... MD, FACC; Eduardo Ortiz, MD, MPH; Efrain Reisin, MD, FASN**; Michael W. Rich, MD, FACC; Do... more ... MD, FACC; Eduardo Ortiz, MD, MPH; Efrain Reisin, MD, FASN**; Michael W. Rich, MD, FACC; Douglas D. Schocken, MD, FACC, FAHA; Michael A. Weber, MD, FACC§§; Deborah J. Wesley, RN, BSN ACCF TASK FORCE MEMBERS Robert A. Harrington, MD, FACC ...
The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepri... more The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) <140 mmHg and achieved SBP level by the end of 12 months in both treatment groups. Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p < 0.001) predictors in multivariate analyses. Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control <140 mmHg were region (USA…
There are many parallels between renal glomerular and vascular structure and function. Endothelia... more There are many parallels between renal glomerular and vascular structure and function. Endothelial cells line both glomeruli and vessels, and mesangial cells are modified vascular smooth muscle cells (VSMC) (1-3). Endothelial and mesangial cells together account for about 85% of the total number of cells that make up the glomerulus (1 2), and these cells are distinguished by their biological
Journal of the American Society of Hypertension : JASH, 2015
Ambulatory blood pressure parameters, nocturnal dipping and morning surge, are associated with ca... more Ambulatory blood pressure parameters, nocturnal dipping and morning surge, are associated with cardiovascular outcomes in several populations. While significant variation exists between racial groups in ambulatory blood pressure measurements and the incidence of cardiovascular disease, the effect of race on the associations of dipping and morning surge with cardiovascular outcomes is unknown. In a prospective analysis of 197 African American and 197 Japanese individuals with non-diabetic chronic kidney disease matched by age and renal function, we analyzed the associations of dipping and morning surge with cardiovascular events for both races and assessed whether these relations differed by race. Higher sleep-trough morning surge was independently associated with cardiovascular events in Japanese (hazard ratio, 1.93 per 10 mm Hg; 95% confidence interval, 1.20-3.10) but not in African American participants, with race an effect modifier (P-value <.01). Dipping was not associated wi...
Diabetes increases cardiovascular (CV) risk to a similar extent as myocardial infarction. Epidemi... more Diabetes increases cardiovascular (CV) risk to a similar extent as myocardial infarction. Epidemiologic data support the same concept for the presence of Stage 3 (ie, glomerular filtration rate of < 60 mL/min) or higher nephropathy without diabetes. The most common cause of end-stage kidney disease requiring dialysis is diabetes. Hence, CV risk is highest among those with kidney disease and diabetes. Glycemic control in the context of CV risk reduction among patients with kidney disease has not been the focus of any specific trial; however, secondary analyses of trials, primarily in type 1 diabetes, have looked at this issue. Nevertheless, the outcome data are sparse. What can be said, however, is that failure to achieve reasonable glycemic control (ie, glycated hemoglobin < 7.5%) is associated with a higher risk of CV events and hospitalizations for CV events and infections among those with advanced kidney disease. The impact of poor glycemic control on kidney disease progres...
Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascul... more Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascular events and cardiovascular mortality. During 2014, several research efforts focused on clarifying the complex pathophysiology, assessing the prognostic associations and improving the treatment of cardiovascular disease in patients with CKD.
This article begins with a brief overview of the therapeutic agents used in the treatment of hear... more This article begins with a brief overview of the therapeutic agents used in the treatment of heart failure, with a special emphasis on pharmacologic agents that block the renin-angiotensin system (RAS). The discussion then builds upon the basic pathophysiology concepts introduced earlier in this issue to explain how therapies commonly used in heart failure affect kidney function. Against this background, a few of the common clinical dilemmas that clinicians often encounter when treating patients with agents that block the RAS system are discussed.
Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men ... more Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men and women, current evidence suggests that it has a much stronger effect on the risk of coronary heart disease (CHD) in women than in men. Moreover, diabetic women have not experienced the decline in CHD mortality observed in diabetic men and individuals without diabetes over the past three decades. Apart from a more pronounced direct effect of diabetes on the vascular wall, this greater impact of diabetes on CHD risk in women could be associated with a heavier burden of other traditional cardiovascular risk factors within the context of the metabolic syndrome, a stronger effect of the metabolic syndrome on CVD, and a less aggressive management of the various risk factors in diabetic women compared with men. This article discusses the recent evidence on the gender differences in the outcomes of CVD and the management of risk factors associated with diabetes and the metabolic syndrome, highlighting the need for better treatment strategies of diabetes and the other components of the metabolic syndrome in diabetic women.
The presence of proteinuria is a well-known risk factor for both the progression of renal disease... more The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients. Am J Kidney Dis 49:12-26.
OBJECTIVE -We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapam... more OBJECTIVE -We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT).
Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events i... more Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoi...
Background: -Blockers have been shown to be ben- eficial in the treatment and prevention of heart... more Background: -Blockers have been shown to be ben- eficial in the treatment and prevention of heart failure (HF) in the general population, but they have not been assessed for their association with nonfatal HF in a na- tionally representative population of long-term dialysis patients. Methods: We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data
International Journal of Heat and Fluid Flow, 2010
March 17, 2010 http://content.onlinejacc.org located on the World Wide Web at: The online version... more March 17, 2010 http://content.onlinejacc.org located on the World Wide Web at: The online version of this article, along with updated information and services, is by on March 17, 2010 content.onlinejacc.org Downloaded from VDA Net srl
The aim of this work was to review evidence on the contribution of the metabolic syndrome to diab... more The aim of this work was to review evidence on the contribution of the metabolic syndrome to diabetes and atherosclerosis, to evaluate the effects of the thiazolidinediones (TZDs) on cardiovascular risk, and to assess the clinical use of TZDs and their associated risks and benefits. Participants were a multidisciplinary panel of experts in endocrinology, cardiology, and nephrology. Available studies on hyperglycemia, hyperinsulinemia, beta-cell function, dyslipidemia, obesity, hypertension, inflammation, endothelial dysfunction, and vascular reactivity were reviewed through presentations by the experts. Assessments were made regarding the associations between characteristics of the metabolic syndrome, type 2 diabetes, and cardiovascular disease, along with the place of TZDs in therapy and management of related adverse clinical events. A panel was convened in November 2002 to develop conclusions based on scientific evidence presented during the meeting. Summary statements were evaluated based on strength and clinical relevance of the data and approved by all panel members. Many characteristics of the metabolic syndrome are present before diabetes develops that greatly contribute to the cardiovascular disease burden associated with the progression of diabetes, such as atherosclerosis and coronary artery disease. Insulin resistance is a fundamental component of the metabolic syndrome, and interventions to improve insulin sensitivity are associated with positive cardiovascular effects. From current experimental and clinical data, TZDs appear to reduce risk factors for future cardiovascular events in patients with type 2 diabetes. Study data up to 2 years have demonstrated that TZDs effectively maintain glycemic control in patients with type 2 diabetes, which is attributed to their insulin-sensitizing effects and preservation of beta-cell function. Potential adverse events of TZDs include weight gain and edema, which are generally manageable. Aside from improving insulin sensitivity, TZDs improve lipid profiles, favorably alter deposition of adipose tissue to the periphery rather than visceral areas, decrease markers of inflammation and endothelial dysfunction, and restore vascular reactivity. These pleiotropic effects have the potential to improve cardiovascular outcomes in patients with type 2 diabetes. Trials are underway to confirm this potentially beneficial addition to proven therapies for hypertension, dyslipidemia, and atherosclerosis.
Journal of the American Society of Hypertension, 2014
The epidemiology, evaluation, and management of severe and resistant hypertension in the United S... more The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of ≥160 mm Hg (or ≥ 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2). The first sham-controlled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice. At present, the focus on the management of severe and resistant hypertension will be through careful evaluation for pseudo-resistance and secondary forms of hypertension, appropriate use of combination pharmacologic therapy, and greater utility of specialists in hypertension.
bers are most likely to depend on medication and have high adherence rates. Yet they also have hi... more bers are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply
... MD, FACC; Eduardo Ortiz, MD, MPH; Efrain Reisin, MD, FASN**; Michael W. Rich, MD, FACC; Do... more ... MD, FACC; Eduardo Ortiz, MD, MPH; Efrain Reisin, MD, FASN**; Michael W. Rich, MD, FACC; Douglas D. Schocken, MD, FACC, FAHA; Michael A. Weber, MD, FACC§§; Deborah J. Wesley, RN, BSN ACCF TASK FORCE MEMBERS Robert A. Harrington, MD, FACC ...
