Diastolic Blood Pressure Response Research Articles

Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression

Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. Methods: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. Results: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (β = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (β = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (β = 20.47, p = 0.032). Conclusions: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension.

Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults.

Corin, a transmembrane serine protease that can cleave pro‐atrial natriuretic peptide (Pro‐ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt‐Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7‐day low salt diet (3 g/day) and a 7‐day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low‐salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low‐salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high‐salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow‐up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene‐based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8‐year follow‐up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.

Aging exaggerates blood pressure response to ischemic rhythmic handgrip exercise in humans.

Ischemic skeletal muscle conditions are known to augment exercise‐induced increases in blood pressure (BP). Aging is also a factor that enhances the pressor response to exercise. However, the effects of aging on the BP response to ischemic exercise remain unclear. We, therefore, tested the hypothesis that aging enhances the BP response to rhythmic handgrip (RHG) exercise during postexercise muscle ischemia (PEMI). We divided the normotensive participants without cardiovascular diseases into three age groups: young (n = 26; age, 18–28 years), middle‐aged (n = 23; age, 35–59 years), and older adults (n = 23; age, 60–80 years). The participants performed RHG exercise with minimal effort for 1 min after rest with and without PEMI, which was induced by inflating a cuff on the upper arm just before the isometric handgrip exercise ended; the intensity was 30% of maximal voluntary contraction force. Under PEMI, the increase in diastolic BP (DBP) from rest to RHG exercise in the older adult group (Δ13 ± 2 mmHg) was significantly higher than that in the young (Δ5 ± 2 mmHg) and middle‐aged groups (Δ6 ± 1 mmHg), despite there being no significant difference between the groups in the DBP response from rest to RHG exercise without PEMI. Importantly, based on multiple regression analysis, age remained a significant independent determinant of both the SBP and DBP responses to RHG exercise during PEMI (p < 0.01). These findings indicate that aging enhances the pressor response to ischemic rhythmic exercise.

Efeito agudo do Mat Pilates sobre a variabilidade da pressão arterial ambulatorial em mulheres após a menopausa

Introdução: Após a menopausa mulheres tem maior risco de desenvolver doenças cardiovasculares. A prática de exercício físico é um dos tratamentos para e redução da incidência dessas doenças, e o método Pilates consiste em um programa completo de condicionamento físico. Objetivos: Verificar as respostas da Monitorização Ambulatorial da Pressão Arterial (MAPA) e da Variabilidade da Pressão Arterial após uma única sessão de Mat Pilates em mulheres após a menopausa não obesas. Métodos: Este é um estudo cruzado randomizado com 15 mulheres pós-menopáusicas normotensas, que participaram de uma única sessão de Mat Pilates e de uma sessão de controle. A sessão de Pilates durou 50 minutos, com 5 minutos de aquecimento. Em cada exercício, houve 1 série de 10 repetições com 45 segundos de descanso entre as séries. A sessão controle teve a mesma duração, mas as voluntárias permaneciam sentadas. A MAPA foi avaliada durante 24 horas após a intervenção. Estatística: Utilizou-se ANOVA de dois fatores com post hoc de Newman-Keuls para análise das variáveis da MAPA e teste t de Student para análise da variabilidade de pressão arterial. Resultados: Não houve diferença significativa (p &lt;0,05) nas respostas da pressão arterial sistólica e diastólica durante 24h, vigília e sono ou em sua variabilidade entre as sessões de Pilates e Controle. Conclusão: O Mat Pilates não reduziu os valores pressóricos da MAPA ou sua variabilidade em mulheres após a menopausa não obesas.

