FURIN variant associations with postexercise hypotension are intensity and race dependent.

FURIN is a proprotein convertase subtilisin/kexin enzyme important in pro-renin receptor processing, and FURIN (furin, paired basic amino acid cleaving enzyme) variants are involved in multiple aspects of blood pressure (BP) regulation. Therefore, we examined associations among FURIN variants and the immediate blood pressure (BP) response to bouts of aerobic exercise, termed postexercise hypotension (PEH). Obese (30.9 ± 3.6 kg  m-2 ) Black- (n = 14) and White- (n = 9) adults 42.0 ± 9.8 year with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous (VIGOROUS) and moderate (MODERATE) intensity cycling and control. Subjects were then attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. FURIN genotypes were coded as the number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing corrected P-values under time-adjusted linear models for 19 hourly BP measurements. After VIGOROUS over 19 h, as FURIN #MA increased in rs12917264 (P = 2.4E-04) and rs75493298 (P = 6.4E-04), systolic BP (SBP) decreased 30.4-33.7 mmHg; and in rs12917264 (P = 1.6E-03) and rs75493298 (P = 9.7E-05), diastolic BP (DBP) decreased 17.6-20.3 mmHg among Blacks only. In addition, after MODERATE over 19 h in FURIN rs74037507 (P = 8.0E-04), as #MA increased, SBP increased 20.8 mmHg among Blacks only. Whereas, after MODERATE over the awake hours in FURIN rs1573644 (P = 6.2E-04), as #MA increased, DBP decreased 12.5 mmHg among Whites only. FURIN appears to exhibit intensity and race-dependent associations with PEH that merit further exploration among a larger, ethnically diverse sample of adults with hypertension.

The Gly16 Allele of the Gly16Arg Single-Nucleotide Polymorphism in the ß2-Adrenergic Receptor Gene Augments Perioperative Use of Vasopressors: A Retrospective Cohort Study.

BACKGROUND: Arterial hypotension is frequent in patients undergoing anesthesia and may aggravate the outcome. Common genetic variations may influence the cardiovascular response to anesthesia. In this retrospective cohort study, we tested whether variation in the gene encoding the ß2-adrenergic receptor (ADRB2) influences perioperative arterial blood pressure and consequently the use of vasopressors. METHODS: Five hundred seventy-one Danish Caucasians undergoing neurosurgery were genotyped for 5 marker single-nucleotide polymorphisms (SNPs) within ADRB2 (Gly16Arg, Gln27Glu, Thr164Ile, Arg175Arg, and Gly351Gly). A pairwise tagging principle was used to identify ADRB2 haplotypes. Mean arterial blood pressure (MAP) was recorded in the supine awake state and, together with administration of vasopressors (ephedrine and/or phenylephrine), for 30 minutes after induction of general anesthesia (sevoflurane/remifentanil or propofol/remifentanil). RESULTS: Four hundred thirteen (72%) patients received ephedrine and/or phenylephrine. Only baseline MAP (P < 0.001) and the Arg175Arg SNP (P = 0.01) were associated with nadir perioperative MAP. The Gly16Arg SNP but no other SNPs showed a trend toward an association with the amount of vasopressors used during anesthesia with Arg16 homozygotes receiving less ephedrine equivalents. The Arg16-Gln27-Thr164-Arg175-Gly351 haplotype was associated with approximately 13% lower vasopressor requirements than the most common Gly16-Glu27-Thr164-Arg175-Gly351 haplotype (P = 0.01). CONCLUSIONS: Gly16 carriers received larger amounts of vasopressor compared with Arg16 homozygotes. This corresponds to previous studies demonstrating that the Gly16 allele in ADRB2 is associated with vasodilation and high cardiac output.

