Showing papers by "Suzanne Oparil published in 2010"

Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report

Abstract: Obstructive sleep apnoea (OSA) and hyperaldosteronism are very common in subjects with resistant hypertension. We hypothesized that aldosterone-mediated chronic fluid retention may influence OSA severity in patients with resistant hypertension. We tested this in an open-label evaluation by assessing the changes in the severity of OSA in patients with resistant hypertension after treatment with spironolactone. Subjects with resistant hypertension (clinical blood pressure (BP) >or=140/90 mm Hg on >or=3 antihypertensive medications, including a thiazide diuretic and OSA (defined as an apnoea-hypopnoea index (AHI) >or=15) had full diagnostic, polysomnography before and 8 weeks after spironolactone (25-50 mg a day) was added to their ongoing antihypertensive therapy. In all, 12 patients (mean age 56 years and body mass index 36.8 kg m(-2)) were evaluated. After treatment with spironolactone, the AHI (39.8+/-19.5 vs 22.0+/-6.8 events/h; P<0.05) and hypoxic index (13.6+/-10.8 vs 6.7+/-6.6 events/h; P<0.05), weight and clinic and ambulatory BP were significantly reduced. Plasma renin activity (PRA) and serum creatinine were significantly higher. This study provides preliminary evidence that treatment with a mineralocorticoid receptor antagonist substantially reduces the severity of OSA. If confirmed in a randomized assessment, it will support aldosterone-mediated chronic fluid retention as an important mediator of OSA severity in patients with resistant hypertension.

Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension.

Abstract: Obstructive sleep apnea (OSA) and hypertension are both independently associated with increased cardiovascular risk1–7 Furthermore, approximately 50% of patients with OSA have a diagnosis of hypertension, whereas 30% of hypertensive patients have OSA8–11 Recently published evidence-based hypertension management guidelines identified OSA as an important identifiable cause of hypertension12 The association of OSA and hypertension is particularly marked among patients with resistant hypertension, with studies reporting an OSA prevalence of 80% to 85% in these patients13,14 BRIEF SUMMARY Current Knowledge/Study Rationale: We previously described a significant correlation between plasma aldosterone concentration and severity of obstructive sleep apnea in patients with resistant hypertension This investigation examines the relationship between aldosterone status and obstructive sleep apnea in patients with resistant hypertensive—with and without hyperaldosteronism Study Impact: The positive relationship between hyperaldosteronism and severity of obstructive sleep apnea (OSA) observed in the current analysis supports the hypothesis that aldosterone excess contributes to the development of OSA The results highlight the increased likelihood of hyperaldosteronism and OSA coexisting in patients with resistant hypertension and may explain, at least in part, the high prevalence of OSA in patients with resistant hypertension Hyperaldosteronism is common in patients with resistant hypertension Approximately 20% of patients with resistant hypertension have biochemical criteria consistent with primary aldosteronism15–18 In patients with resistant hypertension in whom we had diagnosed hyperaldosteronism, we observed that many had been previously diagnosed with OSA We, therefore, hypothesized that the 2 diseases may be mechanistically related, that is one contributing to the other Our center noted increased aldosterone excretion in patients with resistant hypertension who had symptoms of OSA19 We then showed that a significant correlation exists between plasma aldosterone concentration (PAC) and OSA severity in patients with resistant hypertension but not in normotensive control subjects14 Although we cannot directly infer causality from these studies, these results are consistent with the hypothesis that aldosterone excess may contribute to worsening severity of OSA To gain further insight into the association among resistant hypertension, OSA, and hyperaldosteronism, we evaluated the relationship between aldosterone levels and OSA severity in patients with resistant hypertension with and without hyperaldosteronism

Rapid Reversal of Left Ventricular Hypertrophy and Intracardiac Volume Overload in Patients With Resistant Hypertension and Hyperaldosteronism. A Prospective Clinical Study

Abstract: We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone ≥12 μg/24 hours and plasma renin activity ≤1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end-diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects ( P

Effect of Intensive Versus Standard Blood Pressure Lowering on Diastolic Function in Patients With Uncontrolled Hypertension and Diastolic Dysfunction

Abstract: Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of P P P P P P =0.58). The degree of improvement in annular relaxation velocity was associated with the extent of systolic blood pressure reduction, and patients with the lowest achieved systolic blood pressure had the highest final diastolic relaxation velocities.