The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepri... more The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;140 mmHg and achieved SBP level by the end of 12 months in both treatment groups. Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) predictors in multivariate analyses. Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;140 mmHg were region (USA…
There are many parallels between renal glomerular and vascular structure and function. Endothelia... more There are many parallels between renal glomerular and vascular structure and function. Endothelial cells line both glomeruli and vessels, and mesangial cells are modified vascular smooth muscle cells (VSMC) (1-3). Endothelial and mesangial cells together account for about 85% of the total number of cells that make up the glomerulus (1 2), and these cells are distinguished by their biological
Journal of the American Society of Hypertension : JASH, 2015
Ambulatory blood pressure parameters, nocturnal dipping and morning surge, are associated with ca... more Ambulatory blood pressure parameters, nocturnal dipping and morning surge, are associated with cardiovascular outcomes in several populations. While significant variation exists between racial groups in ambulatory blood pressure measurements and the incidence of cardiovascular disease, the effect of race on the associations of dipping and morning surge with cardiovascular outcomes is unknown. In a prospective analysis of 197 African American and 197 Japanese individuals with non-diabetic chronic kidney disease matched by age and renal function, we analyzed the associations of dipping and morning surge with cardiovascular events for both races and assessed whether these relations differed by race. Higher sleep-trough morning surge was independently associated with cardiovascular events in Japanese (hazard ratio, 1.93 per 10 mm Hg; 95% confidence interval, 1.20-3.10) but not in African American participants, with race an effect modifier (P-value <.01). Dipping was not associated wi...
Diabetes increases cardiovascular (CV) risk to a similar extent as myocardial infarction. Epidemi... more Diabetes increases cardiovascular (CV) risk to a similar extent as myocardial infarction. Epidemiologic data support the same concept for the presence of Stage 3 (ie, glomerular filtration rate of < 60 mL/min) or higher nephropathy without diabetes. The most common cause of end-stage kidney disease requiring dialysis is diabetes. Hence, CV risk is highest among those with kidney disease and diabetes. Glycemic control in the context of CV risk reduction among patients with kidney disease has not been the focus of any specific trial; however, secondary analyses of trials, primarily in type 1 diabetes, have looked at this issue. Nevertheless, the outcome data are sparse. What can be said, however, is that failure to achieve reasonable glycemic control (ie, glycated hemoglobin < 7.5%) is associated with a higher risk of CV events and hospitalizations for CV events and infections among those with advanced kidney disease. The impact of poor glycemic control on kidney disease progres...
Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascul... more Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascular events and cardiovascular mortality. During 2014, several research efforts focused on clarifying the complex pathophysiology, assessing the prognostic associations and improving the treatment of cardiovascular disease in patients with CKD.
This article begins with a brief overview of the therapeutic agents used in the treatment of hear... more This article begins with a brief overview of the therapeutic agents used in the treatment of heart failure, with a special emphasis on pharmacologic agents that block the renin-angiotensin system (RAS). The discussion then builds upon the basic pathophysiology concepts introduced earlier in this issue to explain how therapies commonly used in heart failure affect kidney function. Against this background, a few of the common clinical dilemmas that clinicians often encounter when treating patients with agents that block the RAS system are discussed.
Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men ... more Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men and women, current evidence suggests that it has a much stronger effect on the risk of coronary heart disease (CHD) in women than in men. Moreover, diabetic women have not experienced the decline in CHD mortality observed in diabetic men and individuals without diabetes over the past three decades. Apart from a more pronounced direct effect of diabetes on the vascular wall, this greater impact of diabetes on CHD risk in women could be associated with a heavier burden of other traditional cardiovascular risk factors within the context of the metabolic syndrome, a stronger effect of the metabolic syndrome on CVD, and a less aggressive management of the various risk factors in diabetic women compared with men. This article discusses the recent evidence on the gender differences in the outcomes of CVD and the management of risk factors associated with diabetes and the metabolic syndrome, highlighting the need for better treatment strategies of diabetes and the other components of the metabolic syndrome in diabetic women.