Effects of repeated exposures to experimental cold pain stimulus on pain perception in healthy young Indian men

BackgroundThe influence of repeated exposures to cold pain stimulus, a surrogate of clinical pain, has remained largely unexplored. The study was planned to test the effect of repeated exposures to cold pain through cold pressor task on pain sensitivity and vascular reactivity. MethodsSingle-group experimental study. Thirty-seven healthy male volunteers (18–25 years) were exposed to cold pressor tasks for seven consecutive days and on the 14th day on the nondominant hand. The same was repeated on dominant hand on first and seventh days; 31 completed the protocol. ResultsPain threshold and tolerance in the nondominant hand increased from day 1 to day 7 (p < 0.001) and were positively correlated on day 1 (ρ=0.45, p = 0.011) and day 7 (ρ=0.38, p = 0.036). Diastolic blood pressure response was found to increase by day 7 (p < 0.0024) and positively correlated with tolerance. On the dominant hand, the threshold reduced from day 1 to day 7, while tolerance increased. Both threshold and tolerance remained lower than that of nondominant hand. Day 14 values of threshold and tolerance were in between day 1 and day 7 values but not significantly different from both. ConclusionHabituation in pain threshold and tolerance was observed on repeated exposure to cold pain, which was not significantly retained till the 14th day. The same was not observed with subjective feeling of pain perception. The increased diastolic blood pressure response is suggestive of peripheral vasoconstriction. Increased tolerance in the dominant hand by day 7 demonstrates a systemic effect in habituation.

Unpredictable Chronic Mild Stress-Induced Depressive-Like Behaviors in Spontaneously Hypertensive Rats

Objective: The objective is to explore whether hypertension influences unpredictable chronic mild stress (UCMS)-induced depressive-like behaviors and the potential therapeutic effect of Guan-Xin-Shu-Tong capsules (GXST) in controlling hypertension and depressive-like behaviors. Materials and Methods: Fifteen spontaneously hypertensive rats (SHR) and 15 wistar rats were divided into three groups respectively (n = 5, in each group), including control, UCMS, and UCMS + GXST groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded at baseline and at the end of the experiment. Rats were subjected to seven kinds of UCMS over 4 weeks. GXST treatments were administrated (2.8 g/kg) by intragastric gavage once a day over 4 consecutive weeks during UCMS treatment. Sucrose-preference and open-field tests were used to detect depressive-like behaviors. Results: SHR exposed to 4-week UCMS treatment had lower HR when compared with control and UCMS + GXST groups (P &lt; 0.05); Wister rats receiving UCMS or UCMS + GXST had lower SBP (P &lt; 0.05), lower DBP (P &lt; 0.05) and lower MAP (P &lt; 0.05) than controls. Compared with the controls, UCMS reduced the sucrose preference of Wistar rats, UCMS and UCMS + GXST decreased both grid-crossings and the number of upright postures measured in Wistar rats (P &lt; 0.05). SHR showed lower sucrose consumption, less sucrose preference, and fewer grid-crossings after UCMS than control SHR. However, the lower incidence of upright postures in SHR was prevented by GXST treatment (P &lt; 0.05). Linear correlation showed that grid-crossings or upright postures were negatively related to the values of SBP, DBP, or MAP, presenting the positive relationship between depressive-like behaviors and SBP, DBP, or MAP reduction in Wistar rats; there was a negative correlation between grid-crossings and DBP responses, and MAP responses in SHR, and a positive correlation between depressive-like behaviors and DBP and MAP response elevation in SHR. Conclusions: UCMS-induced depressive-like behaviors in Wistar and SHR, accompanied by a blood pressure decrease in Wistar rats but not in SHR. While GXST exhibited effective relief of depressive-like behaviors in SHR without influencing their blood pressure.

