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BACKGROUND: The Corona Virus 19 (COVID-19) infection is associated with worse outcomes in blacks, although the mechanisms are unclear. We sought to determine the significance of black race, pre-existing cardiovascular disease (pCVD), and acute kidney injury (AKI) on cardiopulmonary outcomes and in-hospital mortality of COVID-19 patients. METHODS: We conducted a retrospective cohort study of blacks with/without pCVD and with/without in-hospital AKI, hospitalized within Grady Memorial Hospital in Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. The primary outcome was a composite of in-hospital cardiac events. RESULTS: Of the 293 patients hospitalized with COVID-19 in this study, 71 were excluded from the primary analysis (for race/ethnicity other than black non-Hispanic). Of the 222 hospitalized COVID-19 patients included in our analyses, 41.4% were female, 78.8% had pCVD, and 30.6% developed AKI during the admission. In multivariable analyses, pCVD (OR 4.7, 95% CI 1.5-14.8, P=0.008) and AKI (OR 2.7, 95% CI 1.3-5.5, P=0.006) were associated with increased odds of in-hospital cardiac events. AKI was associated with increased odds of in-hospital mortality (OR 8.9, 95% CI 3.3-23.9, P

Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment.

Cardiovascular disease (CVD) burden is several-fold higher in patients with chronic kidney disease (CKD). Although statins have been shown to provide significant CVD benefits in both the general population and patients with CKD, this has not translated into survival advantage in patients with advanced CKD or on dialysis. It has been reported that CVD risk continues to escalate as CKD progresses to end-stage kidney disease (ESKD); however, the CVD risk reduction by statins appears to decline as patients’ progress from the early to later stages of CKD. Statins have also been associated with a higher incidence of stroke in ESKD patients. Thus, the CVD benefits of statins in ESKD remain questionable.

Background— Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. Methods and Results— We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, –4.2 [–4.9, –3.5] mg/dL and –3.5 [–4.2, –2.7] mg/dL at 12 and 24 weeks, respectively, both P P =0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P =0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P =0.36). Conclusions— In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00987415.

Introduction Based upon the findings of the African-American Heart Failure Trial, the US Food and Drug Administration approved the fixed-dose combination of isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HYD) (FDC-ISDN/HYD) as a new drug for treatment of heart failure (HF) in self-identified African Americans. According to the FDA, FDC-ISDN/HYD has no therapeutic equivalent. However, off-label combinations of the separate generic drugs ISDN and HYD (OLC-ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are routinely substituted without any supporting outcome data. We conducted an exploratory retrospective propensity-matched cohort study using Medicare data to determine whether a survival difference exists between these treatments in medication-adherent patients. Methods Black Medicare beneficiaries with HF were matched with Medicare Part D data to identify patients with prescriptions to FDC-ISDN/HYD or the off-label combinations. Only patients with 1-year adherence levels ≥80% were included in the analysis. Propensity-matched scoring created two sets of matched cohort pairs on a 1:1 basis, each set comparing FDC-ISDN/HYD with one of the off-label combinations. Kaplan-Meier (KM) survival curves with the log-rank test were then calculated for each pair for the year of medication adherence. Results The analysis population was relatively older (77 years) and mainly female (66.7%), with a high burden of comorbid disease. The KM estimates of 1-year survival were 87.9% (95% CI 85.6–89.9%) and 83.0% (95% CI 80.3–85.3%) (log rank p = 0.0024), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISDN+HYD (n = 886 in each group) and 88.2% (95% CI 85.9–90.2%) and 84.8% (95% CI 82.2–87.0%) (log rank p = 0.0320), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISMN+HYD (n = 868 in each group). Conclusion The 1-year survival advantage for FDC-ISDN/HYD compared with off-label combinations in adherent black Medicare beneficiaries with HF suggests a genuine difference between these medications and warrants prospective investigation.

Background: Self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) have been proven effective in improving hemoglobin A1c (HbA1c) and in reducing hypoglycemia in patients with type 1 diabetes mellitus (T1DM). It is not clear, however, if CGM provides further efficacy and safety benefits beyond SMBG in the management of T1DM. Methods: MEDLINE (1966–November 2009), COCHRANE REGISTRY (all years), and EMBASE (1980–November 2009), and article bibliographies were searched for randomized controlled trials (RCTs) investigating the use of CGM in patients with T1DM, with clinical outcomes, including HbA1c and hypoglycemia and/or hyperglycemia. Results: Fourteen RCTs met eligibility criteria [n = 1188 patients, 97.4% with T1DM, age 29.0 ± 14.3 years, diabetes duration 11.7 ± 7.0 years, and baseline HbA1c 8.3 ± 0.8% (mean ± standard deviation)]. Compared with SMBG, the use of CGM was associated with a greater reduction in HbA1c [-0.3% (confidence interval: 0.4, -0.2), p < .0001]. The number of hypoglycemic events was not significantly different between the CGM and SMBG groups (0.52 ± 0.52 versus 0.52 ± 0.63 events/day, p = .5), but duration of hypoglycemia was shorter for the CGM group (75 ± 39 versus 89 ± 19 min/day), with an incremental reduction of hypoglycemia duration of -15.2 min/day, p < .0001. Continuous glucose monitoring also resulted in a shorter duration of hyperglycemia than SMBG (172 ± 125 versus 217 ± 152 min/day, p = .04). Conclusions: The use of CGM is associated with improvement in metabolic control in T1DM, with significant short- and long-term reductions in HbA1c and reduction in the duration of periods of hypoglycemia and hyperglycemia versus SMBG.