Prehypertension: epidemiology, consequences and treatment

Abstract: The term prehypertension was coined in 1939 in the context of early studies that linked high blood pressure recorded during physical examination for life insurance purposes to subsequent morbidity and mortality. These studies demonstrated that individuals with blood pressure >120/80 mmHg, but <140/90 mmHg--the accepted value for the lower limit of the hypertensive range--had an increased risk of hypertension, cardiovascular disease and early death from cardiovascular causes. The prehypertension classification of blood pressure was later used by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to define a group of individuals at increased risk of cardiovascular events because of elevated blood pressure, an increased burden of other risk factors such as obesity, diabetes mellitus, dyslipidemia, and inflammatory markers, and evidence of organ damage for example, microalbuminuria, retinal arteriolar narrowing, increased carotid arterial intima-media thickness, left ventricular hypertrophy and coronary artery disease. Nonpharmacological treatment with lifestyle modifications such as weight loss, dietary modification and increased physical activity is recommended for all patients with prehypertension as these approaches effectively reduce risk of cardiovascular events. Pharmacological therapy is indicated for some patients with prehypertension who have specific comorbidities, including diabetes mellitus, chronic kidney disease and coronary artery disease.

Inhibition of transforming growth factor-β signaling induces left ventricular dilation and dysfunction in the pressure-overloaded heart

Abstract: This study utilized a transgenic mouse model that expresses an inducible dominant-negative mutation of the transforming growth factor (TGF)-beta type II receptor (DnTGFbetaRII) to define the structural and functional responses of the left ventricle (LV) to pressure-overload stress in the absence of an intact TGF-beta signaling cascade. DnTGFbetaRII and nontransgenic (NTG) control mice (male, 8-10 wk) were randomized to receive Zn(2+) (25 mM ZnSO(4) in drinking H(2)O to induce DnTGFbetaRII gene expression) or control tap H(2)O and then further randomized to undergo transverse aortic constriction (TAC) or sham surgery. At 7 days post-TAC, interstitial nonmyocyte proliferation (Ki67 staining) was greatly reduced in LV of DnTGFbetaRII+Zn(2+) mice compared with the other TAC groups. At 28 and 120 days post-TAC, collagen deposition (picrosirius-red staining) in LV was attenuated in DnTGFbetaRII+Zn(2+) mice compared with the other TAC groups. LV end systolic diameter and end systolic and end diastolic volumes were markedly increased, while ejection fraction and fractional shortening were significantly decreased in TAC-DnTGFbetaRII+Zn(2+) mice compared with the other groups at 120 days post-TAC. These data indicate that interruption of TGF-beta signaling attenuates pressure-overload-induced interstitial nonmyocyte proliferation and collagen deposition and promotes LV dilation and dysfunction in the pressure-overloaded heart, thus creating a novel model of dilated cardiomyopathy.

C-Reactive Protein-Mediated Vascular Injury Requires Complement

Abstract: Background— We previously demonstrated that vascular injury-induced neointima formation is exaggerated in human C-reactive protein (CRP) transgenic (CRPtg) compared to nontransgenic (NTG) mice. We now test the hypothesis that complement is required for this effect. Methods and Results— CRPtg and NTG with a normal complement system versus their counterparts lacking expression of complement component 3 (C3) protein (CRPtg/C3−/− and NTG/C3−/−) underwent carotid artery ligation. Twenty-eight days later, the injured vessels in CRPtg had thicker neointimas and more immunoreactive C3 in the surrounding adventitia compared with NTG. In CRPtg/C3−/−, there was no increase in neointimal thickness compared with NTG or NTG/C3−/−. Decreasing human CRP blood levels through administration of a selective antisense oligonucleotide eliminated the depletion of serum C3 associated with vascular injury and reduced immunoreactive C3 in the resultant lesions. In injured vessels, C3 colocalized with F4/80 (macrophage marker), and in vitro, human CRP elicited increased expression of C3 by bone marrow-derived macrophages. Conclusion— Human CRP exaggeration of neointima formation in injured mouse carotid arteries associates with decreased circulating C3 and increased tissue-localized C3. C3 elimination or pharmacological reduction of human CRP prevents CRP-driven exacerbation of the injury response. In the CRPtg model system, mouse C3 is essential for the effect of human CRP.

