Blood Pressure Control Provides Less Cardiovascular Protection in Adults With Than Without Apparent Treatment‐Resistant Hypertension

Hypertension control may offer less protection from incident cardiovascular disease (CVD_i) in adults with than without apparent treatment‐resistant hypertension (aTRH), ie, blood pressure uncontrolled while taking three or more antihypertensive medications or controlled to <140/<90 mm Hg while taking four or more antihypertensive medications. Electronic health data were matched to health claims for 2006–2012. Patients with CVD_i in 2006–2007 or with untreated hypertension were excluded, leaving 118,356 treated hypertensives, including 40,690 with aTRH, and 460,599 observation years. Blood pressure and medication number were determined by all clinic visit means from 2008 to CVD_i or end of study. Primary outcome was first CVD_i (stroke, coronary heart disease, heart failure) from hospital and emergency department claims. Controlling for age, race, sex, diabetes, chronic kidney disease, and statin use, hypertension control afforded less CVD_i protection in patients with aTRH (hazard ratio, 0.87; 95% confidence interval, 0.82–0.93) than without aTRH (hazard ratio, 0.69; 95% confidence interval, 0.65–0.74; P<.001). Strategies beyond hypertension control may prevent more CVD_i in patients with aTRH.     

Add‐On Use of Eplerenone Is Effective for Lowering Home and Ambulatory Blood Pressure in Drug‐Resistant Hypertension

The authors aimed to investigate the blood pressure (BP)–lowering ability of eplerenone in drug‐resistant hypertensive patients. A total of 57 drug‐resistant hypertensive patients whose home BP was ≥135/85 mm Hg were investigated. The patients were randomized to either an eplerenone group or a control group and followed for 12 weeks. The efficacy was evaluated by clinic, home, and ambulatory BP monitoring. Urinary albumin, pulse wave velocity, and flow‐mediated vasodilation (FMD) were also evaluated. Home morning systolic BP (148±15 vs 140±15 mm Hg) and evening systolic BP (137±16 vs 130±16 mm Hg) were significantly lowered in the eplerenone group (n=35) compared with baseline (both P<.05), while unchanged in the control group (n=22). BP reductions in the eplerenone group were most pronounced for ambulatory awake systolic BP (P=.04), awake diastolic BP (P=.004), and 24‐hour diastolic BP (P=.02). FMD was significantly improved in the eplerenone group. In patients with drug‐resistant hypertension, add‐on use of eplerenone was effective in lowering BP, especially home and ambulatory awake BP.     

Red Blood Cell Distribution Width Is Associated With All‐Cause and Cardiovascular Mortality in Hemodialysis Patients

Red blood cell distribution width (RDW) is an index of red blood cell variability that is usually used to differentiate the cause of anemia. However, clinical evidence for the relationship between RDW and mortality in hemodialysis patients is still lacking. We performed a single center, prospective longitudinal study. During more than 5 years of follow‐up in 80 patients undergoing maintenance hemodialysis, 34 patients (42.5%) died. In the Kaplan–Meier curve analyses, higher RDW levels (≥ 14.9%) were significantly associated with all‐cause and cardiovascular mortality (log‐rank test, P < 0.05, each). In multivariate Cox proportional hazard models, each 1.0% increase in RDW value predicted an estimated 25% higher risk of mortality (P < 0.05) and a 40% higher risk of cardiovascular mortality (P < 0.05). In conclusion, higher RDW value was a significant predictor for all‐cause and cardiovascular mortality in patients undergoing maintenance hemodialysis.     

Blood Pressure and All‐Cause Mortality by Level of Cognitive Function in the Elderly: Results From a Population‐Based Study in Rural Greece

This study aimed to investigate whether the effect of blood pressure (BP) on mortality differs by levels of cognitive function. The associations of brachial systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure with all‐cause mortality were prospectively explored (follow‐up 7.0±2.2 years) in 660 community‐dwelling individuals ( ≥ 60 years) using adjusted Cox models, stratified by cognitive impairment (Mini‐Mental State Examination [MMSE] <24). No association between brachial BP variables and mortality was shown for the total sample in quartiles analysis; however, MAP in the highest quartile, compared with the second, was associated with mortality (hazard ratio, 1.85; 95% confidence intervals, 1.09–3.12) among cognitively impaired individuals. The fractional‐polynomials approach for BP confirmed this finding and further showed, solely in the MMSE <24 subcohort, U‐shaped trends of MAP and systolic BP, with increased mortality risk in extremely low or high values; no such pattern was evident for patients with MMSE ≥24. Elderly individuals with cognitive impairment might be more susceptible to the detrimental effects of low and elevated MAP and systolic BP.     