Ambulatory blood pressure monitoring (ABPM) has greater predictive value than office blood pressure (BP) with respect to hypertension-related target-organ damage and morbidity. ABPM in a subset of 80 patients from the Exforge Target Achievement trial (N=728) was used to compare the efficacy of intensive-treatment and moderate-treatment regimens of amlodipine/valsartan, and to determine whether treatment differences could be better assessed with ABPM than with office or home BP. Home BP was measured on the morning of clinic visits to minimize differences that timing might have on home versus office BP measures.A 12-week randomized, double-blind study in which hypertensive patients earlier uncontrolled (mean sitting systolic BP≥150 and200 mmHg) on angiotensin receptor blocker monotherapy (other than valsartan) after 28 days or more (N=728) were randomized to amlodipine/valsartan treatment [10/320 mg (intensive) or 5/160 mg (moderate)]. Treatment-naive patients (in previous 28 days) or patients who failed on a nonangiotensin receptor blocker agent underwent a 28-day run-in period with a 20-mg or 40-mg dose of olmesartan, respectively.Significantly greater 24-h ABP reductions from baseline to week 4 (primary time point) were observed with intensive versus moderate treatment (least-square mean systolic/diastolic BP reduction of -16.2/-10.1 vs. -9.5/-6.5 mmHg; P=0.0024/P=0.010 for least-square mean difference). Similarly, a significantly greater proportion of patients receiving an intensive treatment achieved ambulatory BP goal (130/80 mmHg) at week 4 than did those receiving a moderate treatment (P=0.040). Treatment-group differences did not reach statistical significance for these end points when measured by office and home BP.In this first randomized trial evaluating the effects of intensive versus moderate dosing of the combination of amlodipine/valsartan, our data suggest that ABPM was a better method for assessing between-treatment differences than clinic or home BP recordings, although measurement of home BP as a single recording was a limitation of our trial.

Many angiotensin receptor blocker (ARB) monotherapy patients need at least two agents to control blood pressure (BP). We investigated whether initiating intensive treatment with combination amlodipine/valsartan was superior to moderate treatment with amlodipine/valsartan in patients previously uncontrolled on ARB monotherapy.In this 12-week study, patients aged at least 18 years on ARB (other than valsartan) for at least 28 days (with treatment-naïve patients 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 mean sitting systolic blood pressure (MSSBP; ≥ 150-200 mmHg) were randomized to amlodipine/valsartan 5/320 mg (n = 369) or 5/160 mg (n = 359). At week 2, the dose was increased to 10/320 mg in the intensive arm. Hydrochlorothiazide 12.5 mg was added to both arms at week 4. Optional up-titration with hydrochlorothiazide 12.5 mg at week 8 was allowed if MSSBP was more than 140 mmHg.At baseline, mean office sitting BP was comparable in the intensive (163.9/95.5 mmHg) and moderate (163.3/95.0 mmHg) groups. Intensive treatment provided greater BP reductions versus moderate treatment (P0.05) from week 4 (-23.0/-10.4 versus -19.2/-8.7 mmHg; primary endpoint) to week 12 (-29.0/-14.8 versus -25.3/-12.3 mmHg). Adverse events were reported by a similar percentage of patients in both groups (36.3% intensive, 37.6% moderate); peripheral edema was more common with intensive versus moderate treatment (8.7 versus 4.5%; P = 0.025).Initiating treatment with an intensive dose of amlodipine/valsartan provides significantly greater BP lowering versus moderate treatment in hypertensive patients unresponsive to ARB monotherapy. Both treatment regimens were generally well tolerated based on adverse event reports, but the lack of routine laboratory testing after screening limits conclusions on tolerability.

Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear.To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured.At week 16, clinic blood pressure reductions were similar (P0.05) in both groups. Fasting and 2-h glucose levels increased (P0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion.The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.

Genetic heterogeneity at the endothelial nitric oxide synthase (NOS3) locus influences heart failure outcomes. The prevalence of NOS3 variants differs in black and white cohorts, but the impact of these differences is unknown.Subjects (n = 352) in the Genetic Risk Assessment of Heart Failure (GRAHF) substudy of the African-American Heart Failure Trial were genotyped for NOS3 polymorphisms: -786 T/C promoter, intron 4a/4b, and Glu298Asp and allele frequencies and compared with a white heart failure cohort. The effect of treatment with fixed-dose combination of isosorbide dinitrates and hydralazine (FDC I/H) on event-free survival and composite score (CS) of survival, hospitalization, and quality of life (QoL) was analyzed within genotype subsets. In GRAHF, NOS3 genotype frequencies differed from the white cohort (P.001). The -786 T allele was associated with lower left ventricular ejection fraction (LVEF) (P = .01), whereas the intron 4a allele was linked to lower diastolic blood pressure and higher LVEF (P = .03). Only the Glu298Asp polymorphism influenced treatment outcome; therapy with FDC I/H improved CS (P = .046) and QoL (P = .03) in the Glu298Glu subset only.In black subjects with heart failure, NOS3 genotype influences blood pressure and left ventricular remodeling. The impact of genetic heterogeneity on treatment with FDC I/H requires further study.