Long-term efficacy of a combination of amlodipine and olmesartan medoxomil±hydrochlorothiazide in patients with hypertension stratified by age, race and diabetes status: a substudy of the COACH trial

Abstract: A prespecified subgroup analysis of a 44-week open-label extension study is presented. The efficacy and safety of the combination of amlodipine (AML)+ olmesartan medoxomil (OM), with and without the addition of hydrochlorothiazide (HCTZ), were investigated in patients aged ⩾65 and <65 years, Blacks and non-Blacks and patients with and without type 2 diabetes. After an 8-week double-blind, placebo-controlled portion of the study, patients initiated therapy on AML 5+OM 40 mg per day, were uptitrated stepwise to AML 10+OM 40 mg per day, with the addition of HCTZ 12.5 mg, and 25 mg if blood pressure (BP) goal was not achieved (<140/90 or <130/80 mm Hg for patients with diabetes). Endpoints included the change from baseline in mean seated systolic BP, mean seated diastolic BP and achievement of BP goal. BP decreased from baseline for all treatments in each prespecified subgroup. By the end of the study, BP goal was achieved in 61.0% of patients aged ⩾65 years, 68.1% of patients aged <65 years, 63.3% of Blacks, 67.8% of non-Blacks, 26.9% of patients with diabetes and 72.9% of patients without diabetes. The combination of AML+OM±HCTZ was efficacious, safe and well tolerated by these subgroups.

Prevention of Microalbuminuria in Patients With Type 2 Diabetes: What Do We Know?

Abstract: Cardiovascular and chronic kidney disease are epidemic throughout industrialized societies. Diabetes leads to premature cardiovascular disease and is regarded by many as the most common etiological factor for chronic kidney disease. Because most studies of blood-pressure lowering agents in people with diabetes and hypertension have been conducted in individuals who already have some target organ damage, it is unclear whether earlier intervention could prevent or delay the onset of renal or systemic vascular disease. In early disease there is only a low possibility of observing cardiovascular or renal events; thus intervention trials in this population must rely on disease markers such as microalbuminuria. Accordingly, the authors review the evidence to support the use of microalbuminuria as a disease marker in diabetic patients based on its strong association with renal and cardiovascular events, and discuss recent trials that examine the impact of preventing or delaying the onset of microalbuminuria.

The Transcription Factor ETS-1 Mediates Proinflammatory Responses and Neointima Formation in Carotid Artery Endoluminal Vascular Injury

Abstract: The transcription factor ETS-1 is a critical mediator of vascular inflammation and hypertrophy in hypertension. We tested the hypothesis that ETS-1 is a mediator of proinflammatory responses and neointimal hyperplasia after balloon injury of the carotid artery. For this study, we took advantage of the availability of an ETS-1 dominant-negative (DN) peptide. Sprague-Dawley rats were assigned to treatment with ETS-1 DN, a mutant peptide (ETS-1 MU), or vehicle (Veh) and subjected to balloon injury of the carotid artery. After 2, 24 hours, and 14 days, the rats were euthanized, and both carotid arteries were processed for real-time polymerase chain reaction (2 hours), immunofluorescence and immunohistochemistry (24 hours), and morphometric analysis (14 days). ETS-1 mRNA was up regulated (2.4-fold) in injured carotid arteries. By immunofluorescence, we confirmed increased nuclear expression of ETS-1 24 hours postinjury. The carotid artery mRNA expression of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-2, P-selectin, E-selectin, vascular cell adhesion molecule, and intercellular adhesion molecule was increased 2 hours after injury. ETS-1 DN but not ETS-1 MU significantly reduced mRNA and protein expression for monocyte chemotactic protein-1, P-selectin, and E-selectin in injured arteries. These changes were accompanied by concomitant reductions in vascular monocyte and leukocyte infiltration. Moreover, treatment with ETS-1 DN but not ETS-1 MU resulted in a 50% reduction in neointima formation at day 14 after balloon injury. This study unveils the role of ETS-1 as a mediator of inflammation and neointima formation in a model of carotid artery balloon injury and may result in the development of novel strategies in the treatment of vascular injury.

