Potassium intake: the Cinderella electrolyte.

Dietary guidelines recommend intake targets for some essential minerals, based on observational and experimental evidence relating mineral intake levels to health outcomes. For prevention of cardiovascular disease, reducing sodium intake and increasing potassium intake are the principal tools. While reducing sodium intake has received greatest public health priority, emerging evidence suggests that increasing potassium intake may be a more important target for cardiovascular prevention. Increased potassium intake reduces blood pressure and mitigates the hypertensive effects of excess sodium intake, and the recent large Phase III SSaSS trial reported that increasing potassium intake (and reducing sodium intake) in populations with low potassium intake and high sodium intake, through salt substitution (25% KCl, 75%NaCl), reduces the risk of stroke in patients at increased cardiovascular risk. As key sources of potassium intake include fruit, vegetables, nuts, and legumes, higher potassium intake may be associated with healthy dietary patterns. The current review makes the case that increasing potassium intake might represent a more advantageous dietary strategy for prevention of cardiovascular disease. Future research should focus on addressing the independent effect of potassium supplementation in populations with low or moderate potassium intake, and determine effective strategies to increase potassium intake from diet.

Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening. METHODS: A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure (BP) parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes. RESULTS: Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory BP parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48-2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12-1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01-5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92-3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01-1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10-1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25 734 patients) were omitted (Pheterogeneity<0.05 for most outcomes), the above effect of evening dosing attenuated with no significant effect on 24/48-hour ambulatory blood pressure, day-time BP, and major adverse cardiac event and smaller reduction in night-time ambulatory SBP and DBP. CONCLUSIONS: Evening dosing of antihypertensive drugs significantly reduced ambulatory BP parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time BP, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects.

Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials.

OBJECTIVE: Use of amlodipine for treatment of arterial hypertension and stable coronary artery disease (CAD) is sometimes limited by occurrence of peripheral edema and headache. We aimed to explore the true magnitude of this phenomenon by determining the rate and placebo-adjusted rate of these side effects. METHODS: We performed a meta-analysis by including all randomized, placebo-controlled trials reporting edema and headache with amlodipine in patients with arterial hypertension and CAD. Placebo-adjusted rate (%) was determined as follows: (SE amlodipine % - SE placebo %)/SE amlodipine %. RESULTS: Data from 7226 patients of 22 trials were analyzed. Rate of edema was higher on amlodipine vs. placebo (16.6 vs. 6.2%, risk ratio: 2.9, 95% CI: 2.50-3.36, P < 0.0001). The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine. Treatment with low/medium doses (2.5-5 mg) resulted in lower rates of edema (risk ratio: 2.01, 95% CI: 1.41-2.88, P = 0.0001) vs. high dose (10 mg) (risk ratio: 3.08, 95% CI 2.62-3.60, P < 0.0001, Pforinteraction = 0.03). Incidence of headache was reduced using amlodipine vs. placebo (7.9 vs. 10.9%, risk ratio: 0.77, 95% CI: 0.65-0.90, P = 0.002) and was driven by use of low/medium doses (risk ratio: 0.52, 95% CI: 0.40-0.69, P < 0.00001 vs. risk ratio: 0.92, 95%-CI: 0.74-1.15, P = 0.45, for high doses, Pforinteraction = 0.002). CONCLUSION: Although risks of peripheral edema are three-fold higher on amlodipine, up to one-third of edema cases on amlodipine might not be induced by amlodipine. Headache is reduced on amlodipine treatment, mainly driven by use of this drug at low/medium doses.

Resistant hypertension: what the cardiologist needs to know.