Differences in Blood Pressure and Workload Intensity During Arm and Leg Ergometry at Submaximal Target Heart Rates in College-Aged Individuals

Purpose: Blood pressure (BP) during arm (AE) and leg ergometry (LE) have traditionally been compared at submaximal intensities of the peak oxygen uptake, which is often challenging to interpret in clinical practice. The purpose of this investigation was to evaluate the relationship of the heart rate with systolic blood pressure (SBP), diastolic blood pressure (DBP), and workload (WL) during AE and LE exercise. Methods: A prospective, observational, cross-sectional design with 35 healthy subjects compared BP and WL during AE and LE at specific submaximal target heart rates (HRs) of 110, 120, 130, 140, and 150 beats per minute. A linear mixed model tested for differences in SBP, DBP, and WL between AE and LE. Results: There was a larger increase in SBP {0.55 mm Hg (95% CI [0.38, 0.73])} per heart beat during LE. There was a larger increase in WL {0.62 watts (95% CI [0.38, 0.85])} and WL relative to body mass {0.01 watts/kg (95% CI [0.006, 0.011])} per heart beat during LE. Statistical models were developed that estimated SBP, DBP, and WL based on the submaximal heart rate. Conclusion: The findings from this investigation informs physical therapists that lower SBP, higher DBP, and lower WL is achieved at any given submaximal HR during AE compared with LE. Furthermore, prediction equations derived from the statistical models can be used to compare actual against predicted SBP and DBP responses to determine tolerance to exercise. Finally, differences in WL per beat increase in HR are valuable in dosing exercise on the AE or LE.

Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.

We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n=9,195; calcium channel blockers (CCBs), n=10,511; thiazide/thiazide-like diuretics, n=3,516; ACE-inhibitors/ARBs, n=2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n=21,267), blood pressure (BP) response in independent ICAPS studies (n=1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n=5,115). One signal reached genome-wide significance in the β-blocker-SNP interaction analysis (rs139945292, Interaction P=1.56×10-8 ). rs139945292 was validated through BP response to β-blockers, with the T-allele associated with less BP reduction (systolic BP response P=6×10-4 , Beta=3.09, diastolic BP response P=5×10-3 , Beta=1.53). The T-allele was also associated with increased adverse cardiovascular risk within the β-blocker treated patients' subgroup (P=2.35×10-4 , odds ratio=1.57, 95% confidence interval=1.23-1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β-blocker treated patients. Further investigation into this region is warranted.

Exploring relationships between inspiratory muscle strength and functional capacity in childhood cancer survivors: a pilot study

Childhood cancer survivors (CCS) experience short- and long-term side effects from cancer treatment that often impair functional capacity. Inspiratory muscle weakness is a potential mechanism for reduced functional capacity. The objective of this pilot study was to examine the relationship between inspiratory muscle strength and functional capacity in 10 CCS. Inspiratory muscle strength was measured by maximal inspiratory pressure (MIP) while functional capacity was measured by the two-minute walk test (2MWT), the physiological cost index and hemodynamic response to exercise according to changes in heart rate, blood pressure and rate-pressure product (RPP). Overall, MIP and 2MWT distance were below predicted values. Hemodynamic responses to the 2MWT were consistent with little variation, except for elevated diastolic blood pressure (DBP) response. MIP had significant relationships with resting DBP (Spearman’s rank correlation coefficient [rs ] = −0.70; p = 0.03) and DBP response (rs = 0.72; p = 0.02). Time since completion of cancer treatment had a significant positive relationship with RPP response (rs = 0.67; p = 0.03). Inspiratory muscle weakness in childhood cancer could be an indicator of skeletal muscle dysfunction and should be considered when symptoms of dyspnea or poor functional capacity arise. Inspiratory muscle strength was found to be related to changes in blood pressure in CCS. Future studies should further investigate these relationships and the impact of inspiratory muscle training on hemodynamics and functional capacity in CCS.

Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency?

Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r = -0.42; P < 0.01) and the sympathetic transduction slope (r = -0.66; P < 0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r = 0.04; P = 0.78), but positively correlated in females (r = 0.44; P < 0.01) and with the sympathetic transduction slope in all participants (r = 0.42; P < 0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In subanalysis of males (38 ± 10 vs. 14 ± 4 bursts/min) and females (28 ± 5 vs. 12 ± 4 bursts/min) with high versus low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P < 0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high versus low MSNA (all P > 0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.

