Journal of the American Society of Hypertension - Articles in Press

Proposal of RAS-diuretic vs. RAS-calcium antagonist strategies in high-risk hypertension: insight from the 24-hour ambulatory blood pressure profile and central pressure - Corrected Proof

Kazuomi Kario — 2010-08-23

Abstract: I here propose an individualized renin angiotensin system (RAS) inhibitor-based combination therapy with calcium-channel blockers (CCBs) or with diuretics, based on the 24-hr ambulatory blood pressure (BP) profiles and central pressure in relation to the target organ damage in high-risk hypertensive patients. For high-risk patients with increased circulating volume, such as that caused by chronic kidney disease (CKD) or congestive heart failure (CHF), who are likely to exhibit a non-dipper/riser pattern of nocturnal BP fall, diuretics are recommended in combination with a RAS inhibitor to reduce nocturnal BP preferentially. For high-risk patients with arterial diseases such as cardiovascular disease and increased arterial stiffness, who are likely to exhibit exaggerated BP variability, such as morning BP surge and day-to-day BP variability, a CCB is recommended for use in combination with a RAS inhibitor to reduce BP variability and central BP. In particular, bedtime dosing of a RAS inhibitor targeting sleep-early morning activation of RAS may be particularly effective for cardiorenal protection.

The association between acculturation and hypertension in a multiethnic sample of US adults - Corrected Proof

Srinivas Teppala, Anoop Shankar, Alan Ducatman — 2010-08-23

Abstract: Previous studies analyzing acculturation and cardiovascular risk were restricted to individual race/ethnic groups and did not fully account for potential confounders. We examined the independent association between acculturation and hypertension in a contemporary multiethnic sample that included white, black, Latino, and Asian individuals. We examined 51,048 participants in the 2007 California Health Interview Survey who were >18 years, 59.5% of whom were women. The main exposure-of-interest was acculturation score, a summary measure of the additive effect of 4 variables (country of birth, parents’ country of birth, language at home, and duration of stay in the United States) ranged from 0 (least acculturation) to 4 (highest acculturation). We found that increased acculturation was associated with hypertension, independent of age, gender, race/ethnicity, education, smoking, alcohol, physical activity, body mass index, and diabetes. Compared with those with the lowest acculturation (score of 0), the multivariable odds ratio (95% confidence interval) of hypertension among those with the highest acculturation (score of 4) was 1.78 (1.50–2.11). This association between acculturation and hypertension was consistent in subgroup analyses by gender, education, smoking, alcohol intake, and body mass index. Increased Western acculturation was found to be positively associated with hypertension in a multiethnic sample, independent of confounders.

Central blood pressure measurements—an opportunity for efficacy and safety in drug development? - Corrected Proof

2010-08-23

Abstract: Over a century of experience with brachial blood pressure has produced a substantial amount of information on the role of blood pressure as a factor in heart disease, stroke and kidney failure. Successful interventions lowering blood pressure and reducing damage to vital organs testify further to the importance of this vital sign. In recent years attempts to probe deeper into the value of knowledge of blood pressure levels closer to the heart (central blood pressures) suggest that noninvasive measurement of central aortic blood pressure may improve further efforts directed at both understanding drug benefit and uncovering potential drug safety issues. This commentary is a summary of a one-day meeting with the FDA in which the role of central blood pressure measurements as an adjunct to drug efficacy and safety were addressed.

Level of blood pressure above goal and clinical inertia in a Medicaid population - Corrected Proof

2010-08-23

Abstract: Failure to adjust hypertension therapy despite elevated blood pressure (BP) levels is an important contributor to lack of BP control. One possible explanation is that small elevations above goal BP are not concerning to clinicians. BP levels farther above goal, however, should be more likely to prompt clinical action. We reviewed 1 year’s worth of primary care records of 3742 North Carolina Medicaid recipients 21 years and older with hypertension (a total of 15,516 office visits) to examine variations in hypertension management stratified by level of BP above goal and the association of BP level above goal with documented antihypertensive medication change. Among the 53% of patients not at goal BP, 42% were within 10/5 mm Hg of goal; 11% had a BP 40/20 mm Hg or higher above goal. Higher level of BP above goal was independently associated with antihypertensive medication change. Compared with visits at which BP was less than 10/5 mm Hg above goal, the adjusted odds of medication change were 7.9 (95% Confidence Interval 6.2–10.2) times greater at visits when patients’ BP was 40/20 mm Hg or higher above goal. However, even when BP was above goal at this level, treatment change occurred only 46% (95% Confidence Interval 40.2–51.8) of the time.

Endothelin-1 response to glucose and insulin among African Americans - Corrected Proof

Stephanie DeLoach, Yonghong Huan, Constantine Daskalakis, Bonita Falkner — 2010-08-23

Abstract: Endothelin-1 (ET-1) is implicated in the pathogenesis of hypertension. In vitro studies demonstrate that ET-1 is upregulated by insulin and glucose. The purpose of this study was to determine the effects of insulin and glucose on ET-1 levels in young adult African Americans, a population with a high burden of hypertension and diabetes. Plasma and urine ET-1 levels were measured before and after an oral glucose tolerance test (OGTT) and insulin clamp procedure in 288 participants. Subjects were classified according to glucose tolerance and blood pressure (BP) status. Plasma and urine ET-1 were not significantly different among the glucose tolerance groups. There was a trend toward increased plasma ET-1 among those with diabetes compared with impaired glucose tolerance and normal glucose tolerance; however, this was not statistically significant (P = .085). According to BP status, plasma ET-1 was highest among the high BP group compared with the normal BP group (P = .01). After glucose challenge, plasma ET-1 levels decreased and urine ET-1 increased in all three BP groups (P = .037). Our data show that plasma ET-1 is higher among young adult African Americans with hypertension compared with normotension. Urine ET-1 levels increased in response to glucose challenge, possibly indicating early renal injury.

From the Editor - Corrected Proof

Myron H. Weinberger — 2010-08-23

This issue of the Journal of the American Society of Hypertension features several intriguing and informative reports. The first article is a report by Dr. Townsend and colleagues of the initial meeting of the North American Artery Association held in Bethesda, MD, in April 2010. This meeting included investigators from academia and industry, medical device manufacturers, and members of the Food and Drug Administration interested in the issues involved in measurements of vascular dynamics and central as well as peripheral blood pressure. The article addresses several issues that arose during this meeting, including the possible role of central blood pressure measurements as a better predictor of cardiovascular outcomes in hypertension than the conventional brachial artery measures. The article reviews cardiovascular physiology with these differences in mind. It features descriptions of the available equipment for these measurements. A discussion of the emerging evidence for the importance of central blood pressure estimation from several recent trials provides further stimulus for future investigation.

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension - Corrected Proof

2010-08-13

Abstract: The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was −1.6 mm Hg (−4.2, 1.1), −1.1 mm Hg (−3.9, 1.6), and −4.9 (−7.5, −2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (−6.7 mm Hg [−10.5, −2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.