinese population. These results show that genetic variants in the renin-angiotensin system play an important role in BP responses to CPT and, therefore, in predicting future hypertension.

Cardiovascular disease risk factors and blood pressure response during exercise in healthy children and adolescents: The European Youth Heart Study

Raised blood pressure (BP) response during exercise independently predicts future hypertension. Subjects with higher BP in childhood also have elevated BP later in life. Therefore, the factors related to the regulation of exercise BP in children needs to be well understood. We hypothesized that physiological cardiovascular disease (CVD) risk factors would influence BP response during exercise in children and adolescents. This is a cross-sectional study of 439 Danish third-grade children and 364 ninth-grade adolescents. Systolic blood pressure (SBP) was measured with sphygmomanometer during a maximal aerobic fitness test. Examined CVD risk factors were high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglyceride, homeostasis model of assessment of insulin resistance (HOMA-IR) score, body mass index (BMI), waist circumference, and aerobic fitness. A random effect model was used to test the hypotheses. In boys, HOMA-IR score and BMI were positively related to SBP response during exercise (β = 1.03, P = 0.001, and β = 0.58, P = 0.017, respectively). The effects sizes of HOMA-IR score and BMI and the significance levels only changed slightly (β = 0.91, P = 0.004, and β = 0.43, P = 0.08, respectively) when the two variables were added in the same model. A significant positive association was observed between aerobic fitness and SBP response in girls (β = 3.13 and P = 0.002). HOMA-IR score and BMI were found to be positively related to the SBP response in male children and youth. At least partly, adiposity and insulin sensitivity seem to influence exercise SBP through different mechanisms. The positive relationship observed between aerobic fitness and SBP response in girls remains unexplainable for us, although post hoc analyses revealed that it was the case in the ninth graders only.

Blood pressure response to potassium supplementation is associated with genetic variation in endothelin 1 and interactions with E selectin in rural Chinese

Although beneficial effects of potassium intake on blood pressure (BP) are well established, little is known about genetic factors that underlie interindividual variability in BP response to dietary potassium. In a previous study, we reported the first evidence for significant heritabilities for BP response in a dietary intervention study in rural Chinese. In this report, we extend our genetic studies to examine associations with polymorphisms in genes in vascular endothelial pathways. We genotyped study participants for 23 single nucleotide polymorphisms (SNPs) in endothelin 1 (EDN1), nitric oxide synthase 3, and E selectin (SELE). We tested 17 of these SNPs for associations with BP response to potassium supplementation in 1843 participants. Association tests used population-based [generalized estimation equation (GEE)] and family-based (quantitative transmission disequilibrium test) methods, as well as tests for gene-by-gene (GxG) interaction (generalized multifactor dimensionalilty reduction and GEE). Single SNP analysis identified significant associations for several SNPs in EDN1 with multiple measures of BP response to potassium supplementation. The cumulative effects of the minor EDN1 alleles that showed significant associations were to reduce measures of BP response by 0.5-0.9 mmHg. We found significant evidence for effects of GxG interactions between EDN1 and SELE, even in the absence of individual associations with SELE variants. Our results implicate variability in EDN1 and SELE as genetic factors that influence BP response to potassium intake. Although such epidemiological studies do not allow direct determination of physiologic mechanisms, our findings of joint effects identify EDN1 and SELE as targets for functional studies to determine their interactions in BP response to potassium intake.

Association of Genetic Variants in the Apelin-APJ System and ACE2 With Blood Pressure Responses to Potassium Supplementation: The GenSalt Study

Genetic factors may influence blood pressure (BP) responses to dietary potassium intake. We examined the association of genetic variants in the apelin-APJ system and angiotensin-converting enzyme 2 (ACE2) with BP responses to potassium supplementation. We conducted a 7-day potassium supplementation (60 mmol/day) intervention among 1,906 Chinese adults who participated in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Tag single-nucleotide polymorphisms (SNPs) based on HapMap data and potential functional SNPs were selected in the APLN, APLNR, and ACE2 genes. Because the ACE2 and APLN genes are located on the X chromosome, men and women were analyzed separately. In women, SNP rs2235306 in the APLN gene was significantly associated with diastolic BP (DBP) response to potassium supplementation (P = 0.0009). The DBP responses (95% confidence interval (CI)) among those with genotypes T/T, T/C, and C/C were -2.22 (-2.74, -1.70), -1.69 (-2.20, -1.19), and -0.81 (-1.54, -0.09) mm Hg, respectively. In men, SNP rs4646174 of the ACE2 gene was significantly associated with systolic BP (SBP), DBP, and mean arterial pressure (MAP) responses to potassium supplementation (P = 0.0001, P = 0.001, and P = 3.0 x 10(-6), respectively). The SBP, DBP, and MAP responses (95% CI) were -0.79 (-2.27, 0.69) vs. -3.53 (-3.94, -3.12), 1.07 (-0.34, 2.49) vs. -1.06 (-1.43, -0.69), and 0.44 (-0.60, 1.48) vs. -1.89 (-2.22, -1.55) mm Hg among men with minor G allele compared to those with major C allele of rs4646174, respectively. Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.

