Renin-angiotensin system blockers may create more risk than reward for sodium-depleted cardiovascular patients with high plasma renin levels.

Background: Four recent reports revealed differences in survival rates among treated cardiovascular patients taking renin-angiotensin system-blocking drugs. Patients with higher on-treatment plasma renin activity (PRA) levels died sooner of cardiovascular mortality than those with lower levels. We investigated whether excessive sodium depletion might have induced the higher PRA levels and contributed to the greater morbidity and mortality.

Plasma renin activity (PRA) levels and antihypertensive drug use in a large healthcare system.

Background: Although hypertension guidelines have utility in treating uncomplicated hypertension, they often overlook the pathophysiologic basis and heterogeneity of hypertension. This may explain the relatively poor hypertension control rates. A proposed approach is to guide addition and subtraction of medications using ambulatory plasma renin activity (PRA) values.

Enduring direct association of baseline plasma renin activity with all-cause and cardiovascular mortality in hypertensive patients.

Background: Plasma renin activity (PRA) has been associated with cardiovascular disease mortality (CVD) events among hypertensive patients. We now report a long-term follow-up to assess the enduring association of PRA to CVD and all-cause mortality.

Methods: Participants (3,791) in a systematic hypertension treatment study had entry systolic blood pressure (BP) ≥140 mm Hg and mean age 52.

The plasma renin test reveals the contribution of body sodium-volume content (V) and renin-angiotensin (R) vasoconstriction to long-term blood pressure.

Body sodium works together with the plasma renin-angiotensin system to ensure adequate blood flow to the tissues. Body sodium content determines the extracellular fluid (ECF) volume ensuring that, with each heart beat, a sufficient volume of fluid is delivered into the arterial space. At the same time the kidneys monitor ECF volume and blood pressure (BP), so that the juxtaglomerular cells can adjust their net secretion rate of renin to maintain an appropriate plasma renin activity (PRA) level.

A feasibility study of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer.

Purpose: Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer.

Experimental Design: Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled.

Pressor responses to antihypertensive drug types.

Background: Pressor responses to antihypertensive drugs are not addressed in treatment guidelines although they have been described in various clinical situations. We now report the incidence of pressor responses to initiation of monotherapy using four antihypertensive drug types, and the influence of plasma renin activity (PRA) status, among participants in a worksite-based antihypertensive treatment program.

Methods: Systolic blood pressure (SBP) response was evaluated among 945 participants with no prior treatment who were given either a diuretic or calcium-channel blocker (natriuretic antivolume V drugs, n = 537) or a beta-blocker or angiotensin-converting enzyme (ACE) inhibitor (antirenin R drugs n = 408).

Plasma Renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial.

Background: Undefined pathophysiologic mechanisms likely contribute to unsuccessful antihypertensive drug therapy. The renin test-guided therapeutic (RTGT) algorithm is based on the concept that, irrespective of current drug treatments, subnormal plasma renin activity (PRA) (<0.65 ng/ml/h) indicates sodium-volume excess "V" hypertension, whereas values >or=0.

Aliskiren fails to lower blood pressure in patients who have either low PRA levels or whose PRA falls insufficiently or reactively rises.

Background: Suppressed baseline plasma renin activity (PRA) levels or large reactive increases in renin secretion are two possible reasons for treatment failure with antirenin system drugs.

Methods: To investigate their prevalence we reanalyzed data from three published clinical trials of the renin inhibitor aliskiren.

Results: Aliskiren failed to lower systolic blood pressure (SBP) by at least 10 mm Hg in half of all patients.

Effects of angiotensin receptor blockers on ambulatory plasma Renin activity in healthy, normal subjects during unrestricted sodium intake.

Background: Plasma renin activity (PRA), measured under controlled conditions, is a marker of the degree and persistence of renin-angiotensin system blockade.

Methods: Two similarly designed five-way crossover studies evaluated angiotensin II type 1 (AT1) receptor blockade-induced changes in PRA in quietly seated, ambulatory volunteers who were ingesting uncontrolled diets. At weekly intervals, PRA was measured during the 24 h after administration of placebo, olmesartan medoxomil (20 or 40 mg), or valsartan (80 or 160 mg) (Study CS866-445), or placebo, olmesartan medoxomil (40 mg), valsartan (160 or 320 mg), or irbesartan (300 mg) (Study CS866-448).

Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness.

A review of six clinical trials of aliskiren involving >5,000 patients with mild to moderate hypertension indicated that this first of a new class of orally active antihypertensive drugs is no more effective than angiotensin-converting enzyme inhibitors (CEIs), angiotensin receptor blockers (ARBs), or diuretics for lowering blood pressure. The starting dose is 150 mg; 300 mg is usually more effective, but 600 mg is no better than 300 mg. Aliskiren in combination with a diuretic appeared to lower blood pressure more than an aliskiren-ARB combination, but still failed to control blood pressure (<140/90) in 50% of the patients.

Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.

Background: In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan.

Objectives: The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy.

Low renin hypertensive states: perspectives, unsolved problems, future research.

Some causes of low renin hypertension are familial with known genetic bases. One of them, primary aldosteronism, is specifically treatable by mineralocorticoid receptor blockers or by surgery, and has at least two different familial varieties. These have provided insights into its natural history, with long normotensive and normokalemic phases, and variable expression within the same family.

Beyond hypertension toward guidelines for cardiovascular risk reduction.

Background: Most current clinical guidelines focus primarily on the management of individual cardiovascular risk factors, such as high blood pressure (BP), hypercholesterolemia, or diabetes. A more appropriate clinical approach to reducing cardiovascular disease risk would be based on a comprehensive evaluation of risk profile, and accurate stratification of global (absolute) risk in individual patients. We propose that global risk should be used as the main determinant of whom to treat, how to treat, and how much to treat.