The basis for the treatment of hypertension in women has evolved in step with the inclusion of women in studies of treatment in hypertension. Recent outcome trials comparing angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcium antagonists with diuretics and beta-blockers in older, high-risk patients have generally shown similar benefits for women and men. The current evidence therefore indicates that sex should not play a role in decisions about whether to treat hypertension or about the choice of agents.

Background Previous studies suggest that patients with sickle cell anemia (SCA) have an increased risk of sudden cardiac death; however, its etiology and mechanism are not well defined. Left ventricular hypertrophy (LVH), ventricular tachycardia (VT) and poor left ventricular systolic function are known risk factors for sudden cardiac death. An abnormal microvolt T-wave alter-nans (TWA) test is also a predictor of sudden cardiac death risk, but it has not been applied to this patient population. Methods We performed a 12-lead electrocardiogram, 24 hour Holter monitor, two-dimensional echocardiogram, nuclear stress test and microvolt TWA test to determine whether markers of sudden cardiac death could be identified. Results Twenty-six patients were evaluated with a mean age of 40 ± 12 years. The two-dimensional echocardiogram revealed a normal ejection fraction in 23 patients and LVH in 17 (65%), whereas hypertension was noted in only five (19%). Microvolt TWA testing was abnormal in six of 22 patients (27%). Holter monitor revealed VT in two patients. Among the clinical variables tested, only LVH was predictive of an abnormal TWA test. The sensitivity, specificity, positive and negative predictive value of LVH for and abnormal TWA test was 100, 56, 46 and 100%. Conclusion LVH was common in patients with SCA and dis-proportional to the number of patients with hypertension. Microvolt TWA tests were abnormal in 27% of patients; however, LVH was the only clinical variable that predicted an abnormal TWA test. Risk stratification of SCA patients may require echocardiographic detection of LVH and an abnormal TWA test due to the high negative predictive value. The significance of an abnormal TWA test should be further evaluated in a large study, with a longer follow-up period.

Cardiovascular disease is the leading cause of death in the United States, accounting for approximately 60% of total mortality in 2002. There is evidence that race and ethnicity is a risk factor for atherothrombotic events. Blacks have a greater risk of complications from coronary heart disease and unstable angina, with a higher coronary heart disease death rate compared with whites. The risk of ischemic stroke is 2-4 times higher among blacks compared with whites, whereas the risk of peripheral arterial disease is highest among non-Hispanic blacks. Additionally, Asian-Pacific Islander ethnicity is an independent risk factor for bleeding, even though this ethnic group receives less antithrombotic therapy compared with whites. The increased risk of events in these patient populations may have its basis in racial and ethnic differences in the pathobiology of atherosclerosis. Some racial and ethnic populations are also inadequately prescribed antiplatelet therapy despite their higher risk. Although this difference in therapy is hard to explain, it is becoming clear that factors other than socioeconomic status or clinical presentation are influencing racial differences in physician provisions of therapy. Antiplatelet therapy, including aspirin and clopidogrel, is an important component of risk reduction strategies, and there are few data to suggest racial or ethnic variations in drug efficacies. Thus, understanding and overcoming race and ethnicity-related treatment disparities should lead to significant clinical improvements in these under-served populations.

Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >or= 4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P

Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment.

Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment.

The prevalence of hypertension dictates that blood pressure must be managed effectively in primary care. The American Society of Hypertension (ASH) regional chapters and clinical hypertension specialists represent a positive response by ASH to the growing problems of hypertension and metabolic syndrome-related risks and disease. To have a significant public health effect, the impact of clinical hypertension specialists must be leveraged. Key activities in the community include educating other providers locally, delivering care for complex referral patients, and fostering growth of a practice network with a central database in collaboration with academic partners. The database supports practice audit and feedback reports to enhance quality improvement, identify continuing medical education topics, and facilitate clinical trials to test new therapeutic and best-practice approaches to risk factor management. The ASH regional chapters serve as a forum for community and academic hypertension specialists to collaborate with like-minded individuals and organizations. The collaboration among the ASH Carolinas-Georgia chapter, the Hypertension Initiative, and the Community Physicians' Network provides a model for other ASH chapters and health delivery groups to partner in delivering continuing medical education programs focused on cardiovascular risk factor management, recruiting practices into the network, and developing and maintaining a centralized patient database. Evidence suggests that this collaboration is facilitating application of evidence-based medicine and risk factor control.