Efficacy of an Olmesartan Medoxomil–Based Treatment Algorithm in Patients Stratified by Age, Race, or Sex

Abstract: Demographic factors are known to influence the prevalence of hypertension, and evidence suggests that they may also influence the response of patients with hypertension to blood pressure (BP)-lowering therapies. To determine the effect of demographic factors on the efficacy and safety of an olmesartan medoxomil (OM)-based treatment regimen, we performed a prespecified subgroup analysis of a 12-week, randomized, placebo-controlled, titrate-to-goal study in patients with hypertension, stratifying patients into treatment groups according to age, sex, or race. After 12 weeks, OM-based therapy significantly reduced BP from baseline in blacks, non-blacks, men, women, and patients younger than 65 or 65 years and older compared with placebo, and enabled 51.9% to 79.5% of patients to achieve a BP goal of <140/90 mm Hg. The differences in BP-lowering efficacy of OM-based therapy between subgroups were not clinically significant, and treatment was generally well tolerated in all groups. This study demonstrates that an OM-based treatment algorithm is an effective and safe option for achieving recommended BP goal in patients with hypertension including blacks, non-blacks, men, women, and patients younger than 65 or 65 years and older.

Have the Renin-Angiotensin-Aldosterone System Perturbations in Cardiovascular Disease Been Exhausted?

Abstract: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure control and volume homeostasis. Inappropriate activation of the RAAS has been implicated in the pathogenesis of hypertension and related cardiovascular disease. Several classes of agents that block RAAS signaling have been shown to be effective antihypertensives and to have cardioprotective and renoprotective properties. Because blockade of the RAAS is incomplete with any of the currently available monotherapies, combinations of these agents have been tested and shown to provide additional clinical benefit in patients with hypertension and various forms of cardiovascular and renal disease.

Comparison of the Antihypertensive Efficacy of Irbesartan//HCTZ and Valsartan//HCTZ Combination Therapy: Impact of Age and Gender

Abstract: This analysis aimed to explore whether low-dose irbesartan/hydrochlorothiazide (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose valsartan/HCTZ in the elderly and across both genders. This is a post-hoc analysis of data from a multicenter, parallel group, open-label, blinded-endpoint study in patients with hypertension uncontrolled with HCTZ monotherapy. The reduction in systolic BP (SBP)/diastolic BP (DBP) and rate of BP control achieved following 8 weeks of treatment with irbesartan/HCTZ 150/12.5 mg or valsartan/HCTZ 80/12.5 mg were analyzed for older (≥65 years) vs. younger (<65 years) patients and for men vs. women. Blood pressure measurements were by home BP monitoring (HBPM). In the age and gender subgroups, both treatments significantly decreased home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically greater with irbesartan/HCTZ compared to valsartan/HCTZ for all subgroups: the difference in DBP was significant for all except the elderly (p < 0.05), and the difference in SBP was significant in the elderly and in men (p < 0.03). In all subgroups, more patients achieved BP control (HBPM ≤135/85 mmHg) in the irbesartan/HCTZ arm (range 45%-58%) than in the valsartan/HCTZ arm (range, 23%-39%; p < 0.02). Both combination therapies were well tolerated and safety parameters were similar in both age and gender subgroups. More patients with mild or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP controlled with irbesartan/HCTZ 150/12.5 mg than with valsartan/HCTZ 80/12.5 mg, irrespective of age or gender.

