Keith C. Ferdinand

Resistant Hypertension: Diagnosis, Evaluation, and Treatment A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research

Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

Resistant Hypertension: Diagnosis, Evaluation, and Treatment. A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research

Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents

This document has been developed as an expert consensus document by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA), in collaboration with the American Academy of Neurology (AAN), the American College of Physicians (ACP), the American Geriatrics Society (AGS), the American Society of Hypertension (ASH), the American Society of Nephrology (ASN), the American Society for Preventive Cardiology (ASPC), the Association of Black Cardiologists (ABC), and the European Society of Hypertension (ESH). Expert consensus documents are intended to inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by expert consensus documents are so designed because the evidence base, the experience with technology, and/or clinical practice are not considered sufficiently well developed to be evaluated by the formal ACCF/AHA practice guidelines process. Often the topic is the subject of considerable ongoing investigation. Thus, the reader should view the expert consensus document as the best attempt of the ACCF and document cosponsors to inform and guide clinical practice in areas where rigorous evidence may not yet be available or evidence to date is not widely applied to clinical practice. When feasible, expert consensus documents include indications or contraindications. Typically, formal recommendations are not provided in expert consensus documents as these documents do not formally grade the quality of evidence, and the provision of “Recommendations” is felt to be more appropriately within the purview of the ACCF/AHA practice guidelines. However, recommendations from ACCF/AHA practice guidelines and ACCF appropriate use criteria are presented where pertinent to the discussion. The writing committee is in agreement with these recommendations. Finally, some topics covered by expert consensus documents will be addressed subsequently by the ACCF/AHA …

Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008

Background— Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure control. Methods and Results— Subjects included 13 375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANESs) subdivided into 1988 to 1994, 1999 to 2004, and 2005 to 2008. Uncontrolled hypertension was defined as blood pressure ≥140/≥90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking ≥3 antihypertensive medications. Framingham 10-year coronary risk was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1 to 2 blood pressure medications, and aTRH across all 3 survey periods. More than half of uncontrolled hypertensives were untreated across surveys, including 52.2% in 2005 to 2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthcare visits (0 to 1 per year), body mass index <25 kg/m2, absence of chronic kidney disease, and Framingham 10-year coronary risk <10% (P<0.01). Most treated uncontrolled patients reported taking 1 to 2 blood pressure medications, a proxy for therapeutic inertia. This group was older, had higher Framingham 10-year coronary risk than patients controlled on 1 to 2 medications (P<0.01), and comprised 34.4% of all uncontrolled and 72.0% of treated uncontrolled patients in 2005 to 2008. We found that aTRH increased from 15.9% (1998–2004) to 28.0% (2005–2008) of treated patients (P<0.001). Clinical characteristics associated with aTRH included ≥4 visits per year, obesity, chronic kidney disease, and Framingham 10-year coronary risk >20% (P<0.01). Conclusion— Untreated, undertreated, and aTRH patients have consistent characteristics that could inform strategies to improve blood pressure control by decreasing untreated hypertension, reducing therapeutic inertia in undertreated patients, and enhancing therapeutic efficiency in aTRH.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2

An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.

Coronary Heart Disease in African Americans

African Americans have the highest overall mortality rate from coronary heart disease (CHD) of any ethnic group in the United States, particularly out-of-hospital deaths, and especially at younger ages. Although all of the reasons for the excess CHD mortality among African Americans have not been elucidated, it is clear that there is a high prevalence of certain coronary risk factors, delay in the recognition and treatment of high-risk individuals, and limited access to cardiovascular care. The clinical spectrum of acute and chronic CHD in African Americans is similar to that in whites. However, African Americans have a higher risk of sudden cardiac death and present more often with unstable angina and non-Q-wave myocardial infarction than whites. African Americans have less obstructive coronary artery disease on angiography, but may have a similar or greater total burden of coronary atherosclerosis. Ethnic differences in the clinical manifestations of CHD may be explained largely by the inherent heterogeneity of the coronary syndromes, and the disproportionately high prevalence and severity of hypertension and type 2 diabetes in African Americans. Identification of high-risk individuals for vigorous risk factor modification-especially control of hypertension, regression of left ventricular hypertrophy, control of diabetes, treatment of dyslipidemia, and smoking cessation--is key for successful risk reduction.

Early and Sustained Benefit on Event-Free Survival and Heart Failure Hospitalization From Fixed-Dose Combination of Isosorbide Dinitrate/Hydralazine Consistency Across Subgroups in the African-American Heart Failure Trial

Background— We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. Methods and Results— Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). Conclusions— FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

Epidemiology of Hypertension and Cardiovascular Disease in African Americans

Hypertension is a major cause of cardiovascularrenal morbidity and mortality and all‐cause mortality. It is a highly significant problem for African Americans; about 30% of all deaths in this population are attributable to hypertension. Compared with whites, hypertension in African Americans is more prevalent, occurs earlier in life, is more severe, and is more often associated with target organ injury such as left ventricular hypertrophy and other cardiovascular complications. Only 25% of all African Americans with hypertension and fewer than 50% of those receiving drug treatment attain a blood pressure <140/90 mm Hg. These control rates are some‐what less than in white Americans. Enhanced awareness and understanding of the epidemiologic patterns of hypertension, other cardiovascular risk factors, risk‐factor control rates, and factors influencing these control rates should lead to better approaches to riskfactor control. This most likely would result in a reduction of cardiovascular disease complications.

Emergence of Nonobstructive Coronary Artery Disease: A Woman's Problem and Need for Change in Definition on Angiography.

Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges.

Heart rate variability for risk stratification of life-threatening arrhythmias

[The following is a position statement prepared by the Cardiovascular Technology Assessment Committee: LEONARD S. DREIFUS, MD, FACC, Chairman, JAI B. AGARWAL, MBBS, FACC, ELIAS H. BOTVINICK, MD, FACC, KEITH C. FERDINAND, MD, FACC, CHARLES FISCH, MD, FACC, ex officio, JOHN D. FISHER, MD, FACC, J. WARD KENNEDY, MD, FACC, ex officio, RICHARD E. KERBER, MD, FACC, CHARLES R. LAMBERT, MD, FACC, OKIKE N. OKIKE, MD, FACC, ERIC N. PRYSTOWSKY, MD, FACC, SANJEEV V. SAKSENA, MBBS, FACC, JOHN S. SCHROEDER, MD, FACC, ex officio, DAVID O. WILLIAMS, MD, FACC. This position statement was approved by the Board of Trustees of the American College of Cardiology on March 13, 1993. Reprints are available from: Educational Products Sales and Marketing; 9111 Old Georgetown Road; Bethesda, MD 20814; 800/257-4740.]