Arg347Cys polymorphism of α1A-adrenoceptor gene is associated with blood pressure response to nifedipine GITS in Chinese hypertensive patients

Our objectives were to evaluate whether polymorphisms in the alpha1A- and beta2-adrenoceptor genes influence blood pressure response to nifedipine gastrointestinal therapeutic system (GITS). Hypertensive patients received daily treatment with an oral dosage of 30 mg nifedipine GITS for 16 days. Genotypes of the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene and the Arg16Gly and Gln27Glu polymorphisms in the beta2-adrenoceptor gene were determined by TaqMan single-nucleotide polymorphism genotyping assay. The sixteenth-day steady-state plasma concentration of nifedipine was measured using HPLC with UV detection. Multivariate linear regression was performed in a total of 447 patients to evaluate the effects of these polymorphisms on blood pressure response to nifedipine GITS. Patients carrying the Cys347 allele of the alpha1A-adrenoceptor gene had a greater systolic blood pressure reduction than did those carrying two Arg347 alleles of the alpha1A-adrenoceptor gene (32.5+/-14.0 versus 27.3+/-15.5 mm Hg, respectively, P=0.006). However, diastolic blood pressure reduction was not associated with the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene. In addition, no significant associations were observed between blood pressure reduction and two polymorphisms in the beta2-adrenoceptor gene. Our data suggest that the Arg347Cys polymorphism in the alpha1A-adrenoceptor gene may be used to predict blood pressure response to nifedipine GITS in Chinese hypertensive patients.

I040 Individual characteristics influence blood pressure response to antihypertensive drugs

Antihypertensive treatment decreases cardiovascular risk mostly through blood pressure reduction. The current prescription strategy for the choice of drug between the five main antihypertensive classes relies upon intuitive or random choice by the physician. The objective of our analysis was to explore whether systolic blood pressure (SBP) reduction with diuretics, beta-blockers (BB), and calcium channel blockers (CCB), was related to the baseline individual characteristics, and quantify these potential associations. We used data from 32767 patients recruited in five randomized placebo-controlled clinical trials in the INDANA database. The main outcome was the SBP fall (DSBP) between randomization and first follow-up visit. Multiple linear regression analyses were used to evaluate the relationship between DSBP, treatment, baseline characteristics of patients, and interactions between these covariates and treatment. Significance level of p<0.10 was used for all analyses. The average DSBP were 10, 8, 5 mmHg with diuretics, BB, and CCB classes respectively. Baseline SBP was significantly correlated to DSBP whatever the drug class. Age and baseline diastolic blood pressure were significantly correlated to DSBP for diuretics and BB, but not for CCB. With BB, height was positively correlated to DSBP, while smoking status was negatively correlated to DSBP. Some individual characteristics explain a significant part of blood pressure reduction with drugs. These results will be integrated in algorithms to predict clinical benefit from these drugs.

Interactions between the adducin 2gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

BackgroundAs part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA) recruited 575 sibships (n = 1583 individuals) from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs) typed in 7 positional candidate genes, including adducin 2 (ADD2).MethodTo investigate whether blood pressure (BP) levels in these hypertensives (n = 1133) were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup). These methods greatly reduced the chance of false positive findings.ResultsEight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value < 0.05). Moreover, we also identified SNPs associated with gene-by-drug interactions on systolic BP in drug-treated hypertensives. The TT genotype at SNP rs1541582 was associated with an average systolic BP of 133 mmHg in the beta-blocker subgroup and 148 mmHg in the diuretic subgroup after adjusting for overall mean differences among drug classes.ConclusionOur findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.