Sudomotor and cardiovascular autonomic function in de novo Parkinson's disease assessed by sudoscan and cardiovascular reflexes

ObjectiveThe prevalence of autonomic involvement in early stage of Parkinson ‘s disease (PD) is still debated. Aim of this study is to assess the autonomic functions in de novo PD patients (dnPD) in comparison with PD patients on therapy (PDot) and healthy controls (HC). MethodsTwenty-eight dnPD and 24 PDot, to whom Unified Parkinson's Rating Scale (UPDRS) was administered, and 23 HC underwent electrochemical skin conductance (ESC) measured with sudoscan, cardiovascular reflexes (head-up tilt test HUTT, Valsalva maneuver, deep breathing, hand grip, and cold face),and Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT) questionnaire. ResultsThe mean SCOPA-AUT total score was significantly higher in dnPD group compared with HC group (p < 0.001) and significantly lower than PDot (p = 0.004). No significant difference of ESC mean values were found between dnPD and HC group. DnPD had a significantly lower diastolic blood pressure (BP) response at handgrip test (p = 0.005) compared with HC. Hands and feet ESC significantly negatively correlated with disease duration (p = 0.014; p = 0.025) and feet ESC significantly negatively correlated with UPDRS III (p = 0.039). Systolic and diastolic BP responses at 3rd minute of HUTT correlated significantly negatively with disease duration (p < 0.001; p = 0.003) and with UPDRSIII (p = 0.001; p < 0.001). BP response to Valsalva maneuver negatively correlated with UPDRSIII (p = 0.006). ConclusionAlthough dnPD patients complain of thermoregulatory symptoms, we found no alteration in the sudomotor function investigated with sudoscan. Furthermore, a deficit of the sympathetic vasoconstrictive response to the isometric exercise was detected, suggesting an early involvement of the autonomic cardiovascular components in dnPD.

Changes in vitality in response to acute stress: an investigation of the role of anxiety and physiological reactivity

ABSTRACT Background: Feeling alive and invigorated, or vitality, is examined within the framework of a stress paradigm. The current study investigated whether endocrine and cardiovascular responses to acute psychological stress predict declines in vitality. Methods: A sample of 90 undergraduate students completed an in-lab stressor. We measured anxiety, state vitality, cortisol levels, heart rate, and blood pressure before the task, and measured changes in state vitality, cortisol, heart rate, and blood pressure in response to the stressor. We investigated whether pre-task anxiety predicted changes in state vitality, and whether such changes were explained by physiological responses. Results: Results indicate that cognitive and somatic anxiety preceding a stressor predict changes in vitality, which is mediated by the magnitude of diastolic (95% CI [0.017, 0.517]; [0.006, 0.454]) and systolic (95% CI [0.038, 0.705]) blood pressure responses to the task. Cortisol reactivity was associated with somatic anxiety (F(6, 83) = 3.34, p < .01, β = 0.401) but was not related to changes in vitality. Conclusions: Together, these results contribute to the understanding of how physiological reactivity to a stressor can deplete vitality.

Associations of adverse childhood experiences with stress physiology and insulin resistance in adolescents at risk for adult obesity

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0-17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above-average body mass index (BMI; kg/m2 ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m2 ). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty-one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p-values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day-to-day variations in adolescents' stress physiology and glucose homeostasis.