Blood pressure and stroke in heart failure in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND AND PURPOSE: The prevalence of stroke is increased in individuals with heart failure (HF). The stroke mechanism in HF may be cardiogenic embolism or cerebral hypoperfusion. Stroke risk increases with decreasing ejection fraction and low cardiac output is associated with hypotension and poor survival. We examine the relationship among blood pressure level, history of stroke/transient ischemic attack (TIA), and HF. METHODS: We compared the prevalence of self-reported history of stroke or TIA in the REasons for Geographic And Racial Differences in Stroke (REGARDS) participants with HF (as defined by current digoxin use) and without HF. We excluded participants with atrial fibrillation or missing data. We examined the relationship between HF and history of stroke/TIA within tertiles of systolic blood pressure (SBP) adjusting for patient demographic and health characteristics. RESULTS: Prevalent stroke/TIA were reported by 66 (26.3%) of 251 participants with and 1805 (8.5%) of 21 202 participants without HF (P<0.0001). Within each tertile of SBP, the unadjusted OR (95% CI) for prior stroke/TIA among those with HF compared with those without HF (the reference group) was, 4.0 (2.8 to 5.8) for SBP <119.5 mm Hg, 2.7 (1.8 to 3.9) for SBP >or=119.5 but <131.5 mm Hg, and 2.3 (1.6 to 3.2) for SBP >or=131.5 mm Hg. After adjustment, the relationship between prior stroke/TIA and HF remained significant only within the lowest tertile of SBP (<119.5 mm Hg; 3.0; 1.5 to 6.1). CONCLUSIONS: The odds of prevalent self-reported stroke/TIA are increased in participants with HF and most markedly increased in participants with low SBP. Longitudinal data are needed to determine whether this reflects stroke/TIA secondary to thromboembolism from poor cardiac function or secondary to cerebral hypoperfusion.

Invasive group A streptococcal disease: race, hypotension, and immunogenetics.

OBJECTIVE: To determine if there was an association between race and the incidence of hypotension among patients hospitalized for invasive group A streptococcal disease (IGASD). DESIGN: Data were obtained from a retrospective cohort study of IGASD patients. The subjects were hospitalized throughout Florida for IGASD between 1996 and 2000 (N=151). The exposure variable for the current study was race (African Americans, Caucasians). The binary outcome was the presence of hypotension within 48 hours of hospital admission. A sensitivity analysis was performed to determine if a particular human leukocyte antigen (HLA) class II haplotype (DRB1*1501/DQB1*0602) confounded the association between race and the risk of hypotension. IGASD patients possessing this haplotype are less likely to experience hypotension with multiple organ failure. RESULTS: We found that Caucasians had three times the odds of developing hypotension than African Americans (adjusted odds ratio=3.02, 95% confidence interval: 1.10-8.29, P=.03). The sensitivity analysis revealed that the HLA class II haplotype DRB1*1501/DQB1*0602 was most likely not a confounder. CONCLUSIONS: Caucasians were significantly more likely than African Americans to develop the adverse outcome of hypotension within 48 hours of being hospitalized for IGASD. This excess risk is most likely not due to a particular host genetic factor, the HLA class II haplotype DRB1*1501/DQB1*0602.

Postexercise hypotension differs between white and black women.

BACKGROUND: Because data are lacking, we examined the acute effect of exercise on ambulatory blood pressure (BP) in premenopausal white women (n = 18) and black women (n = 15) with normal (n = 21) and high (n = 12) BP. METHODS: Women performed 40 minutes of control and moderate-intensity exercise. BP and hormones were measured before, during, and after the control and exercise periods. By means of RMANCOVA (repeated measures analysis of covarience), we tested whether BP and hormones differed with time and between ethnic, BP, and experimental groups. Multiple regression analysis was used to examine hormonal mediators of the postexercise BP response. RESULTS: Among white women with hypertension, average daytime systolic (S) and diastolic (D) BP decreased 11.0 +/- 3.3 mm Hg (-2.9, -19.1; P =.017) and 8.2 +/- 2.8 mm Hg (-1.2, -13.9; P =.000), from 142.6 +/- 5.8 mm Hg and 96.1 +/- 2.8 mm Hg, respectively, after exercise. Among black women with high BP, mean daytime SBP rose 12.5 +/- 5.2 mm Hg (-2.0, 27.1; P =.000) after exercise, from 121.8 +/- 6.1 mm Hg, whereas DBP was similar before and after exercise (81.4 +/- 4.3 mm Hg and 82.8 +/- 4.7 mm Hg, respectively). In white women without hypertension, daytime SBP and DBP were similar before and after exercise. In black women without hypertension, mean daytime SBP increased 6.3 +/- 2.6 mm Hg (0.4, 12.1; P =.000) after exercise from 103.6 +/- 1.4 mm Hg, and DBP did not change. In black women, hypertension (P = 0.000) and exercise-mediated insulin decreases (P =.005) explained 85.6% of the postexercise SBP response (P =.000). In white women, hypertension (P =.003) and baseline plasma renin (P =.049) accounted for 53.3% of the postexercise SBP response (P =.001). Exercise acutely reduced daytime BP in white women, but not in black women with high BP. CONCLUSION: Endurance exercise may adversely affect the BP of black women.

The effect of race and sleep-disordered breathing on nocturnal BP "dipping": analysis in an older population.