Treatment-resistant hypertension (TRH) affects between 3 and 30% of hypertensive patients, and its presence is associated with increased cardiovascular morbidity and mortality. Until recently, the interest on these patients has been limited, because providing care for them is difficult and often frustrating. However, the arrival of new treatment options [i.e. catheter-based renal denervation (RDN) and baroreceptor stimulation] has revitalized the interest in this topic. The very promising results of the initial uncontrolled studies on the blood pressure (BP)-lowering effect of RDN in TRH seemed to suggest that this intervention might represent an easy solution for a complex problem. However, subsequently, data from controlled studies have tempered the enthusiasm of the medical community (and the industry). Conversely, these new studies emphasized some seminal aspects on this topic: (i) the key role of 24 h ambulatory BP and arterial stiffness measurement to identify 'true' resistant patients; (ii) the high prevalence of secondary hypertension among this population; and (iii) the difficulty to identify those patients who may profit from device-based interventions. Accordingly, for those patients with documented TRH, the guidelines suggest to refer them to a hypertension specialist/centre in order to perform adequate work-up and treatment strategies. The aim of this review is to provide guidance for the cardiologist on how to identify patients with TRH and elucidate the prevailing underlying pathophysiological mechanism(s), to define a strategy for the identification of patients with TRH who may benefit from device-based interventions and discuss results and limitations of these interventions, and finally to briefly summarize the different drug-based treatment strategies.

Beyond salt: lifestyle modifications and blood pressure.

Lifestyle changes have been shown to effect significant blood pressure (BP) reductions. Although there are several proposed neurohormonal links between weight loss and BP, body mass index itself appears to be the most powerful mediator of the weight-BP relationship. There appears to be a mostly linear relationship between weight and BP; as weight is regained, the BP benefit is mostly lost. Physical activity, but more so physical fitness (the physiological benefit obtained from physical activity), has a dose-dependent BP benefit but reaches a plateau at which there is no further benefit. However, even just a modest physical activity can have a meaningful BP effect. A diet rich in fruits and vegetables with low-fat dairy products and low in saturated and total fat (DASH) is independently effective in reducing BP. Of the dietary mineral nutrients, the strongest data exist for increased potassium intake, which reduces BP and stroke risk. Vitamin D is associated with BP benefit, but no causal relationship has been established. Flavonoids such as those found in cocoa and berries may have a modest BP benefit. Neither caffeine nor nicotine has any significant, lasting BP effect. Biofeedback therapies such as those obtained with device-guided breathing have a modest and safe BP benefit; more research is needed before such therapies move beyond those having an adjunctive treatment role. There is a strong, linear relationship between alcohol intake and BP; however, the alcohol effects on BP and coronary heart disease are divergent. The greatest BP benefit seems to be obtained with one drink per day for women and with two per day for men. This benefit is lost or attenuated if the drinking occurs in a binge form or without food. Overall, the greatest and most sustained BP benefit is obtained when multiple lifestyle interventions are incorporated simultaneously.

Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate--a meta-analysis of randomized trials.

OBJECTIVE: Peripheral edema is considered to be a common and annoying adverse effect of calcium channel blockers (CCBs). It has been thought to occur secondary to arteriolar dilatation causing intracapillary hypertension and fluid extravasation. We aimed to evaluate the incidence and withdrawal rate of peripheral edema with CCBs. METHODS: A systematic search was made in PubMed, EMBASE and CENTRAL from 1980 to January 2011 for randomized clinical trials reporting peripheral edema with CCBs in patients with hypertension. Trials enrolling at least 100 patients in the CCB arm and lasting at least 4 weeks were included in the analysis. Both the incidence and withdrawal rate due to edema were pooled by weighing each trial by the inverse of the variance. Head-to-head comparison was done to evaluate the risk of edema between newer lipophilic dihydropyridine (DHP) CCBs and older DHPs. RESULTS: One hundred and six studies with 99 469 participants, mean age 56 ± 6 years, satisfied our inclusion criteria and were included in this analysis. The weighted incidence of peripheral edema was significantly higher in the CCBs group when compared with controls/placebo (10.7 vs. 3.2%, P < 0.0001). Similarly, the withdrawal rate due to edema was higher in patients on CCBs compared with control/placebo (2.1 vs. 0.5%, P < 0.0001). Both the incidence of edema and patient withdrawal rate due to edema increased with the duration of therapy with CCBs reaching 24 and 5%, respectively, after 6 months. The risk of peripheral edema with lipophilic DHPs was 57% lower than with traditional DHPs (relative risk 0.43; 95% confidence interval 0.34-0.53; P < 0.0001). Incidence of peripheral edema in patients on DHPs was 12.3% compared with 3.1% with non-DHPs (P < 0.0001). Edema with high-dose CCBs (defined as more than half the usual maximal dose) was 2.8 times higher than that with low-dose CCBs (16.1 vs. 5.7%, P < 0.0001). CONCLUSION: The incidence of peripheral edema progressively increased with duration of CCB therapy up to 6 months. Over the long term, more than 5% of patients discontinued CCBs because of this adverse effect. Edema rates were lower with both non-DHPs and lipophilic DHPs.