GENOME-WIDE ASSOCIATION STUDY FOR PHARMACOGENETIC RESPONSE OF BLOOD PRESURE TO BETA BLOCKER AND CALCIUM CHANNEL BLOCKER DRUGS

Objective: There is substantial inter-individual variability in blood pressure (BP) responses to anti-hypertensive drugs and it is hypothesised that there could be genetic influences. One goal of pharmacogenetics is to aid in treatment selection. However very few variants have been identified. After the success of genome-wide association studies (GWAS) for BP, it is hoped GWAS could also reveal genes associated with BP treatment response. Design and method: A discovery analysis was performed including participants from ASCOT and NORDIL studies. Six different analyses were performed for systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) responses to monotherapy beta blockers (BBs) and calcium channel blockers (CCBs). BP response was defined as post-treatment BP minus baseline BP. All analyses adjusted for age, sex, baseline BP and principal components. ASCOT analyses were also adjusted for dose and previous antihypertensive use, and excluded patients taking either BB/CCB drug at baseline, whereas NORDIL participants were previously untreated and subsequently treated on the same drug dose. Genotyped data was imputed to 1000 Genomes, testing ∼7million common variants. Results from ASCOT and NORDIL were meta-analysed, with total N = 2,556 for BBs and N = 3,369 for CCBs. Any variants reaching P &lt; 1 × 10-5 for SBP and DBP response to BBs were tested for replication in available ICAPS consortium data (N = 1,328). Results: Strong correlation between baseline BP and BP response shows patients with higher BP have greater BP reduction post-treatment. No variants reached genome-wide significance in any of the GWAS analyses, and none replicated in ICAPS data. Lookups of ∼1,000 published BP-associated variants were performed, but none reached Bonferroni significance level. Ongoing analyses are testing BP genetic risk scores for association with treatment response. Comparison of GWAS results shows correlation between SBP vs DBP response (r2 = 0.48) and SBP vs PP response (r2 = 0.76), but none between response to BBs vs CCBs. Conclusions: Despite being the largest GWAS of antihypertensive response, we found no significant associations, showing that larger studies are still required to increase power for discoveries. Model comparisons show different genes are likely to influence response to different antihypertensive drugs, with different genetic architecture.

HYPERTENSIVE PATIENTS WITH GREATER GENETIC RISK RESPOND LESS EFFECTIVELY TO TREATMENT AND ARE MORE LIKELY TO BE TREATMENT RESISTANT

Objective: Patients with resistant hypertension (RHTN) have increased cardiovascular disease risk. It is believed there may be genetic causes, although robust associations remain to be validated. Over 1,000 genetic loci have been discovered for BP from genome-wide association studies (GWAS), with application of genetic risk scores (GRS) enabling population risk stratification. However it is unknown whether genetic risk influences treatment response. We investigated whether BP associated loci: (i) are associated with RHTN; (ii) mediate the effect of antihypertensives on BP lowering response. Design and method: We analysed 6,266 patients of European ancestry with genetic data from ASCOT. BP-GRSs were constructed for systolic (SBP), diastolic BP (DBP) and pulse pressure (PP) using all available 1,167 pairwise-independent published BP-associated genetic variants, weighted by their effect estimates from our recent BP-GWAS in N∼750k individuals. We tested the BP-GRS for association with: (i) RHTN, adjusted for known non-genetic predictors: sex, age, BMI, diabetes, randomization treatment arm and left ventricular hypertrophy; (ii) BP response to monotherapy treatment, adjusted for sex, age, baseline-BP, dose and baseline antihypertensive use. All analyses adjusted for 10 principal components of ancestry. Results: Each BP-GRS is significantly associated with RHTN (P = 1.13 × 10-13, 1.96 × 10-5, 1.21 × 10-14 for SBP, DBP, PP) with increased genetic risk leading to increased odds of RHTN. Patients in the top 20% of SBP-GRS have 1.74 times greater odds of RHTN than the lowest 20% (P = 6.96 × 10-10). Additional adjustment for baseline-BP does not change conclusions. The association even remains significant (P = 5.11 × 10-4) with stronger effect (OR = 2.52) when restricted only to 1,037 patients untreated at baseline. The BP-GRS is also significantly associated with SBP and DBP response to amlodipine (N = 1,780): patients in the lowest 20% genetic risk group achieve better lowering response by 3.77mmHg mean difference between SBP pre and post treatment (P = 8.27 × 10-4). Conclusions: Our results confirm the hypothesis for a genetic contribution to RHTN, indicating RHTN patients are likely to be those with highest genetic risk of hypertension, which helps to explain the clinical challenge. We show that those with greater BP genetic risk respond less effectively to treatment and provide evidence that BP genes also influence treatment response.

