Faculty Bibliography

BACKGROUND: Diastolic dysfunction (DD) is associated with myocardial fibrosis mediated by inflammation. Higher levels of inflammation found in African Americans (AAs) may predict DD among asymptomatic individuals. We tested the hypothesis that high sensitivity C-reactive protein (hs-CRP), a biomarker of inflammation, is associated with DD in asymptomatic AAs. METHODS: We prospectively recruited 107 asymptomatic AAs without any history of cardiac, renal or inflammatory diseases or alcoholism. We measured hs-CRP and B-type Natriuretic peptide (BNP) levels and estimated left ventricular end diastolic pressure (LVEDP), mass and systolic function with echocardiography. Multivariate logistic regression analysis was used to define whether hs-CRP is an independent predictor of LVEDP. RESULTS: Among 107 subjects: the mean age was 48+/-10 yrs, 58 (54%) were men, 59 (55%) had diabetes (DM), 48 (45%) had hypertension (HTN), the mean BMI was 30.5+/-4.8 and the mean ejection fraction was 63.1+/-5.8%. DD was present in 56(52%) subjects, 38 (36%) of whom also had a high LVEDP. On multivariate analysis, hs-CRP was independently associated with DD [odds ratio 3.36 (95% CI= 1.07 - 10.5, p = 0.04]. There was a 61% and 133% increase in the prevalence of any DD and DD with high LVEDP, respectively, between the lowest and the highest hs-CRP quartiles. CONCLUSION: Diastolic dysfunction is prevalent among asymptomatic African Americans and it is independently associated with elevated level of hs-CRP, an inflammation marker.

J Clin Hypertens (Greenwich). (c) 2010 Wiley Periodicals, Inc. Patients with stage 2 hypertension (systolic blood pressure [SBP] >/=160 mm Hg and/or diastolic blood pressure [DBP] >/=100 mm Hg) are at high cardiovascular risk and require intensive blood pressure (BP)-lowering therapy. This randomized double-blind study is the first prospective trial specifically designed to evaluate the direct renin inhibitor aliskiren in patients with a mean sitting SBP >/=160 mm Hg and <180 mm Hg (the lower ranges of stage 2 systolic hypertension). After a 2- to 4-week washout period, 688 patients were randomized to once-daily aliskiren/hydrochlorothiazide (HCT) 150/12.5 mg or aliskiren 150 mg for 1 week and then double the doses for 11 weeks. Baseline BP was 167.1/95.0 mm Hg. At week 12, both aliskiren/HCT and aliskiren provided substantial BP reductions from baseline (30.0/12.6 mm Hg and 20.3/8.2 mm Hg, respectively). Aliskiren/HCT lowered BP significantly more than aliskiren (least-squares mean between-treatment differences [95% confidence interval] were -9.7 [-12.0 to -7.4] for SBP and -4.5 [-5.8 to -3.2] for DBP; both P<.0001). Similar BP reductions were seen in the subgroups of patients with isolated systolic hypertension and obesity. Aliskiren, with or without HCT, provides clinically significant BP reductions and may therefore be an effective treatment option in patients with stage 2 hypertension. J Clin Hypertens (Greenwich). 2010;12:917-926. (c) 2010 Wiley Periodicals, Inc

Hypertension is a risk factor for myocardial infarction (MI), stroke, and heart failure and precedes heart failure in 91% of cases. This becomes even more important considering that the number of Americans with hypertension increased from 65 million in 2005 to 72 million in 2007. If blood pressure is effectively controlled this risk can be minimized-blood pressure reductions as small as 2 mm Hg have been shown to reduce the risk of cardiovascular events by up to 10%. There is also strong evidence that blood pressure targets for populations at high risk of cardiovascular disease, including those with diabetes, coronary artery disease, and chronic kidney disease, should be lower than 140/90 mm Hg. The number and type of antihypertensive drugs have increased dramatically from 28 diuretics in 1972 to over 125 agents today, including fixed dose combination dosage forms. Beta blockers have been available for the treatment of hypertension since the 1960s. However, there has been resistance to using these agents in patients with diabetes and renal failure because of metabolic side effects, and in other patients because of tolerability concerns such as depression, weight gain, and impotence. Two newer beta blockers with vasodilatory effects (carvedilol and nebivolol) have proven efficacy and tolerability in patients with hypertension and appear to lack the adverse effects associated with older beta blockers. Carvedilol causes vasodilation by alpha blockade, and nebivolol via nitric oxide mechanisms. Both of these agents reduce peripheral vascular resistance and maintain cardiac output. Clinical trial evidence to date leads to the conclusion that beta blockers are strongly indicated post-MI and in all patients with left ventricular dysfunction regardless of symptoms. Their beneficial abilities include improvement of oxygen supply and demand (which can reduce myocardial ischemia), anti-arrhythmic properties, and beneficial effects on cardiac remodeling

Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving >/=3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central alpha-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (-15+/-14 mm Hg) were greater than for guanfacine (-12+/-13 mm Hg; P<0.05) but not greater than placebo (-14+/-14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (-9+/-12 mm Hg) more than placebo (-2+/-12 mm Hg) or guanfacine (-4+/-12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective.

BACKGROUND: The definition of a normal heart rate (HR) response to exercise stress testing in women is poorly understood, given that most studies describing a normative response were predominately based on male data. Measures of an attenuated HR response (chronotropic incompetence) and age-predicted HR have not been validated in asymptomatic women. We investigated the association between HR response to exercise testing and age with prognosis in 5437 asymptomatic women. METHODS AND RESULTS: Participants underwent a symptom-limited maximal stress test in 1992. HR reserve (change in HR from rest to peak), chronotropic index, and age-predicted peak HR were calculated. Deaths were identified to December 31, 2008. Mean age at baseline was 52+/-11 years, with 549 deaths (10%) over 15.9+/-2.2 years. Mean peak HR was inversely associated with age; mean peak HR=206-0.88(age). After adjusting for exercise capacity and traditional cardiac risk factors, risk of death was reduced by 3% for every 1-beat-per-minute increase in peak HR, and by 2% for every 1-beat-per-minute increase in HR reserve (P<0.001). Inability to achieve 85% age-predicted HR was not an independent predictor of mortality, but being >/=1 SD below the mean predicted HR or a chronotropic index <0.80 based on the prediction model established by this cohort were independent predictors of mortality (P<0.001 and P=0.023, respectively). CONCLUSIONS: Chronotropic incompetence is associated with an increased risk of death in asymptomatic women; however, the traditional male-based calculation overestimates the maximum HR for age in women. Sex-specific parameters of physiological HR response to exercise should be incorporated into clinical practice.