The presence of proteinuria is a well-known risk factor for both the progression of renal disease... more The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients. Am J Kidney Dis 49:12-26.
OBJECTIVE -We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapam... more OBJECTIVE -We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT).
Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events i... more Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoi...
Background: -Blockers have been shown to be ben- eficial in the treatment and prevention of heart... more Background: -Blockers have been shown to be ben- eficial in the treatment and prevention of heart failure (HF) in the general population, but they have not been assessed for their association with nonfatal HF in a na- tionally representative population of long-term dialysis patients. Methods: We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data
International Journal of Heat and Fluid Flow, 2010
March 17, 2010 http://content.onlinejacc.org located on the World Wide Web at: The online version... more March 17, 2010 http://content.onlinejacc.org located on the World Wide Web at: The online version of this article, along with updated information and services, is by on March 17, 2010 content.onlinejacc.org Downloaded from VDA Net srl
The aim of this work was to review evidence on the contribution of the metabolic syndrome to diab... more The aim of this work was to review evidence on the contribution of the metabolic syndrome to diabetes and atherosclerosis, to evaluate the effects of the thiazolidinediones (TZDs) on cardiovascular risk, and to assess the clinical use of TZDs and their associated risks and benefits. Participants were a multidisciplinary panel of experts in endocrinology, cardiology, and nephrology. Available studies on hyperglycemia, hyperinsulinemia, beta-cell function, dyslipidemia, obesity, hypertension, inflammation, endothelial dysfunction, and vascular reactivity were reviewed through presentations by the experts. Assessments were made regarding the associations between characteristics of the metabolic syndrome, type 2 diabetes, and cardiovascular disease, along with the place of TZDs in therapy and management of related adverse clinical events. A panel was convened in November 2002 to develop conclusions based on scientific evidence presented during the meeting. Summary statements were evaluated based on strength and clinical relevance of the data and approved by all panel members. Many characteristics of the metabolic syndrome are present before diabetes develops that greatly contribute to the cardiovascular disease burden associated with the progression of diabetes, such as atherosclerosis and coronary artery disease. Insulin resistance is a fundamental component of the metabolic syndrome, and interventions to improve insulin sensitivity are associated with positive cardiovascular effects. From current experimental and clinical data, TZDs appear to reduce risk factors for future cardiovascular events in patients with type 2 diabetes. Study data up to 2 years have demonstrated that TZDs effectively maintain glycemic control in patients with type 2 diabetes, which is attributed to their insulin-sensitizing effects and preservation of beta-cell function. Potential adverse events of TZDs include weight gain and edema, which are generally manageable. Aside from improving insulin sensitivity, TZDs improve lipid profiles, favorably alter deposition of adipose tissue to the periphery rather than visceral areas, decrease markers of inflammation and endothelial dysfunction, and restore vascular reactivity. These pleiotropic effects have the potential to improve cardiovascular outcomes in patients with type 2 diabetes. Trials are underway to confirm this potentially beneficial addition to proven therapies for hypertension, dyslipidemia, and atherosclerosis.
Journal of the American Society of Hypertension, 2014
The epidemiology, evaluation, and management of severe and resistant hypertension in the United S... more The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of ≥160 mm Hg (or ≥ 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2). The first sham-controlled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice. At present, the focus on the management of severe and resistant hypertension will be through careful evaluation for pseudo-resistance and secondary forms of hypertension, appropriate use of combination pharmacologic therapy, and greater utility of specialists in hypertension.
bers are most likely to depend on medication and have high adherence rates. Yet they also have hi... more bers are most likely to depend on medication and have high adherence rates. Yet they also have high rates of smoking (29%) and alcohol use (average, 104 times per year) and are less likely to exercise regularly. Group C members are most likely to forget to take medication, are likely to be obese, and find it most difficult to comply
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Papers by George Bakris