Association of Blood Pressure and Heart Rate Responses to Submaximal Exercise With Incident Heart Failure: The Framingham Heart Study.

BackgroundExercise stress tests are conventionally performed to assess risk of coronary artery disease. Using the FHS (Framingham Heart Study) Offspring cohort, we related blood pressure (BP) and heart rate responses during and after submaximal exercise to the incidence of heart failure (HF).Methods and ResultsWe evaluated Framingham Offspring Study participants (n=2066; mean age, 58 years; 53% women) who completed 2 stages of an exercise test (Bruce protocol) at their seventh examination (1998–2002). We measured pulse pressure, systolic BP, diastolic BP, and heart rate responses during stage 2 exercise (2.5 mph at 12% grade). We calculated the changes in systolic BP, diastolic BP, and heart rate from stage 2 to recovery 3 minutes after exercise. We used Cox proportional hazards regression to relate each standardized exercise variable (during stage 2, and at 3 minutes of recovery) individually to HF incidence, adjusting for standard risk factors. On follow‐up (median, 16.8 years), 85 participants developed new‐onset HF. Higher exercise diastolic BP was associated with higher HF with reduced ejection fraction (ejection fraction <50%) risk (hazard ratio [HR] per SD increment, 1.26; 95% CI, 1.01–1.59). Lower stage 2 pulse pressure and rapid postexercise recovery of heart rate and systolic BP were associated with higher HF with reduced ejection fraction risk (HR per SD increment, 0.73 [95% CI, 0.57–0.94]; 0.52 [95% CI, 0.35–0.76]; and 0.63 [95% CI, 0.47–0.84], respectively). BP and heart rate responses to submaximal exercise were not associated with risk of HF with preserved ejection fraction (ejection fraction ≥50%).ConclusionsAccentuated diastolic BP during exercise with slower systolic BP and heart rate recovery after exercise are markers of HF with reduced ejection fraction risk.

Associations between cardiac troponin I and cardiovascular parameters after 12-week endurance training in young moderately trained amateur athletes

BackgroundPrevious studies were conducted only on elite athletes, and they investigate acute training responses of cardiac troponin I (CTnI). However, cardiac troponin was found to be elevated in young and...

The Effect of High Temperature on Cardiovascular Autonomic Function Tests in Steel Plant Furnace Worker

Background:The high temperature in the working environment could be one of the risk factors for cardiovascular diseases in steel plant workers. The excessive high temperature at the working place leads to altered autonomic activity and is related to more cardiovascular risk.Aims and Objectives:The effect of high temperature on cardiovascular autonomic function tests in steel plant furnace worker.Material and Method:This was a case-control study for which 50 steel plant furnace workers and 50 controls were selected. The cardiovascular sympathetic function status in worker and control were analyzed by three tests: (i) Blood pressure (BP) response to sustained isometric handgrip test, (ii) BP response to the cold pressor test, and (iii) BP response to standing from a supine position (orthostasis). Statistical analysis was done by using an independent t-test.Results:Diastolic BP (DBP) response to sustained isometric handgrip and systolic BP (SBP) and DBP response to the cold pressor test showed that the increase BP in workers were more than controls but the difference was not statistically significant (P > 0.05). SBP response to standing from the supine position showed statistically significant (P < 0.001) greater fall in steel plant workers.Conclusion:The sympathetic autonomic dysfunction was seen in steel furnace workers in response to environmental stressor–excessive heat.