Data from well designed randomized trials have proven the effectiveness of an intensive approach to hypertension management in reducing morbidity and mortality. Based on these data, guidelines recommend a blood pressure goal of

Clinical and metabolic complications of late referral (LR) for dialysis therapy have been well documented, but there is a paucity of data on its socioeconomic implications. This study examines the role of lifestyle and socioeconomic status on referral pattern.During a 4-year period (1999 to 2002), we retrospectively reviewed records of all patients who initiated dialysis therapy at an urban tertiary-care center. Patients were classified into 3 categories according to the interval between first contact with a nephrologist and initiation of dialysis therapy: contact time of 3 months or longer indicates early referral (ER); 1 to less than 3 months, LR; and less than 1 month, ultralate referral (ULR).Of 460 patients (97% African Americans, 3% Hispanics), 212 patients (46%) were ULR, 168 patients (37%) were LR, and 80 patients (17%) were ER. Compared with ER and LR patients, those with ULR had significantly (P0.0001) lower hematocrits (23% versus 29% and 27%), serum albumin levels (3.1 versus 3.3 and 3.2 g/dL [31 versus 33 and 32 g/L]), and glomerular filtration rates (5 versus 8 and 7 mL/min/1.73 m2 [0.08 versus 0.13 and 0.12 mL/s/1.73 m2]), but greater rates of temporary dialysis catheter use (92% versus 39% and 70%) and mortality (40% versus 15% and 26%, respectively). Logistic regression analysis showed an association between mortality and homelessness (odds ratio, 3.8; P0.0001), polysubstance abuse (odds ratio, 2.3; P = 0.013), and alcoholism (odds ratio, 2.2; P = 0.009). Alcoholics (odds ratio, 2.5; P = 0.03), substance abusers (odds ratio, 5.5; P = 0.001), and the homeless/unemployed (odds ratio, 6.0; P = 0.004) were more likely to present as ULR cases. Patient-provided explanations for LR and ULR were denial (45%), unawareness of the presence of chronic kidney disease (30%), and economic difficulties (25%). Denial was more prevalent in LR (52%; P = 0.003) and ULR cases (39%; P = 0.003).Poor socioeconomic status is a major contributor to delayed referral. More efforts need to be directed at patient and physician chronic kidney disease educational awareness and improved health care access for inner-city and minority populations.

Background: The role of eNOS gene polymorphisms on plasma nitrite or nitrate (NOx) level, endothelial function, and blood pressure (BP) remains unclear. Methods: We estimated the relationship of eNOS polymorphisms (the T 786 C in the 5-flanking promoter region, T 786 C; 27-bp repeat in intron 4, eNOS4; and Glu298Asp in exon 7, G894T) with plasma NOx level, brachial endothelial function assessed by ultrasound measure of brachial artery flow-mediated dilation (FMD), and BP in 60 healthy African Americans, 30 men and 30 women aged 18 to 73 years. Results: Among them, 73.1%, 23.9%, and 3.0% carried TT, TC, and CC of T 786 C, respectively, 14.5%, 27.5%, 53.6%, and 1.4% carried aa, ab, bb, and bc of eNOS4 polymorphism, respectively, and 70.4%, 23.9%, and 5.6% carried GG, GT, and TT of G894T, respectively. G894T and eNOS4 were observed in linkage disequilibrium. Mean values of age, plasma NOx, FMD, systolic and diastolic BPs were not significantly different (P .05) by eNOS polymorphisms. Plasma NOx level was found to be associated with systolic BP (r 0.51, P .03), and diastolic BP (r 0.41, P .08), but not with FMD, in individuals with “a” allele of eNOS4 polymorphism after adjustment for age, body mass index, serum glucose, and smoking status. Conclusions: We reveal a positive association between plasma NOx level and BP in normotensive African Americans who carry the “a” allele of eNOS4. Because the frequency of the rare allele “a” is significantly higher in African Americans than in other ethnic groups, this finding may provide a clue to understanding the genetic susceptibility to hypertension in African Americans. Am J Hypertens 2004;17:560 ‐567 © 2004 American Journal of Hypertension, Ltd.

Background African Americans have greater precordial QRS voltages than whites, with concomitant higher prevalences of electrocardiographic (ECG) left ventricular hypertrophy (LVH) and lower specificity of ECG LVH criteria for the identification of anatomic hypertrophy. However, the high mortality associated with LVH in African American patients makes more accurate ECG detection of LVH in these patients a clinical priority. Methods Electrocardiograms and echocardiograms were obtained at study baseline in 120 African American and 751 white hypertensive patients enrolled in the Losartan Intervention For Endpoint (LIFE) echocardiographic substudy. The ECG LVH was determined using Sokolow-Lyon, 12-lead sum, and Cornell voltage criteria. Echocardiographic LVH was defined by LV mass indexed to height 2.7 >46.7 g/m 2.7 in women and >49.1 g/m 2.7 in men. Results After adjusting for ethnic differences in LV mass, body mass index, sex, and prevalence of diabetes, mean Sokolow-Lyon and 12-lead sum of voltage were significantly higher, but Cornell voltage was lower, in African Americans than in whites. As a consequence of these differences, when identical partition values were used in both ethnic groups, Sokolow-Lyon and 12-lead voltage criteria had lower specificity in African Americans than whites (44% v 69%, P = .007 and 44% v 59%, P = .10) but had greater sensitivity in African Americans (51% v 27%, P v 45%, P = .003). In contrast, Cornell voltage specificity was higher (78% v 62%, P = .09) but sensitivity was slightly lower (49% v 57%, P = 0.16) in African Americans. However, when overall test performance was compared using receiver operating curve analyses that were independent of partition value selection, ethnic differences in test performance disappeared, with no differences in accuracy of any of the ECG voltage criteria for the identification of LVH between African American and white hypertensive individuals. Conclusions When standard, non–ethnicity-specific thresholds for the identification of LVH are used, Sokolow-Lyon and 12-lead voltage overestimate and Cornell voltage underestimates the presence and severity of LVH in African American relative to white individuals. However, these apparent ethnic differences in test performance disappear when ethnic differences in the distribution of ECG LVH criteria are taken into account. These findings demonstrate that ethnicity-specific ECG criteria can equalize detection of anatomic LVH in African American and white patients.

