Curr Hypertens Rep (2014) 16:409 DOI 10.1007/s11906-013-0409-5
THERAPEUTIC TRIALS (B PITT, SECTION EDITOR)
Should African Americans with Hypertension Be Treated Differently than Non-African Americans? John M. Flack & Brian A. Ference & Phillip Levy
Published online: 28 December 2013 # Springer Science+Business Media New York 2013
Abstract African Americans have a higher burden of hypertension, more severe blood pressure (BP) elevations, more concurrent risk-enhancing co-morbidities (e.g., diabetes), sub-clinical vascular injury at lower non-hypertensive BP levels, lower BP control rates, and significantly greater risk for adverse pressure-related clinical complications (e.g., stroke, heart failure) than whites. Randomized prospective data from hypertension endpoint trials show a virtually identical percentage reduction in CVD risk for a given magnitude of BP lowering, irrespective of the presence or
This article is part of the Topical Collection on Therapeutic Trials J. M. Flack : B. A. Ference Division of Translational Research and Clinical Epidemiology, Department of Medicine, Wayne State University, Detroit, MI, USA J. M. Flack Division of Endocrinology, Metabolism, and Hypertension, Department of Medicine, Wayne State University, Detroit, MI, USA J. M. Flack Department of Physiology, Wayne State University, Detroit, MI, USA
absence of pre-treatment CVD across a broad range of BP down to pre-treatment BP levels of 110/70 mm Hg. These data, mostly emanating from white populations, do not necessarily inform practitioners as to the level below which BP should be lowered in those with established, long-standing hypertension; however, these data do provide support for initiating hypertension treatment at lower than conventional BP thresholds. A Mendelian randomized study examining the impact of life-long lower SBP levels showed that lifelong exposure to 10 mm Hg lower SBP was associated with an 82 % lesser rate of SBP rise per decade and a 58 % lower CHD risk that was much greater than the 22 % reduction in CHD reported for the same magnitude of SBP reduction in clinical trials. Arguably, it is the hypertension treatment paradigm that merits reexamination. Earlier hypertension treatment in all populations prior to the onset of significant pressure-related target organ injury might conceivably prevent, or at least significantly attenuate, the well documented age-related rise in BP seen in most Western societies. In addition, this treatment paradigm might also reduce the significant residual CVD risk observed under the current recommended approach to hypertension treatment. This new approach to therapy would likely have substantial clinical and public health benefits in the high-risk, under-treated African American population that suffers outsized devastating consequences from inadequate control of BP.
J. M. Flack (*) Department of Medicine, Division of Translational Research and Clinical Epidemiology, Wayne State University, 4201 St. Antoine, Suite 2E-University Health Center, Detroit, MI 48201, USA e-mail: [email protected]
Keywords Hypertension . Blood pressure (BP) target . Diabetes . Chronic kidney disease . CKD . African Americans . Prevention . Treatment . Cardiovascular disease . CVD
B. A. Ference Division of Cardiology, Department of Medicine, Wayne State University, Detroit, MI, USA
Introduction
P. Levy Department of Emergency Medicine, Department of Medicine, Wayne State University, Detroit, MI, USA
Hypertension prevalence, especially the prevalence of extreme BP elevations (>180/110 mm Hg) and earlier onset of hypertension, is significantly more common in African
409, Page 2 of 6
Americans than whites. Sub-clinical manifestations of pressure-related target organ injury are also more common in African Americans than whites, even at BP levels well below conventional hypertension thresholds [1–3]. Blood pressure (BP) control rates are lower amongst African Americans than whites with hypertension even when considering only those taking antihypertensive medication [4]. Fiscella and Holt [5] estimated that eliminating the~8 mm Hg average higher SBP in African Americans compared to whites with hypertension would annually prevent 2,190 excess stroke deaths as well as 5,480 heart disease deaths in African Americans. African Americans have several-fold more pressurerelated adverse clinical events – stroke, congestive heart failure, CKD/ESRD, diabetic retinopathy – than whites [6–9]. These data document the disproportionate occurrence of adverse sub-clinical and clinical pressure-related complications in African Americans that are substantively related to suboptimal levels of BP control in those with established hypertension as well as to the longer duration (dose effect) of BP elevations over their lifespan. There are emerging data supporting the intuitive notion that lifetime CVD risk is related to the longevity of BP elevations[10•].