STUDY OBJECTIVES: BP normally drops (or "dips") by approximately 10% at nighttime; however, in a number of illnesses there is an increased amount of "nondipping" of nocturnal BP. This study examined whether nondipping in older African Americans and older white subjects is related to the presence of sleep-disordered breathing (SDB) and hypertension. DESIGN: Prospective study with a convenience sample. SETTING: All data were collected in the subjects' homes. PARTICIPANTS: Seventy self-defined African Americans with complaints of snoring or excessive daytime sleepiness, and 70 age-matched and gender-matched white subjects. MEASUREMENTS AND RESULTS: Sleep was recorded for 2 nights, with 1 night of oximetry. BP was recorded on a separate 24-h period. African Americans had higher dipping ratios than white subjects even after accounting for covariates such as respiratory disturbance index (RDI), oxygen desaturation index (ODI), body mass index, and average 24-h mean arterial pressure (p = 0.025). Higher values of RDI (R(2) = 0.0686, p = 0.021) and ODI (R(2) = 0.042, p < 0.03) were correlated with higher dipping ratios in both African Americans and white subjects. However, there was a three-way interaction such that higher RDIs were correlated primarily with nondipping in African Americans receiving antihypertensive medication (R(2) = 0.0373, p = 0.022). CONCLUSIONS: These results demonstrated that African Americans tend to be "nondippers," while white subjects tended to be "dippers." This nondipping was not a result of weight, gender, or of having SDB. The analyses also confirmed that, in both races, the dipping ratio was greatest in those with SDB and hypertension. The third hypothesis, that RDI would be greatest in the nondipping hypertensive subjects, was true only for the African Americans.

Relationship between low blood pressure and depressive symptomatology in older people.

OBJECTIVES: To determine if low blood pressure is associated with a definable constellation of somatic and psychological symptoms in older persons. DESIGN: A population-based study. SETTING: In-home interviews in five southwestern states. PARTICIPANTS: A total of 2723 Mexican Americans aged 65 or older not living in institutions. MEASURES: Blood pressure, Center for Epidemiologic Studies Depression Scale (CES-D), global self-rating of health, and self-esteem. RESULTS: Bivariate analyses indicate a significant relationship between low blood pressure and increased depressive symptomatology; for example, systolic hypotensive subjects scored a CES-D mean of 12.07 +/- .67 compared to 8.99 +/- .95 for normotensives (P < .01). Regression analyses supported these findings when controlling for confounders such as gender, age, and use of antihypertensive medications. Subjects with low blood pressure also scored lower on self-esteem and global self-reported health and reported more days waking up feeling tired. CONCLUSIONS: These data support the existence of a relationship between low blood pressure and higher levels of depressive symptomatology as well as a constellation of somatic and psychosocial symptoms.

Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene.

PURPOSE: The angiotensinogen gene (AGT), which encodes the precursor of the vasoactive hormone angiotensin II, has been reported to be associated with hypertension in Caucasian and Japanese populations. We examined the relationship between two common molecular variants of AGT, T174M and M235T and blood pressure in two cohorts from the Anqing region of China. Cohort I (N = 794) consisted of families ascertained by either hypertensive or hypotensive siblings; and Cohort II (N = 761) represented a collection of randomly selected families. METHODS: Blood pressure was measured according to standard protocols, and information on age, sex, body mass index, alcohol consumption, and cigarette smoking was collected by trained interviewers using standardized questionnaires. The association of AGT genotypes and blood pressure was examined in multivariate linear regression models, with adjustment for potential intrafamilial correlations. The respective T and M allele frequencies for T174M were 0.93 and 0.07, and 0.80 and 0.20 for M235T among the parents for randomly selected families. All the analyses were conducted after exclusion of individuals currently under antihypertensive medication. RESULTS: In the pooled analysis of the two cohorts, neither the T174M nor the M235T polymorphism was significantly associated with variations of blood pressure assuming a recessive (T174M: p = 0.73 and 0.61; M235T: p = 0.99 and 0.24; for SBP and DBP), dominant (T174M: p = 0.54 and 0.72; M235T: p = 0.79 and 0.12; for SBP and DBP), or additive (T174M: p = 0.52 and 0.67, M235T: p = 0.91 and 0.11; for SBP and DBP) model. Likewise, no statistically significant association was detected when the two cohorts were analyzed separately. The logistic regression analysis of hypertension also failed to reveal any association with these markers. CONCLUSIONS: In summary, our analyses suggest that the molecular variants of AGT may not be associated with variations of blood pressure in this rural Chinese population.