Heart failure (HF) remains a significant cardiovascular problem, with increasing incidence and prevalence rates: Adult Americans over 40 years of age have a 20 % lifetime risk of developing heart failure. Approximately five million people in the USA have HF, and over 650,000 new cases of HF are diagnosed each year. HF incidence increases with age: from 20 per 1,000 among individuals 65–69 years of age to greater than 80 per 1,000 for individuals who are over 85 years of age.

Background The presence of an abnormal late-peaking left ventricular velocity contour, detected by Doppler echocardiography, has been reported in patients with hypertrophic cardiomyopathy, left ventricular hypertrophy, and aortic stenosis. Methods and Results To evaluate the clinical and prognostic significance of this characteristic Doppler finding, we studied a group of patients ( n = 57) with isolated AS undergoing aortic valve replacement. Patients were divided into two groups according to the presence ( n = 28) or absence ( n = 29) of a hypertrophic late-peaking left ventricular velocity pattern. There were no differences between the groups with respect to age, sex, and presence of coronary artery disease. Peak preoperative aortic valve gradients were similar in both groups (70 vs. 67 mm Hg; p = not significant). The postoperative course of patients with abnormal late-peaking ventricular velocity contour was complicated by a higher incidence of arrhythmias (80% vs. 38%; p = 0.0002). Hypotension and the use of inotropic support were significantly more common in the group with abnormal late-peaking ventricular velocity contour (79% vs. 24%; p = 0.0001 and 76% vs. 26%; p = 0.0001, respectively). Hemodynamically, patients with a late-peaking velocity pattern exhibited a higher pulmonary diastolic pressure (16 ± 3 vs 12 ± 2 mm Hg; p = 0.0003), wedge pressure (12 ± 4 vs 10 ± 2; p p = 0.0001) and lower cardiac index (2.4 ± 0.3 vs 2.9 ± 0.4; p = 0.0001). Conclusions An abnormal late-peaking ventricular velocity contour pattern appears to be a high risk marker for postoperative complications in patients undergoing aortic valve replacement. Routine Doppler evaluation in patients undergoing valve replacement for AS may therefore identify these patients. (Am Heart J 1998;136:71-7.)

Variations in reported sensitivity of myocardial perfusion scans or wall motion abnormalities during pharmacologic stress with intravenous adenosine and dipyridamole may be caused by differences in myocardial oxygen demand or myocardial blood flow redistribution induced by each agent. To investigate the physiologic correlates of functional abnormalities during pharmacologic stress testing, regional myocardial blood flow (radiolabeled microsphere technique) and left ventricular segmental wall thickening (quantitative two-dimensional echocardiography) were measured in 9 dogs with an open chest model of critical stenosis of the left circumflex coronary artery. Data were obtained at baseline and peak drug infusion for intravenous adenosine (0.42 mg/kg over a 3-minute period) and for intravenous dipyridamole (0.56 mg/kg over a 4-minute period). Adenosine and dipyridamole induced regional flow abnormality in 7 (77%) of 9 dogs. Myocardial segments with decreased endocardial/epicardial flow ratio were similar for both agents (2.9 +/- 1.8 vs 2.7 +/- 1.3, p = [NS]). Segments with myocardial flow heterogeneity (ratio of endocardial flow to control left anterior descending/left circumflex endocardial flow) were similar for both agents (2.7 +/- 0.9 vs 2.3 +/- 1.0, p = NS). Adenosine-induced wall thickening abnormality (77% vs 55% with dipyridamole) correlated with regional flow abnormality. Significantly lower mean arterial pressure (53 +/- 1.7 mm Hg vs 64 +/- 1.9 mm Hg, p < 0.01) and more prolonged drug effect (18 +/- 6.4 min vs 3 +/- 1.4 min, p < 0.001) were seen for dipyridamole compared with adenosine. Adenosine induces regional flow abnormality similar to dipyridamole but with less hemodynamic perturbation, and adenosine-induced wall thickening abnormality more closely parallels regional flow abnormality.

Association between angiographic coronary artery disease and cardiac troponin T levels has been observed in patients with normal kidney function; however, this association remains unsettled in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). Over a 12-month period we retrospectively reviewed coronary angiograms (CAs) performed in 194 hospitalized patients with presumed acute myocardial injury. About 50% of the ESRD and 30% of the CKD patients had normal CAs. Troponin T levels significantly correlated with CAs in patients with normal kidney function (r = 0.4, p = 0.005) but not in ESRD and CKD patients (r = 0.2, p = NS, respectively).

Although implantable cardioverter defibrillator (ICD) insertion for primary prevention of sudden cardiac death from lethal ventricular arrhythmias (LVA) is expensive, up to 60% of heart failure patients with ICDs implanted according to current guidelines do not have LVA or device delivered therapy.

Among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.)