Rationale for Early Blood Pressure Lowering To Prevent Hypertension Systolic blood pressure (SBP) increases approximately linearly with age in most industrialized societies such that the lifetime risk of developing hypertension approaches 90 % [11, 12]. Multiple epidemiologic studies have demonstrated that increasing SBP is associated with a log-linearly increasing risk of cardiovascular morbidity and mortality beginning well before the development of hypertension [13]. Therefore, if the usual increase in SBP with age could be prevented or slowed, then much of the risk of developing hypertension and its associated cardiovascular morbidity might also be prevented. Importantly, SBP does not appear to increase with age in all societies [14]. As a result, increasing SBP is unlikely to be an inevitable consequence of aging but instead may be preventable. However, the cause of increasing SBP with age is unclear. Several studies have reported that persons with higher baseline SBP appear to experience a faster rate of rise in SBP over time as compared to persons with lower levels of SBP [11, 15]. This observation has led to the hypothesis that increased SBP causes vascular injury or dysfunction, which in turn leads to higher SBP and a cycle of accumulating vascular injury that manifests as increasing SBP with age [16]. The direct implication of this hypothesis, if proven, would be that lowering SBP beginning before the development of hypertension may interrupt this cycle of cumulative vascular injury,
Curr Hypertens Rep (2014) 16:409
thereby preventing or slowing the usual age-related rise in SBP and thus reduce the risk of subsequent pressureassociated morbidity much more effectively than the current paradigm of waiting to initiate BP lowering therapy until hypertension has already developed. Two randomized trials have tested the hypothesis that lowering SBP before the development of hypertension may slow the usual age-related rise in SBP and thereby prevent or delay the development of hypertension [17–19]. In the Trial of Preventing Hypertension (TROPHY) study, two years of treatment with candesartan reduced the incidence of hypertension by 66 % (p
THERAPEUTIC TRIALS (B PITT, SECTION EDITOR)
Should African Americans with Hypertension Be Treated Differently than Non-African Americans? John M. Flack & Brian A. Ference & Phillip Levy
Published online: 28 December 2013 # Springer Science+Business Media New York 2013
Abstract African Americans have a higher burden of hypertension, more severe blood pressure (BP) elevations, more concurrent risk-enhancing co-morbidities (e.g., diabetes), sub-clinical vascular injury at lower non-hypertensive BP levels, lower BP control rates, and significantly greater risk for adverse pressure-related clinical complications (e.g., stroke, heart failure) than whites. Randomized prospective data from hypertension endpoint trials show a virtually identical percentage reduction in CVD risk for a given magnitude of BP lowering, irrespective of the presence or
This article is part of the Topical Collection on Therapeutic Trials J. M. Flack : B. A. Ference Division of Translational Research and Clinical Epidemiology, Department of Medicine, Wayne State University, Detroit, MI, USA J. M. Flack Division of Endocrinology, Metabolism, and Hypertension, Department of Medicine, Wayne State University, Detroit, MI, USA J. M. Flack Department of Physiology, Wayne State University, Detroit, MI, USA
absence of pre-treatment CVD across a broad range of BP down to pre-treatment BP levels of 110/70 mm Hg. These data, mostly emanating from white populations, do not necessarily inform practitioners as to the level below which BP should be lowered in those with established, long-standing hypertension; however, these data do provide support for initiating hypertension treatment at lower than conventional BP thresholds. A Mendelian randomized study examining the impact of life-long lower SBP levels showed that lifelong exposure to 10 mm Hg lower SBP was associated with an 82 % lesser rate of SBP rise per decade and a 58 % lower CHD risk that was much greater than the 22 % reduction in CHD reported for the same magnitude of SBP reduction in clinical trials. Arguably, it is the hypertension treatment paradigm that merits reexamination. Earlier hypertension treatment in all populations prior to the onset of significant pressure-related target organ injury might conceivably prevent, or at least significantly attenuate, the well documented age-related rise in BP seen in most Western societies. In addition, this treatment paradigm might also reduce the significant residual CVD risk observed under the current recommended approach to hypertension treatment. This new approach to therapy would likely have substantial clinical and public health benefits in the high-risk, under-treated African American population that suffers outsized devastating consequences from inadequate control of BP.