Blood pressure and migration.

Abstract: Development of urbanized, modern and industrialized societies has generally but not uniformly been associated with increasing blood pressure (BP) and an increased prevalence of hypertension (1–4). ...

Impact of olmesartan on blood pressure, endothelial function, and cardiovascular outcomes.

Abstract: The vascular endothelium, the largest “organ” in the body, synthesizes and releases a wide spectrum of vasoactive substances into the circulation. Endothelial dysfunction links hypertension and other cardiovascular (CV) risk factors that promote the development of atherosclerotic plaque, CV disease, and fatal and nonfatal CV events. Blood pressure (BP) reduction is the most effective way to reduce CV risk in patients with hypertension, but it is unknown whether endothelial dysfunction is a cause or consequence of hypertension. Renin–angiotensin–aldosterone system blockers improve endothelial function and have favorable vascular, metabolic, cardiac, and renoprotective effects that are independent of BP reduction. Olmesartan effectively reduces BP and also has vasoprotective properties, including reductions in endothelial dysfunction and inflammation, prevention of microalbuminuria, and reversal of vascular remodeling. Large-scale, long-term studies are needed to confirm that olmesartan has vasoprotective effects that are independent of BP control and to determine whether these pleiotropic effects translate into improved CV disease outcomes.

Blood pressure variability: Emerging role in risk assessment and therapeutics

Abstract: of future research. Commentary by Dr. Tony Heagerty critically reviewed the implications and limitations of BP variability assessment for future guidelines and clinical practice and outlined recommendations for future research. Dr. Rothwell drew on his experience in the Stroke Prevention Research Unit at Oxford to emphasize the striking relationship between BP variability and stroke. He showed that within individual visit-to-visit variability in systolic BP (SBP) is increased in cohorts at high risk of stroke, i.e., those with established cerebrovascular disease, or previous transient ischemic attack (TIA) or stroke, is reproducible within individuals over time, and is a powerful predictor of stroke independently of mean SBP (3,10–15). Evidence from randomized controlled trials of antihypertensive treatment and of secondary stroke prevention, including the Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) (16), the Medical Research Council (MRC) trial of the treatment of hypertension in older adults (17 ) and the UK-TIA trial (18 ) support the thesis that, independent of mean systolic BP, treatments that effect the greatest reduction in BP variability are associated with the greatest reductions in risk. ASCOT-BPLA reported that a calcium channel blocker (CCB, amlodipine) based regimen was more effective in preventing stroke and coronary events than expected, based on change in mean BP, and more effective compared to a beta blocker (BB, atenolol) based regimen; and that this differential effect was independent of changes in other measured vascular risk factors during follow-up (16,19). Within individual visit-to-visit variability in clinic SBP, diastolic BP (DBP) and pulse pressure (PP) were expressed as the standard deviation (SD) and coeffi cient of variation Blood Pressure. 2010; 19: 209–211

Angiotensin receptor blockers and cancer - Relationship dismissed by VALUE data while waiting for EMA and FDA reports.

Abstract: As editors of Blood Pressure , a hypertension research journal, we feel strongly obligated to point out a fundamental shortcoming in a recently published metaanalysis of cancer rates in patients treated with angiotensin receptor blockers (ARBs). The online publication of the June 14 issue of Lancet Oncology contains a paper by Sipahi et al. entitled “ Angiotensin receptor blockade (ARB) and risk of cancer; meta-analysis of randomized controlled trials ” (1). A major conclusion of the report is based on Figure 4B, labeled “ Cancer in patients without a background of treatment with angiotensin converting enzyme inhibitors ” , which contains these data on cases of incident cancer as a proportion of total patient numbers: ARB, n 1360/16,497 and control, n 1262/16,527, representing a difference between the two groups of 98 patients with cancer. Relying on this narrow difference, the authors made a claim, supported by an uncritical editorial (2) in the same issue of the Journal, of a possible link between ARB use and cancer. The VALUE Trial (3), which compared outcomes with an ARB and a calcium-channel blocker in hypertensive patients at high cardiovascular risk, is quoted by the report of Sipahi et al. (1), but it is erroneously stated that VALUE did not collect cancer information and therefore was not included in the meta-analysis. In reality, cancer data were collected and included in VALUE ’ s formal database, completed in March 2004. Every case of cancer was described with a specifi c diagnosis. In VALUE, there were a total of 510/7649 cancer cases reported with the ARB valsartan (6.7%) vs 591/7596 cases reported with the calcium-channel blocker amlodipine (7.8%). In that large clinical trial, with 15,245 patients followed for several years, this fi nding obviously argues