Factors Influencing Blood Pressure Response to Trandolapril Add-On Therapy in Patients Taking Verapamil SR (from the International Verapamil SR/Trandolapril [INVEST] Study)

Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A-->C) in the angiotensin II type 1 receptor gene (AGTR1) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by -9.1 +/- 17.3 (SD) and -4.1 +/- 10.1 mm Hg, respectively. The percentage of patients with BP under control (<140/90 mm Hg) increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas the decrease in systolic BP was more pronounced in younger patients, the opposite was observed for diastolic BP decrease. Diastolic BP response was also significantly associated with race. Specifically, the adjusted diastolic BP decrease was significantly smaller in Hispanics and blacks than whites (p = 0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in systolic BP and an increase in BP control similar to the other ethnic groups. There was no genetic association between AGTR1 1166A-->C genotype and BP response. In conclusion, trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.

Gene markers and antihypertensive therapy

Increasingly, detailed characterization of human molecular genetic variation will facilitate the use of genetic information in preventing, diagnosing, and treating common diseases. One promising application is the identification of genetic variants influencing responses to drugs used to lower blood pressure (BP) and prevent target-organ complications of hypertension. This update on gene markers to guide antihypertensive therapy highlights polymorphisms recently reported to predict interindividual differences in response to antihypertensive medications. However, single-site variation in most genes makes only a small contribution to differences in BP response, and, after all known genetic and environmental predictors have been considered, most variation in responses still remains unexplained. Advancing beyond our current "trial-and-error" approach to selecting drug therapy in individual patients will undoubtedly require whole-genome approaches to discover additional, novel genetic pathways influencing drug response. In addition, larger samples will be required to more fully characterize genetic variation within candidate genes and to consider the joint effects of gene-gene and gene-environment interactions. Eventually, knowledge of genetic variants that influence BP responses may allow more individualized tailoring of therapy to optimally reduce BP and target-organ damage.

Blood Pressure Response to “Super-Slow” vs Traditional Resistance Exercise

1422 Super-slow(SLOW) resistance exercise has been touted as a more effective means to increase muscular strength compared to traditional (TRAD) resistance exercise, but health risks associated with blood pressure (BP) elevation during heavy weight lifting have been reported. Determining the extent to which BP is perturbed by different resistance exercise protocols could ameliorate risks. PURPOSE: To compare the baseline (following 5 min seated rest) and post exercise (15 sec, 15, 30, 45 and 60 min) BP response to SLOW, TRAD, and control (CON) resistance exercise. METHODS: Participants (11 females; 7 males; mean age 25.2 yr ± 7.6 SD; range 18–45), with no history of SLOW resistance training, and resting BP < 135/85, were randomized into a SLOW (10 sec concentric, 4 sec eccentric; 1 set of 6–8 reps, 50% 1RM), TRAD (2 sec concentric, 1 sec pause, 4 sec eccentric; 3 sets of 10–12 reps, 70% 1RM) or CON (2 sec concentric, 1 sec pause, 4 sec eccentric; 1 set of 12 reps, 70% 1RM) resistance protocol for the first trial. Other protocols were completed in random order at least one wk apart at the same time of day. A random zero sphygmomanometer was used for all BP measurements to decrease reader bias. Resistance exercises included the leg press, chest press, leg curl, lat pull-down, leg extension, and seated row. Upper and lower body stations were alternated with a 60-sec rest period between exercises and sets. Data were analyzed by a 2 × 3 (gender × protocol) repeated (time) measures ANOVA. Post hoc t-tests were used to further examine significant differences. RESULTS: Baseline BP was similar between genders and protocols. A main effect of protocol demonstrated that systolic and diastolic BP were higher in response to SLOW compared to TRAD and CON. A significant time effect was observed for systolic (p< 0.01) and diastolic (p < 0.01) BP. Baseline systolic BP (111.0 ± 8.5) was less (p < 0.01) than at 15 sec (127.0 ± 11.2) but greater (p < 0.05) than all other time points. Similarly, baseline diastolic BP (72.2 ± 6.3) was less (p < 0.01) than at 15 sec (79.2 ± 7.0), but did not differ (p > 0.05) from other time points. A main effect of gender demonstrated that BP was lower for females (p < 0.05) than males regardless of protocol. However, a gender by protocol interaction demonstrated that while the systolic BP in the females did not differ by protocol, in the males the BP was higher in response to the SLOW and TRAD protocol vs the control. CONCLUSION: Repetition speed may influence BP response to resistance exercise in males more so than females