Pharmacogenomic Genome-Wide Association Study of Blood Pressure Response to β-Blockers in Blacks (p 556)
Hypertension is the most important risk factor for global cardiovascular disease burden, and it is particularly problematic in blacks who have higher prevalence of hypertension when compared with other race/ethnic groups. Overall, β-blockers are often viewed as a suboptimal antihypertensive drug class in blacks, despite recognition that blood pressure (BP) response to any antihypertensive class is characterized by large interindividual variation. We showed that 20% to 30% of black participants with uncomplicated hypertension responded well to β-blocker treatment. Our findings suggest that β-blocker therapy can be an effective antihypertensive drug class for a portion of blacks. However, given that β-blockers would be optimal in a minority of blacks, identifying those patients a priori would be instrumental in optimal and precise antihypertensive selection. In this first pharmacogenomics genome-wide meta-analysis of BP response to β-blockers in blacks, we identified 2 variants that were validated across 3 different cohorts, with clinically relevant differences in BP response by genotype, such that each variant allele was associated with ≈3.5 to 4.5 mm Hg greater BP reduction with a β-blocker. The data for 1 variant are shown in Figure (diastolic BP response by SLC25A31 rs201279313 genotype). Our findings have some important clinical implications: (1) β-blocker use should be considered for hypertension management for some blacks with uncomplicated hypertension. (2) Further investigations of these 2 genetic loci may be useful to identify the blacks who respond to β-blockers. (3) If shown in future studies to be sufficiently predictive, these genetic variants have the potential to be used in personalized antihypertensive treatment of blacks.
Unipolar Carotid Sinus Stimulation (p 585)
Implantable devices electrically stimulating the carotid sinus have been developed for the treatment of resistant hypertension and heart failure. The first-generation device (Rheos) applied bilateral localized field stimulation through bipolar electrodes placed around the carotid sinuses but is no longer available. The second-generation device (neo), which is approved and clinically applied in Europe, uses a small unilateral unipolar disk electrode to decrease invasiveness and to improve battery life, but unlike the first-generation device has not been tested in a controlled clinical trial. In this issue of Hypertension, Heusser et al applied state-of-the-art methodology to assess acute responses to unilateral unipolar electric carotid sinus stimulation in patients with resistant hypertension. The authors observed acute reductions in blood pressure and sympathetic activity with electric carotid sinus stimulation. The response was variable, and a relatively large proportion of patients reported side effects caused by off-target electric stimulation. When electric stimulation was adjusted to tolerable intensities, acute efficacy was markedly attenuated. In comparison, blood pressure reduction with bilateral bipolar stimulation was more robust and better tolerated. Thus, introduction of the less invasive approach may have euthanized efficacy. Pending results from controlled clinical trials, electric carotid sinus stimulation should not be applied in routine clinical care. The fact that compared with medications, device-based treatments that require much less rigorous clinical testing in many countries should be scrutinized.
Low Salt, Circadian Dysfunction, and Hypertension (p 661)
What is the ideal blood pressure for good human health? Such a simple question, yet the answer remains complex. The 2014 JNC8 report suggested a less aggressive drug-initiated approach to control blood pressure, advising antihypertensive interventions in young patients with >90 mm Hg diastolic, and >150/90 mm Hg in elderly patients, a more lenient treatment strategy than its predecessor 2003 JNC7. In contrast, recent results from the SPRINT trial suggest that aggressive blood pressure reduction to <120 mm Hg diastolic does offer increased health benefit in older, nondiabetic patients at increased cardiovascular risk. These standards do not take into account the natural variability in blood pressure across the day, the circadian rhythm. The current study highlights the importance of rhythmically dipping blood pressure, in hypertensive and normotensive conditions, albeit in mice. In these studies, experimental hypertension induced by angiotensin II infusion in mice with a genetically disrupted circadian rhythm caused nondipping hypertension (Figure, upper line graphs). Surprisingly, a low-salt diet given to the mice was also able to induce nondipping blood pressure in the circadian rhythm dysfunctional mice (Figure, lower line graphs), which may bear some significance to recent human studies, suggesting that there are caveats to absolute benefits of sodium restriction. Indeed, the current data underscore the significance of time of day variation in blood pressure (and its measurement via ambulatory monitoring), with even modest changes in dipping blood pressure profile causing pathological vascular remodeling. Moreover, sleep disorders, shift work, aging, and even silent circadian decline may produce adverse and unexpected interactions in hypertension and resultant cardiovascular disease.
- © 2016 American Heart Association, Inc.