J. M. Flack (*) Department of Medicine, Division of Translational Research and Clinical Epidemiology, Wayne State University, 4201 St. Antoine, Suite 2E-University Health Center, Detroit, MI 48201, USA e-mail: [email protected]
Keywords Hypertension . Blood pressure (BP) target . Diabetes . Chronic kidney disease . CKD . African Americans . Prevention . Treatment . Cardiovascular disease . CVD
B. A. Ference Division of Cardiology, Department of Medicine, Wayne State University, Detroit, MI, USA
Introduction
P. Levy Department of Emergency Medicine, Department of Medicine, Wayne State University, Detroit, MI, USA
Hypertension prevalence, especially the prevalence of extreme BP elevations (>180/110 mm Hg) and earlier onset of hypertension, is significantly more common in African
409, Page 2 of 6
Americans than whites. Sub-clinical manifestations of pressure-related target organ injury are also more common in African Americans than whites, even at BP levels well below conventional hypertension thresholds [1–3]. Blood pressure (BP) control rates are lower amongst African Americans than whites with hypertension even when considering only those taking antihypertensive medication [4]. Fiscella and Holt [5] estimated that eliminating the~8 mm Hg average higher SBP in African Americans compared to whites with hypertension would annually prevent 2,190 excess stroke deaths as well as 5,480 heart disease deaths in African Americans. African Americans have several-fold more pressurerelated adverse clinical events – stroke, congestive heart failure, CKD/ESRD, diabetic retinopathy – than whites [6–9]. These data document the disproportionate occurrence of adverse sub-clinical and clinical pressure-related complications in African Americans that are substantively related to suboptimal levels of BP control in those with established hypertension as well as to the longer duration (dose effect) of BP elevations over their lifespan. There are emerging data supporting the intuitive notion that lifetime CVD risk is related to the longevity of BP elevations[10•].
Rationale for Early Blood Pressure Lowering To Prevent Hypertension Systolic blood pressure (SBP) increases approximately linearly with age in most industrialized societies such that the lifetime risk of developing hypertension approaches 90 % [11, 12]. Multiple epidemiologic studies have demonstrated that increasing SBP is associated with a log-linearly increasing risk of cardiovascular morbidity and mortality beginning well before the development of hypertension [13]. Therefore, if the usual increase in SBP with age could be prevented or slowed, then much of the risk of developing hypertension and its associated cardiovascular morbidity might also be prevented. Importantly, SBP does not appear to increase with age in all societies [14]. As a result, increasing SBP is unlikely to be an inevitable consequence of aging but instead may be preventable. However, the cause of increasing SBP with age is unclear. Several studies have reported that persons with higher baseline SBP appear to experience a faster rate of rise in SBP over time as compared to persons with lower levels of SBP [11, 15]. This observation has led to the hypothesis that increased SBP causes vascular injury or dysfunction, which in turn leads to higher SBP and a cycle of accumulating vascular injury that manifests as increasing SBP with age [16]. The direct implication of this hypothesis, if proven, would be that lowering SBP beginning before the development of hypertension may interrupt this cycle of cumulative vascular injury,
Curr Hypertens Rep (2014) 16:409
thereby preventing or slowing the usual age-related rise in SBP and thus reduce the risk of subsequent pressureassociated morbidity much more effectively than the current paradigm of waiting to initiate BP lowering therapy until hypertension has already developed. Two randomized trials have tested the hypothesis that lowering SBP before the development of hypertension may slow the usual age-related rise in SBP and thereby prevent or delay the development of hypertension [17–19]. In the Trial of Preventing Hypertension (TROPHY) study, two years of treatment with candesartan reduced the incidence of hypertension by 66 % (p