Low Blood Pressure Is Associated With Greater Risk for Cardiovascular Events in Treated Adults With and Without Apparent Treatment‐Resistant Hypertension

Apparent treatment‐resistant hypertension (aTRH) may confound the reported relationship between low blood pressure (BP) and increased cardiovascular disease (CVD) in treated hypertensive patients. Incident CVD was assessed in treated hypertensive patients with and without aTRH (BP ≥140 and/or ≥90 mm Hg on ≥3 medications or <140/<90 mm Hg on ≥4 BP medications) at three BP levels: 1: <120 and/or <70 mm Hg and <140/<90 mm Hg; 2: 120–139/70–89 mm Hg; and 3: ≥140 and/or ≥90 mm Hg. Electronic health data were matched to emergency and hospital claims for incident CVD in 118 356 treated hypertensive patients. In adults with and without aTRH, respectively, CVD was greater in level 1 versus level 2 (multivariable hazard ratio, 1.88 [95% confidence interval [CI], 1.70–2.07]; 1.71 [95% CI, 1.59–1.84]), intermediate in level 1 versus level 3 (hazard ratio, 1.32 [95% CI, 1.21–1.44]; 0.99, [95% CI, 0.92–1.07]), and lowest in level 2 versus level 3 (hazard ratio, 0.70 [95% CI, 0.65–0.76]; 0.58, [95% CI, 0.54–0.62]). Low treated BP was associated with more CVD than less stringent BP control irrespective of aTRH.     

Role of Ambulatory Blood Pressure Monitoring in Resistant Hypertension

Ambulatory blood pressure monitoring has gained growing popularity in the diagnosis and treatment of essential hypertension for several reasons, such as the lack of the so-called white-coat effect, the greater reproducibility as compared with clinic blood pressure, the ability to provide information on blood pressure phenomena of prognostic value and the closer relationship with the risk of cardiovascular morbidity and mortality. All the above-mentioned main features of ambulatory blood pressure monitoring are also true for resistant hypertension. In addition, however, in resistant hypertension, blood pressure monitoring allows one to precisely define the diagnosis of this clinical condition, by excluding the presence of white-coat hypertension, which is responsible for a consistent number of “false” resistant hypertensive cases. The approach also allows one to define the patterns of blood pressure variability in this clinical condition, as well as its relationships with target organ damage. Finally, it allows one to assess the effects of therapeutic interventions, such as renal nerves ablation, aimed at improving blood pressure control in this hypertensive state. The present paper will critically review the main features of ambulatory blood pressure monitoring in resistant hypertension, with particular emphasis on the diagnosis and treatment of this high-risk hypertensive state.     

Plasma Cystine Levels and Cardiovascular and All‐Cause Mortality in Hemodialysis Patients

Oxidative stress accelerates the development of cardiovascular disease. Plasma cystine, a thiol oxidative stress marker, is related to several established factors for cardiovascular disease risk and prognosis. Although a comprehensive oxidative stress index is clinically required for hemodialysis patients with high oxidative stress, there are few reports concerning thiol oxidative stress markers predicting their prognosis. We investigated the relationship between plasma amino acids including cystine levels and cardiovascular disease‐related and all‐cause mortality in 132 maintenance hemodialysis patients. Higher cystine levels were associated with old age, longer hemodialysis duration, hemodialysis‐associated hypotension, higher cardiothoracic ratio, higher blood urea nitrogen, and lower ankle‐brachial index. Multivariate Cox regression analysis revealed that high plasma cystine was independently related with both cardiovascular disease mortality and all‐cause mortality. Thus, high plasma cystine levels predict the prognosis of hemodialysis patients. High cystine levels necessitate a careful investigation for the cause of oxidative stress and comorbidities like vascular injury.     