A STITCH saves time and lowers blood pressure.

Abstract: Blood pressure control remains suboptimal despite the availability of effective antihypertensive drugs and wellpublicized practice guidelines. The complexity of treatment guidelines and the multidrug regimens that are needed to achieve blood pressure control in most hypertensive patients are major contributors to suboptimal blood pressure control. The Simplified Treatment Intervention To Control Hypertension (STITCH) is a simple, step-care–based algorithm for the pharmacologic management of hypertension, which was designed to improve blood pressure control by removing the obstacle of complexity.

Intensive treatment with combination amlodipine/valsartan provides greater efficacy vs moderate treatment for hypertensive patients uncontrolled on arb monotherapy: the extra study: pp.5.208

Abstract: Objective: Many ARB monotherapy patients (pts) will need >=2 agents to control BP. We investigated whether initiating intensive treatment with combination amlodipine/valsartan (A/V 5/320 to 10/320 mg) was superior to moderate treatment with A/V 5/160 mg in pts previously uncontrolled on ARB monotherapy. Methods: In this 12-wk study, pts aged >=18 years on ARB (other than V) for >=28 days (with treatment-naïve pts or those not controlled on agents other than an ARB treated with open-label olmesartan 20 or 40 mg, respectively, for 28 days) and with uncontrolled MSSBP (>=150–<200 mmHg) were randomized to A/V 5/320 (n=369) or A/V 5/160 mg (n=359); at Wk 2, the dose was increased to 10/320 mg in the intensive arm. HCTZ 12.5 mg was added to both arms at Wk 4. Optional up-titration with HCTZ 12.5 mg at Wk 8 was allowed if MSSBP >140 mmHg. Results: At baseline, mean office sitting BP was similar in the 2 treatment arms (table). Intensive treatment provided significantly greater BP reductions vs moderate treatment from Wk 4 (primary endpoint) to Wk 12. BP goal (<140/90 mmHg) was achieved in significantly more pts in the intensive arm at all weeks vs the moderate arm. Both treatments were generally well tolerated. AEs were reported by a similar percentage of pts in both groups (36.3% intensive, 37.6% moderate); the most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). Conclusion: Thus, initiating treatment with an intensive dose of A/V 5/320 to 10/320 mg provides significantly greater BP lowering with an excellent safety profile vs moderate treatment in hypertensive pts unresponsive to ARB monotherapy. Figure 1. No caption available.

Intensive Dose Of Combination Amlodipine/valsartan Provides Improved 24-h Bp Response Compared To Moderate Dose In Hypertensive Patients Uncontrolled On Arb Monotherapy: Pp.5.211

Abstract: Objective: To evaluate the efficacy of initiating treatment with an intensive dose of amlodipine/valsartan (A/V 5/320 to 10/320 mg) vs a moderate dose of A/V (5/160 mg) in hypertensive patients (pts) unresponsive to ARB monotherapy using ambulatory blood pressure monitoring (ABPM). Methods: This analysis presents data in a subset of pts (n=80) in a 12-wk study. Pts aged >=18 years on ARB (other than V) for >=28 d (with treatment-naive pts or those not controlled on agents other than an ARB treated with olmesartan 20 or 40 mg, respectively, for 28 d) and with uncontrolled MSSBP (>=150– 140 mmHg. ABPM was compared with home and clinic BP. Results: As with clinic BP, intensive treatment provided significant 24 h ABP reductions vs moderate treatment (table). Numerically greater home BP reductions were observed with intensive vs moderate treatment (p=NS). In the overall study, AEs were reported by a similar percentage of pts in both groups (36.3% intensive, 37.6% moderate); the most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). Conclusion: ABPM results support an intensive treatment approach in this pt population.