Combination therapy may reduce racial/ethnic differences in response to antihypertensives. In this post-hoc analysis, we evaluated treatment response by race/ethnicity among hypertensive adults enrolled in a 12-week, double-blind study in which patients previously uncontrolled (mean sitting systolic blood pressure [MSSBP] ≥150 and 140 mm Hg). Intensive treatment provided greater BP lowering versus moderate treatment throughout the study, regardless of race/ethnicity (474 white, 198 African American, 165 Hispanic individuals). Least-square mean reductions from baseline to week 4 in MSSBP (primary outcome) ranged from 20.4 to 23.5 mm Hg (intensive) versus 17.5 to 19.0 mm Hg (moderate), across racial/ethnic subgroups. Both regimens were well tolerated. Amlodipine/valsartan/HCTZ combination therapy was efficacious across racial/ethnic subgroups. Maximal efficacy was obtained with intensive treatment.

African Americans have a higher prevalence of hypertension and poorer cardiovascular and renal outcomes than white Americans. The objective of this study was to determine whether a telephonic nurse disease management (DM) program designed for African Americans is more effective than a home monitoring program alone to increase blood pressure (BP) control among African Americans enrolled in a national health plan. A prospective randomized controlled study (March 2006-December 2007) was conducted, with 12 months of follow-up on each subject. A total of 5932 health plan members were randomly selected from the population of self-identified African Americans, age 23 and older, in health maintenance organization plans, with hypertension; 954 accepted, 638 completed initial assessment, and 485 completed follow-up assessment. The intervention consisted of telephonic nurse DM (intervention group) including educational materials, lifestyle and diet counseling, and home BP monitor vs. home BP monitor alone (control group). Measurements included proportion with BP < 120/80, mean systolic BP, mean diastolic BP, and frequency of BP self-monitoring. Results revealed that systolic BP was lower in the intervention group (adjusted means 123.6 vs. 126.7 mm Hg, P = 0.03); there was no difference for diastolic BP. The intervention group was 50% more likely to have BP in control (odds ratio [OR] = 1.50, 95% confidence interval [CI] 0.997-2.27, P = 0.052) and 46% more likely to monitor BP at least weekly (OR 1.46, 95% CI 1.07-2.00, P = 0.02) than the control group. A nurse DM program tailored for African Americans was effective at decreasing systolic BP and increasing the frequency of self-monitoring of BP to a greater extent than home monitoring alone. Recruitment and program completion rates could be improved for maximal impact.

Studies using Doppler catheters to assess blood flow velocity and vasodilator reserve in proximal coronary arteries have failed to demonstrate significant improvement immediately after coronary angioplasty. Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic velocity ratio performed distal to a coronary stenosis may provide important information concerning the physiologic significance of coronary artery stenosis. This study was designed to measure these blood flow velocity variables both proximal and distal to a significant coronary artery stenosis in patients undergoing coronary angioplasty.A low profile (0.018-in.) (0.046-cm) Doppler angioplasty guide wire capable of providing spectral flow velocity data was used to measure blood flow velocity, flow reserve and diastolic/systolic velocity ratio both proximal and distal to left anterior descending or left circumflex coronary artery stenosis. These measurements were made in 38 patients undergoing coronary angioplasty and in 12 patients without significant coronary artery disease.Significant improvement in mean time average peak velocity was noted in distal coronary arteries after angioplasty (before 19 +/- 12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s; after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis. Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a significant stenosis was decreased compared with that in normal vessels (1.3 +/- 0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic velocity patterns generally returned to normal, with a significant increase in mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than 0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio measured proximal to a coronary stenosis were not statistically different from values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p greater than 0.10).Flow velocity measurements may be performed distal to a coronary stenosis with the Doppler guide wire. Phasic velocity measurements made proximal to a coronary stenosis differed from those in the distal coronary artery. Both proximal and distal flow reserve measurements made immediately after angioplasty were of limited utility. Changes in distal flow velocity patterns and diastolic/systolic velocity ratio appeared to be more relevant than the hyperemic response in assessing the immediate physiologic outcome of coronary angioplasty.

This post hoc analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) in a diverse population of hypertensive women.INCLUSIVE was a multicenter, prospective, open-label, single-arm trial. Adult subjects had uncontrolled systolic blood pressure (SBP 140-159 mm Hg; 130-159 mm Hg for those with type 2 diabetes mellitus [T2DM]) afteror =4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Mean changes from baseline to treatment end in SBP and diastolic blood pressure (DBP), BP goal attainment, and safety were assessed.Treatment with irbesartan/HCTZ was associated with significant mean reductions in BP (intent-to-treat population, n = 370; SBP/DBP: -22.9/-10.3 +/- 14.7/8.8 mm Hg). Improvements in SBP were observed in all subgroups (p0.001): Caucasian (n = 207) -23.5 +/- 13.5 mm Hg; African American (n = 93) -21.0 +/- 17.2 mm Hg; Hispanics/Latino (n = 66) -23.6 +/- 14.3 mm Hg; age65 years (n = 281) -22.5 +/- 14.7 mm Hg; ageor =65 years (n = 89) -24.3 +/- 14.5 mm Hg; T2DM (n = 97) -19.0 +/- 15.1 mm Hg; and metabolic syndrome (n = 187) -22.1 +/- 14.6 mm Hg. Overall, 82% (95% confidence interval [CI] 78%-86%) of women achieved their SBP goal, 86% (95% CI 83%-90%) achieved their DBP goal, and 76% (95% CI 71%-80%) achieved their dual SBP/DBP goal. Treatments were well tolerated in all groups.Irbesartan/HCTZ treatment was effective and well tolerated in a diverse population of women whose BP was previously uncontrolled on monotherapy.