A novel pathway for the management of hypertension for hospitalized patients.

About 65 million Americans, one fourth of the adult population in the United States, and over 1 billion people worldwide have hypertension (HTN). HTN therefore is present in 1 of every 4 patients admitted to any US hospital. Surprisingly, no guidelines are available for the management of inpatient HTN. Based on a comprehensive search of the literature we are proposing a pathway for the management of HTN in nonpregnant hospitalized patients. The pathway provides a definition and clinical assessment of HTN for patients admitted to the hospital. The assessment is followed by an organ/system based therapeutic approach specifying timing, blood pressure goals, recommended antihypertensive drug therapy and the sequence of add-on drugs. The pathway specifically discusses assessment and management of HTN in patients with (1) acute aortic syndrome, (2) acute neurologic syndrome, (3) acute coronary syndrome, (4) congestive heart failure, (5) renal failure, and (6) secondary forms. Finally, the pathway provides a step by step recommendation for the management of in hospital HTN and of hypertensive emergencies.

Treatment of elderly hypertensive patients with a delayed-release verapamil formulation in a community-based trial.

This report of a practice-based clinical trial describes an open-label, multicenter dose-titration study of an elderly (age >or=65 years) subset of patients (N=628) with systolic blood pressures between 140 and 179 mm Hg or diastolic blood pressures between 90 and 109 mm Hg, to assess the effects of the Chronotherapeutic Oral Drug Absorption System (CODAS) formulation of verapamil hydrochloride. After starting 200 mg/d at bedtime, dosing was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure of <140/<90 mm Hg using morning blood pressure measurements. Target blood pressure was reached in 57.1% of the elderly patients with CODAS verapamil monotherapy. A diastolic response (<90 mm Hg or a 10 mm Hg reduction from baseline) was achieved in 89.5% of these subjects, and a systolic blood pressure response (<140 mm Hg or 10% reduction from baseline) was attained in 75.5%. The percentages of patients achieving target blood pressure or the diastolic and systolic blood pressure responses were comparable to those previously reported for younger patients. It is notable that although 359 of the 628 patients reached control on treatment, 182 of the remaining 269 noncontrolled patients were not titrated to higher doses, indicating that even with a well tolerated drug there may be reluctance among clinicians to increase doses. CODAS verapamil was found to be efficacious and well tolerated among elderly hypertensive patients in this community trial.

Vasodilatory edema: a common side effect of antihypertensive therapy.

Vasodilatory edema, a common adverse effect of antihypertensive therapy with vasodilators, is related to several mechanisms, including arteriolar dilatation (causing an increase in intracapillary pressure), stimulation of the renin-angiotensin-aldosterone system, and fluid volume retention. Vasodilatory edema is dose-dependent and most common with direct arteriolar dilators such as minoxidil or hydralazine, and in decreasing order of frequency with the dihydropyridine calcium antagonists, a-blockers, antiadrenergic drugs, and nondihydropyridine calcium antagonists. Not all dihydropyridine calcium antagonists are created equal with regard to vasodilatory edema. At an equal antihypertensive efficacy, lercanidipine and lacidipine are associated with less vasodilatory edema than amlodipine and nifedipine. The addition of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) to a dihydropyridine calcium antagonist significantly reduces vasodilatory edema. In contrast, the addition of a diuretic has little effect on vasodilatory edema. Thus, low-dose combination therapy (of a dihydropyridine calcium antagonist with either an ACE inhibitor or an ARB) may be preferred over high-dose monotherapy.