Effects of a mindfulness-induction on subjective and physiological stress response in adolescents at-risk for adult obesity

BackgroundMindfulness-training may benefit stress response and stress-eating, yet few studies have experimentally tested these effects in adolescents. In this short communication, we report whether a brief mindfulness-induction affected acute stress response and stress-eating in adolescents at-risk for adult obesity. We explored disordered eating as a moderator. MethodTwenty-nine adolescents (age 14 ± 2 y) at-risk for adult obesity participated in a within-subjects, randomized crossover experiment. Following a 10-minute mindfulness or neutral-induction on different days in random order, the Trier Social Stress Test adapted for adolescents was administered, followed by an ad libitum lunch meal. Physiological stress response (heart rate, blood pressure) and subjective stress response (anxiety, mindlessness) were determined with area under the curve with respect to increase. Stress-eating was measured as test meal energy consumed. Global disordered-eating and binge-eating were assessed with the Eating Disorders Examination-Questionnaire. ResultsRelative to a neutral-induction, a mindfulness-induction reduced state anxiety response (p = .04). There were significant interactions of induction-type by global disordered-eating (p = .02) and binge-eating (p = .03), such that the mindfulness-induction most reduced anxiety response in adolescents with relatively lower global disordered-eating and those with no binge-eating. Induction-type also interacted with binge-eating in predicting diastolic blood pressure (p = .03). A mindfulness-induction, versus neutral-induction, most reduced diastolic blood pressure response in adolescents with binge-eating. ConclusionsBrief mindfulness-training may alter some aspects of acute stress response, with variations by disordered-eating. Future research should test alternative mindfulness induction-types (e.g., acceptance/self-compassion) to improve our understanding of how mindfulness-training may benefit adolescents at-risk for adult obesity.

Abstract 15986: Plasma Microrna Profiling Reveals Potential Biomarkers of Thiazide Response

Introduction: Thiazide diuretics (TZDs) are the second most frequently prescribed class of antihypertensives. But &lt;50% patients achieve goal blood pressure (BP) on TZD monotherapy, mostly because therapy is chosen overlooking the heterogeneity in patient responses. Circulating microRNAs (miRNAs) remain attractive as non-invasive biomarkers to predict drug response and tailor therapy for optimal outcomes. Hypothesis: Plasma miRNAs may play a role in TZD response; we aim to identify those associated with hydrochlorothiazide (HCTZ) response. Methods: We profiled 754 miRNAs in baseline (untreated) plasma samples of 36 uncomplicated hypertensive adults (18 Responders (R) and 18 Non-responders (NR) based on their diastolic BP (DBP) response to HCTZ therapy) from the Pharmacogenomic Evaluation of Antihypertensive Responses clinical trial, using the real-time qPCR based TaqMan OpenArray Human microRNA panel. We filtered out miRNAs with low amplification scores and Cq&gt;38 and samples with low miRNA expression. Combination of miR-223 and miR-19b (identified as most stably expressed miRNAs by NormFinder Software) was used to normalize expression across samples. We used MannWhitney U test to identify microRNAs differentially expressed between R and NR; linear and logistic regressions for associations of miRNA expression with BP response. FDA corrected p&lt;0.05 was used as significance threshold, unadjusted p&lt;0.05 as suggestive threshold. Results: Mean systolic BP (SBP)/DBP change in R was 14/10 mmHg and in NR 0/1 mmHg. We found 77 miRNAs to be consistently expressed across samples, of which 11 were upregulated and 14 downregulated with &gt;2-fold difference between R and NR. Though no miRNAs reached FDR p&lt;0.05, miR-376a (fold change(fc)= 10.1, p= 0.035) and miR-17 (fc= -0.45, p= 0.017) were differentially expressed between R and NR and their expression associated with DBP and SBP change, along with miR-10b, miR-24, miR-134 associated with SBP change at p&lt;0.05. Conclusions: In this first ever genome-wide miRNA study of antihypertensive drug response, we discovered circulating miRNAs associated with BP response to HCTZ. Future studies are planned to validate these findings in a larger cohort, across different race group and across different TZD.