ACCOMPLISH is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in hypertensive patients at high cardiovascular risk. Enrollment for this trial is now complete and this report describes the clinical characteristics of the study cohort. Patients with hypertension and a previous history of cardiovascular events, strokes or diabetes mellitus were randomized to double-blind treatment with either of the two combination regimens. The data in this report detail the clinical history and demographic characteristics in patients immediately prior to randomization to study drugs. A total of 11,454 patients were randomized. Mean age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46% of patients had a history of acute coronary syndromes, coronary artery bypass grafts or percutaneous coronary interventions; 13% had a history of stroke. A history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only 38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had received previous antihypertensive treatment (74% on at least two drugs); 53% were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive patients at high risk of cardiovascular morbidity and mortality. It is noteworthy that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic criterion of obesity and that 60% of patients are diabetic, possibly reflecting secular trends in clinical disease.

There is growing evidence that nitric oxide (NO)-mediated endothelial dysfunction occurs in hypertension and may represent the earliest stage of target organ damage, which ultimately leads to hypertensive heart disease and heart failure (HF). An understanding of how impaired myocardial microvascular function and flow reserve relate to early remodeling during the transition to HF in patients with hypertension may lead to new therapeutic insights. The hypertrophied heart, which is a feature of the adverse structural remodeling in hypertensive heart disease, may be accompanied by impaired coronary flow reserve (CFR). Reduced CFR could potentially cause subendocardial ischemia during conditions of high metabolic demand, such as uncontrolled hypertension and tachycardia. Such vulnerability of the subendocardium to abnormal perfusion or ischemia may accelerate the progression from compensated hypertrophy to HF. In this review, we discuss preliminary evidence that altered NO balance may contribute to cardiac hypertrophy-mediated myocardial ischemia. We also describe early results with myocardial contrast echocardiography in the postulated transition from compensated hypertrophy to cardiac failure. These data support further evaluation of NO mediators as potential targets for novel therapies in hypertensive heart disease.

99 Background: Breast cancer patients taking tamoxifen (TAM) or an aromatase inhibitor (AI) often develop severe vasomotor symptoms (VMS) yet the only FDA approved non-hormonal treatment for VMS, 7.5 mg paroxetine, has a warning against concomitant use with TAM. Q-122, an orally-available small molecule, is being developed to address this unmet medical need. Results from the Phase 1b study, Q-1001, are presented. Methods: Q-1001 was a Phase 1 open-label, two-dose, dose-escalation study of the safety and preliminary effectiveness of Q-122 in females with breast cancer currently taking TAM or an AI and experiencing an average of at least 7-8 moderate to severe hot flashes per day. Key exclusion criteria included significant renal or hepatic disease, untreated hyperthyroidism and clinically significant abnormal laboratory findings. The study period included a 2 week drug-free screening phase, 28 day treatment phase, and 2 week drug-free follow-up period. Subjects were initially enrolled into Group 1 (100 mg Q-122) followed by Group 2 (200 mg Q-122). Safety was assessed by review of adverse events (AEs), physical findings and laboratory values. The primary efficacy endpoints were mean changes in frequency and severity (hot flash severity score, HFSS) of moderate and severe hot flashes from baseline to Week 4. Menopausal symptoms were assessed using the Greene Climacteric Scale (GCS). Results: 10 and 11 subjects received 100 and 200 mg Q-122 respectively; 8 subjects in each group completed the study. At the end of treatment for groups 1 and 2 respectively, the daily average frequency of hot flashes was reduced from 9.9 to 4.1 and from 8.6 to 3.2, and the mean HFSS was reduced by 62% and 68% from baseline values. Menopausal symptoms assessed using the GCS were significantly reduced from baseline (psychological: -82%; somatic: -65%; vasomotor: -65%). All AEs (n = 29) were either mild (79%) or moderate (21%) in severity and only 3 (all in one subject) were considered possibly related to study drug. Conclusions: Treatment with Q-122 resulted in significant reduction in the frequency and severity of VMS and improvement in menopausal symptoms as assessed by the GCS. No safety issues associated with the use of Q-122 were identified in this study.