Intensive treatment with combination amlodipine/valsartan vs moderate therapy for hypertensive patients with diabetes or ckd uncontrolled on arb monotherapy: pp.17.149

Abstract: Objective: Hypertensive patients (pts) with diabetes (D) or CKD are at high risk and require > = 2 agents for BP control. In a 12-wk study of hypertensive pts unresponsive to ARB monotherapy, initial treatment with intensive dose of amlodipine/valsartan (A/V 5/320 to 10/320 mg) provided significantly greater BP efficacy than moderate dose (5/160 mg). Here we present data in D pts, stage-2 CKD pts (eGFR > = 60–<90 mL/min/1.73 m2), and stage-3 CKD pts (eGFR > = 30–<60 mL/min/1.73 m2). Methods: Pts aged > = 18 years on ARB (other than V) for > = 28 d (with treatment-naïve pts or pts not controlled on agents other than an ARB treated with olmesartan 20 or 40 mg, respectively, for 28 d) and with uncontrolled MSSBP (> = 150–<200 mmHg) were randomized to A/V 5/320 or 5/160 mg; increased to 10/320 mg in the intensive arm at Wk 2 and addition of HCTZ 12.5 mg to both arms at Wk 4; optional up-titration with HCTZ 12.5 mg at Wk 8 was allowed if MSSBP >140 mmHg. Results: Intensive treatment provided significant BP reductions vs moderate treatment by Wk 4 in D and stage 2 CKD pts (table). Overall, percent AEs were similar in both groups (36.3% intensive, 37.6% moderate); most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). Figure 1. No caption available. Conclusion: Initiating treatment of hypertensive diabetic or stage 2 CKD pts with an intensive dose of A/V provided greater antihypertensive efficacy than moderate treatment.

Greater Efficacy With Amlodipine/valsartan Combination Intensive Vs Moderate Treatment For Hypertensive Patients With Cardiometabolic Syndrome Uncontrolled On Arb Monotherapy: Pp.34.432

Abstract: Hypertensive patients (pts) with cardiometabolic syndrome (MetS) are at high-risk and require >=2 agents for BP control. Previously in a 12-week study, initial treatment with an intensive dose of amlodipine/valsartan (A/V 5/320 to 10/320 mg) provided significantly greater BP lowering and control than moderate dose (5/160 mg) in hypertensive patients (pts) unresponsive to ARB monotherapy. Here we present the data in a subset of MetS pts by ATP III criteria. Pts aged >=18 years on ARB (other than V) for >=28 days (with treatment-naive pts or those not controlled on agents other than ARB treated with open-label olmesartan 20 or 40 mg, respectively, for 28 days) and with uncontrolled mean sitting systolic BP (MSSBP; >=150- 140 mmHg. In the subset of 345 MetS pts (mean age 56 years, 51% women), baseline MSSBP was similar between groups (table). Intensive treatment provided significantly greater BP reductions vs moderate treatment from Week 4 (primary endpoint) to Week 12. At Weeks 4 and 8, significantly more pts in the intensive vs moderate arm achieved BP goal (<140/90 mmHg). In the overall study, percent adverse events (AEs) were similar in both groups (36.3% intensive, 37.6% moderate); most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). Initiating treatment in hypertensive MetS pts with an intensive dose of A/V provided significantly greater antihypertensive efficacy than moderate treatment.

