
Hypertension is an important contributor to progression of nondiabetic chronic kidney disease (CKD). Compelling observational evidence indicates that the divergence of blood pressure (BP) away from an ideal range in either direction is associated with a progressive rise in the risk of mortality and cardiovascular and renal disease progression. To date, various clinical trials and meta-analyses examining strict versus less intensive BP control in nondiabetic CKD have not conclusively demonstrated a renal advantage of one BP-lowering approach over another, except in certain subgroups such as proteinuric patients where evidence is circumstantial. As recent data have come to light suggesting that intensive BP control yields superior survival and cardiovascular outcomes in patients at high risk for cardiovascular disease, interest in the prospect of whether such benefit extends to individuals with CKD has surged. This review is a comprehensive analysis of antihypertensive literature in nondiabetic renal disease, with a particular emphasis on BP target.
Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair Sana M. Al-Khatib, MD, MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA
Neurovascular coupling, the relationship between cerebral blood flow and neuronal activity, is attenuated in patients with impaired executive function. We tested the hypothesis that peripheral vascular function may associate with executive function in older subjects with cardiovascular risk factors and that treatment with the antioxidant L-arginine would improve both vascular and executive function. Nineteen subjects with type 2 diabetes mellitus and/or controlled hypertension were enrolled. Subjects were treated with L-arginine or placebo for 4 days in a randomized, double-blinded, cross-over study. Brachial artery vascular function, peripheral artery tonometry, and Trail Making Test Part B testing were performed on day 1 and day 4 during each condition. L-arginine significantly reduced the digital reactive hyperemia index, and the comparison of changes against placebo was significant (P = .01). With executive function testing, we observed a significant interaction between treatment and order. Restricting the analysis to the first treatment period, subjects treated with placebo decreased their Trail Making Test Part B times by 57.3 ± 52.5 seconds from day 1 to day 4 (P = .01) while those treated with arginine had no significant change (6.4 ± 18.4 seconds worse, P = .37). In addition, L-arginine was associated with increased mean arterial pressure from 88 ± 9 mm Hg to 92 ± 11 mm Hg, which trended toward significance. L-arginine treatment worsened digital microvascular and executive function in older subjects with cardiovascular risk factors. These data further support a link between vascular and executive function.
Aerobic endurance exercise (AEX) is an effective treatment in the prevention and management of high blood pressure (BP). Growing evidence suggests potential benefits from isometric handgrip (IHG) exercise, which may promote similar or even larger reductions in BP than AEX. We compared the effects of home-based AEX and home-based IHG on BP. Sixty healthy individuals (31 men; mean age, 33.1 years; mean BP, 126.9 ± 1.6/84.7 ± 1.1 mm Hg) were randomized to IHG, AEX, or a control group. Both exercise interventions were performed in the home environment. The IHG group performed daily 4 × 2 minutes sustained grips at 30% of maximal volitional contraction. Participants in the AEX group were advised to perform at least 150 min/wk of aerobic exercise at moderate intensity. Outcome measurements were assessed at baseline and 8 weeks of follow-up. Compared with the control group, AEX resulted in a larger reduction in ambulatory BP; both AEX and IHG exercise tended to induce larger reductions in office systolic BP, and office diastolic BP was significantly more reduced after AEX but not IHG exercise. Responses to training were not significantly different between both the exercise interventions. Eight weeks of home-based AEX results in significant reductions in both ambulatory BP and office BP in healthy adults, whereas IHG reduces only office BP.