OBJECTIVES Previous trials testing isosorbide dinitrate/hydralazine (I/H) were performed in all-male study cohorts, and thus the efficacy of I/H in women was unknown; 40% of the A-HeFT (African-American Heart Failure Trial) cohort were women. We therefore compared outcomes by gender and treatment. BACKGROUND Fixed-dose combined I/H significantly reduced mortality and heart failure hospitalizations and improved quality of life in 1,050 black patients with heart failure treated with background neurohormonal blockade. Previous trials testing I/H were done in all-male study cohorts, and thus the efficacy of I/H in women was unknown. METHODS Baseline characteristics and medications were compared between men and women by I/H and placebo treatment. Survival, time to first heart failure hospitalization, change in quality of life, and event-free survival were compared by gender and treatment. RESULTS At baseline, women had lower hemoglobin and creatinine levels; less renal insufficiency; and higher body mass indexes, diabetes prevalence, and systolic blood pressures; but worse quality of life scores. All-cause mortality was lower in women than in men treated with I/H but without significant treatment interaction by gender. The primary composite score, which weighted mortality, first heart failure hospitalization, and change in quality of life at 6 months, was similarly improved by I/H in men and women. First heart failure hospitalization and event-free survival (time to death or first heart failure hospitalization) were similarly improved in both genders. CONCLUSIONS Fixed-dose I/H improved heart failure outcomes in both men and women in A-HeFT. The I/H significantly improved the primary composite score and event-free survival as well as reduced the risk of first heart failure hospitalizations similarly in both genders. The I/H had a slightly greater mortality benefit in women, but without a significant treatment interaction by gender.

This multicenter, prospective, open-label, single-arm study determined the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients (n=1005), aged 18 years and older, with uncontrolled systolic blood pressure (SBP) of 140-159 mm Hg (130-159 mm Hg for type 2 diabetes mellitus) after at least 4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Enrolled patients (n=844) were aged 57.3+/-11.2 years; 52% were women, 23% were African American, and 14% were Hispanic. Thirty percent had type 2 diabetes mellitus, 46% had metabolic syndrome, and baseline blood pressure was 154.0+/-10.3/91.3+/-8.8 mm Hg. The mean change in SBP from placebo end to the primary end point, Week 18 (intent-to-treat population, n=736) was -21.5+/-14.3 mm Hg (p0.001). The mean change in diastolic blood pressure (DBP) was -10.4+/-8.7 mm Hg (p0.001). The mean Week 18 SBP/DBP was 132.9+/-13.8/81.1+/-9.7 mm Hg. Overall, 77% (95% confidence interval, 74%-80%) of patients achieved SBP goal (140 mm Hg;130 mm Hg for type 2 diabetes mellitus); 83% (95% confidence interval, 80%-86%) achieved DBP goal (90 mm Hg;80 mm Hg for type 2 diabetes mellitus); and 69% (95% confidence interval, 66%-72%) achieved dual SBP/DBP goal. Treatments were well tolerated. This irbesartan/HCTZ treatment regimen achieved SBP goals in more than 75% of patients uncontrolled on monotherapy.

Heart failure (HF) is a progressively debilitating disorder characterized by frequent hospital admissions and high annual mortality rates. Coronary artery disease (CAD), hypertension, and aging are major risk factors for the development/ progression of HF. For years, most of the attention has been focused on HF caused by reduced left ventricular (LV) systolic function, largely attributable to CAD. It is now generally accepted that nearly 50% of elderly patients with HF might have normal or preserved LV systolic function. This condition is commonly referred to as a distinct type of HF caused by LV diastolic dysfunction, and it often accompanies hypertensive heart disease. Isolated diastolic HF is increasingly recognized as the dominant cause of symptoms and hospitalizations from HF in a large proportion of individuals aged 65 and older. However, the clinicians caring for patients with diastolic HF do not fully understand its cause, how it progresses, or how it could be appropriately diagnosed and treated. Because varying degrees of systolic and diastolic dysfunction might coexist in any individual patient, and given the limitation of current diagnostic tools, the overall impact of isolated diastolic HF continues to evolve. Ongoing clinical trials are testing new strategies for treatment of diastolic HF.

Hydralazine and isosorbide dinitrate combination (H+ISDN), angiotensin-converting enzyme inhibitors, and beta-blockers have improved outcomes in heart failure (HF). Analysis of previous trials has shown that H+ISDN appears especially beneficial in African American patients.The African-American Heart Failure Trial (A-HeFT) is double-blind, placebo-controlled, and includes African American patients with stable New York Heart Association Class III-IV HF on standard therapy. Patients must have prior HF-related events and left ventricular ejection fraction (LVEF)or = 35% or LVEF45% with left ventricular internal diastolic dimension2.9 cm/m(2). Randomization to addition of placebo or BiDil (Nitro Med, Inc., Bedford, MA), a fixed combination of H+ISDN, is stratified for beta-blocker usage. All patients are treated and followed until the last patient entered completes 6 months of follow-up. The primary efficacy endpoint is a composite score including quality of life, death, and hospitalization for HF. At least 600 patients will be randomized; the first was randomized in June 2001.In addition to providing additional information on BiDil efficacy in HF, A-HeFT is the first HF trial aimed at a selected subgroup of patients and the first to use a new composite HF score as its primary efficacy endpoint.

The study shows that an integrated, house staff-led process-of-care strategy can significantly improve the treatment rates of high-risk African American patients with dyslipidemia and should improve CVD morbidity and mortality. This model can be readily integrated into an ambulatory clinic; however, future studies should evaluate the cost effectiveness of this strategy by utilizing similar models using more potent or higher-dose statins that are now routinely available.

RAS inhibitors (RASIs/ACE inhibitors & ARBs) have reduced mortality in SHF (EF 45p) in randomized controlled trials. Since, AAs are underrepresented in these trials, whether these results are applicable to AAs with HFPEF is uncertain All cause mortality was

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.