Triple combination therapy with amlodipine/valsartan/hctz at maximal doses is safe and effective for hypertensive patients uncontrolled on arb monotherapy: the extra study: pp.5.216

Abstract: Objective: To compare the BP efficacy of combination amlodipine/valsartan (A/V) intensive dose (10/320 mg) vs moderate dose (5/160 mg), with addition of HCTZ, in pts uncontrolled on ARB monotherapy. Methods: Pts aged >=18 years on ARB (other than V) for >=28 d (treatment-naïve pts or those uncontrolled on agents other than an ARB treated with olmesartan 20 or 40 mg, respectively, for 28 d) and with uncontrolled MSSBP (>=150–<200 mmHg) were randomized to A/V 5/320 (n=369) or A/V 5/160 mg (n=359); increased to 10/320 mg in the intensive arm at Wk 2. HCTZ 12.5 mg was added to both arms at Wk 4. Optional up-titration with HCTZ 12.5 mg at Wk 8 was allowed if MSSBP >140 mmHg. Results: 127 pts (35%) in the intensive arm (mean, 27.6 d) and 170 (48%) in the moderate arm (mean, 28.2 d) received optional HCTZ 12.5 mg with A/V/HCTZ 10/320/25 or 5/160/25 mg. For pts up-titrated with full HCTZ dose, MSSBP at wk 8 decreased from 167.2 mmHg (baseline) to 144.5 mmHg in the intensive group and from 165.4 mmHg to 149.0 mmHg in the moderate arm. Additional reductions of 4.5 mmHg in the intensive arm and 5.8 mmHg in the moderate arm (figure) were observed from Wk 8 to Wk 12 only in pts receiving full-dose HCTZ. Overall, AEs were similar in both groups (36.3% intensive, 37.6% moderate); most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). In pts receiving full HCTZ dose, AEs at Wk 8 were 6.3% vs 3.5% (Wk 12: 8.7% vs 4.1%) for peripheral edema and 3.1% vs 0% (Wk 12: 3.9% vs 1.8%) for dizziness. A substantial proportion of pts in both treatment arms required triple therapy with the full HCTZ dose (25 mg). Conclusion: Use of triple combination A/V/HCTZ with maximal dose of 10/320/25 mg is safe for pts who are able to up-titrate and results in additional BP reduction. Figure 1. No caption available.

Cardiovascular risks in HIV patients.

Abstract: In HIV patients, the increased use of highly active antiretroviral therapy (HAART) has resulted in effective suppression of virus replication, reduction of opportunistic infections and malignancies...

Blood Pressure celebrates 20 years of dedication to Nordic hypertension research.

Abstract: Lennart Hansson, MD, PhD, professor at the University of Uppsala and founding editor of Blood Pressure ( † 2002). Hypertension research in the Nordic area of Europe has longstanding traditions. Tigerstedt and Bergman, von Euler, Hood, Folkow, Hilden, Storm Mathiesen and Humerfeldt were some of the pioneers until around 1960, when Lund-Johansen, Giese, Berglund, Lithell and later Omvik, Ibsen, Eide, Fyhrquist, Lindholm and Hansson took over the leadership. Lennart Hansson , who passed away in 2002 from cancer, founded Blood Pressure in 1990 in a response to the escalating numbers of hypertension studies in the Nordic countries and the need for improved publications access. In the year 2000, somewhat by coincidence, Lennart organized the 10 th European Meeting on Hypertension in his home town of G ö teborg, Sweden and simultaneously issued the 10-year jubilee issue of Blood Pressure in honor of Nordic hypertension research. An important part of Nordic hypertension research has long been the design and performance of large randomized outcomes trials. The Oslo Study (1) came out in parallel with a dozen or so other randomized controlled trials in the United Kingdom, Australia and United States of America about 30 years ago. It showed major benefi ts of drug treatment in preventing stroke and heart disease in subjects with mild to severe hypertension. Later trials, including the Nordic MAPPY and HAPPY studies, found diuretics and beta-blockers equally effective in preventing these outcomes. More recently, trials initiated by Lennart Hansson and published in Blood Pressure have dominated the literature and discussions at congresses. The most important of these studies, now remembered by their acronyms, STOP, HOT, STOP 2, CAPPP and NOR-