Acute Sildenafil Use Reduces 24‐Hour Blood Pressure Levels in Patients With Resistant Hypertension: A Placebo‐Controlled,Crossover Trial

The authors previously demonstrated that acute administration of sildenafil—a phosphodiesterase 5 (PDE5) inhibitor—improves hemodynamic parameters in patients with resistant hypertensive (RH), but its effect on ambulatory blood pressure monitoring (ABPM) is unknown. This interventional, nonrandomized, single‐blinded, placebo‐controlled, crossover trial included 26 patients with RH. A dose of sildenafil (187.5mg) was given, and after a washout period of 14 days the patients received a single oral dose of placebo and the protocol was repeated. The patients underwent 24‐hour ABPM recordings the day before and immediately after the protocols. The reduction of systolic (−8.8±1.4 vs 1.3±1.2 mm Hg, P=.02), diastolic (−5.3±3.3 vs 1.8±1.1 mm Hg, P=.03), and mean (−7.9±3.6 vs 0.8±0.9 mm Hg, P=.01) 24‐hour BP were found after the use of sildenafil compared with placebo. Improvement in daytime BP levels was also observed (systolic −6.0±4.7 vs 4.4±1.5 mm Hg [P=.02] and mean −4.8±3.9 vs 3.5±1.4 mm Hg [P=.02] for sildenafil vs placebo, respectively). Considering its antihypertensive effect, sildenafil may represent a therapeutic option for RH treatment.

The pathogenesis of resistant hypertension (RH) is multifactorial,¹ impacting a worse prognosis when compared with controlled hypertension.² The mechanisms of resistance to antihypertensive therapy are not completely understood and can be modulated by several interrelated factors such as (1) hyperactivation of the sympathetic nervous and renin‐angiotensin‐aldosterone system,³, ⁴ (2) volume expansion,⁵ (3) endothelial dysfunction,⁶, ⁷ (4) inflammatory processes,⁸ and (5) increased peripheral vascular resistance.⁹ Although there is little evidence related to populations with RH, effective blood pressure (BP) control reduces the risk of cardiovascular events in general hypertensive patients and should be targeted.¹⁰ New drug therapies have been proposed, but BP control remains a challenge for patients with RH.¹¹ Phosphodiesterase type 5 (PDE5) inhibitors are safe and effective drugs presenting vasodilatory effects that provide office BP reductions in untreated¹² and resistant hypertensive patients.¹³ Recently, our group has shown an improvement in hemodynamic parameters after acute administration of sildenafil in patients with RH.¹⁴ Although ambulatory BP monitoring (ABPM) is superior to casual BP for predicting organ damage in hypertensive patients,¹⁵, ¹⁶ the influence of sildenafil on ABPM was never assessed in patients with RH.The present study sought to evaluate the effects of sildenafil on ABPM in patients with RH. We hypothesized that acute administration of sildenafil—a PDE5 inhibitor—compared with placebo improves 24‐hour BP levels in patients with resistance to antihypertensive therapy.     

Brachial Pulse Pressure and Cardiovascular or All‐Cause Mortality in the General Population: A Meta‐Analysis of Prospective Observational Studies

This study aimed to quantitatively evaluate the predictive value of brachial pulse pressure and cardiovascular or all‐cause mortality in the general population based on prospective observational studies by conducting a meta‐analysis. Only prospective observational studies investigating baseline brachial pulse pressure and cardiovascular or all‐cause mortality risk were selected from PubMed and Embase databases until July 2013. Fourteen studies involving 510,456 participants were analyzed. Pooled risk ratio (RR) of cardiovascular and all‐cause mortality for the highest vs lowest brachial pulse pressure category was 1.80 (95% confidence interval [CI], 1.49–2.17) and 1.32 (95% CI, 1.23–1.41), respectively. Pooled RR of cardiovascular and all‐cause mortality per 10 mm Hg pulse pressure increment was 1.13 (95% CI, 1.10–1.17) and 1.09 (95% CI, 1.07–1.11), respectively. Wide brachial pulse pressure is associated with greater risk of cardiovascular and all‐cause mortality. However, more well‐designed studies specifically on age and sex are needed to further confirm these findings.