Appropriate Blood Pressure Control In Diabetes Research Articles

Effects of medical therapies on retinopathy progression in type 2 diabetes: Is blood pressure control the lower the better?

Effects of medical therapies on retinopathy progression in type 2 diabetes: Is blood pressure control the lower the better?

Lower Blood Pressure Goals for Cardiovascular and Renal Risk Reduction: Are They Defensible?

Most guidelines in the Western world uniformly recommend two blood pressure (BP) goals, <140 ⁄90 mm Hg for the general population and <130 ⁄80 mm Hg for those with diabetes or chronic kidney disease (CKD). These recommendations for a lower BP goal in these specific groups stem from retrospective data analyses that suggest a slower decline in CKD and greater cardiovascular disease (CVD) risk reduction when BP is <130 ⁄80 mm Hg. The question to be addressed: are these more aggressive BP goals defensible based on appropriately powered prospective outcome trials? Meta-analyses of all clinical trials, to date, demonstrate that reducing BP reduces risk for stroke and coronary heart disease. However, none have achieved a mean BP goal of <130 ⁄80 mm Hg. This lack of lower BP goal achievement is even true in CVD outcome trials of diabetes. In trials such as the United Kingdom Prospective Diabetes Study (UKPDS) and the Hypertension Optimal Treatment Trial (HOT), the systolic BP was more than 10 mm Hg higher than this lower goal. Nevertheless, a benefit occurred on CVD reduction. One prospective study that achieved this lower BP goal in patients with diabetes and no overt nephropathy was the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. This trial demonstrated reduced CV risk, but there was no difference between the groups with a mean systolic pressure of 138 mm Hg vs the intensive group at 132 mm Hg. A summary of large CVD outcome trials during the past decade with the relative CVD risk reduction and achieved mean systolic BP are presented in the Figure. It is clear that none of the trials achieved a systolic BP below 130 mm Hg. The definitive answer regarding whether lower levels of systolic BP further reduce CVD risk will come from the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial within the year. If negative, the BP goal of <130 ⁄80 mm Hg will be clearly indefensible.

Abstract 3781: A Reduction in Urinary Albumin Excretion is Associated with a Decrease in 10-year Cardiovascular Mortality in Hypertensive Type 2 Diabetic Patients

Urinary albumin excretion (UAE) is one of the strongest predictors of both adverse renal and cardiovascular outcomes in patients with type 2 diabetes. Although measurement of UAE is widely recommended, there is little available data to suggest that reducing UAE translates into a reduction in cardiovascular mortality. We assessed whether an early reduction in UAE is associated with improved long-term cardiovascular mortality in hypertensive type 2 diabetic patients with normo, micro, or overt albuminuria at baseline. The study is a 10-year longitudinal analysis of a prospective, randomized study- the Appropriate Blood Pressure Control in Diabetes (ABCD) trial including 393 type 2 diabetic patients with hypertension. We evaluated the association between the change in UAE from baseline to 1-year with the incidence of all cause and cardiovascular mortality over a ten year period. Our results revealed that a reduction in log UAE achieved at one-year was one of the strongest predictors of reduced cardiovascular mortality in a multivariable model that adjusted for multiple cardiovascular risk factors (HR1.42, 95% CI 1.06 – 1.92). This association was at all levels of UAE, normo, micro and overt albuminuria. In conclusion, an early reduction in UAE even at the normoalbuminuria level is associated with improvements in long-term cardiovascular mortality. Our data support current guideline recommendations to screen for UAE in all type 2 diabetic patients, but also suggest that serial UAE measurements after initiation of therapy may have clinical value. Prospective studies addressing this approach to care are needed prior to widespread adoption in practice.

Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial

The hypertensive and normotensive Appropriate Blood Pressure Control in Diabetes (ABCD) studies were prospective, randomized, interventional clinical trials with 5 years of follow-up that examined the role of intensive versus standard blood pressure control in a total of 950 patients with type 2 diabetes mellitus. In the hypertensive ABCD study, a significant decrease in mortality was detected in the intensive blood pressure control group when compared with the standard blood pressure control group. There was also a marked reduction in the incidence of myocardial infarction when patients were randomly assigned to initial antihypertensive therapy with angiotensin-converting-enzyme inhibition rather than calcium channel blockade. The results of the normotensive ABCD study included associations between intensive blood pressure control and significant slowing of the progression of nephropathy (as assessed by urinary albumin excretion) and retinopathy, and fewer strokes. In both the hypertensive and normotensive studies, mean renal function (as assessed by 24 h creatinine clearance) remained stable during 5 years of either intensive or standard blood pressure intervention in patients with normoalbuminuria (<30 mg/24 h) or microalbuminuria (30-300 mg/24 h) at baseline. By contrast, the rate of creatinine clearance in patients with overt diabetic nephropathy (>300 mg/24 h; albuminuria) at baseline decreased by an average of 5 ml/min/year in spite of either intensive or standard blood pressure control. Analysis of the results of 5 years of follow-up revealed a highly significant correlation of all-cause and cardiovascular mortality with left ventricular mass and severity of albuminuria.

Diabetic autonomic neuropathy is associated with an increased incidence of strokes

Objective: To ascertain risk factors associated with the occurrence of strokes in type 2 diabetes over a 5-year follow-up period. Background: Diabetic patients are at increased risk for cardiovascular disease when compared to non-diabetic patients. Strokes are a significant source of morbidity and mortality. Design/Methods: We evaluated the relationship between a number cardiovascular risk factors in 950 normotensive and hypertensive type 2 diabetic patients enrolled in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial on the incidence of stroke. We analyzed data from this longitudinal study to evaluate the relationships between various baseline risk factors and the occurrence of strokes. Results: A number of baseline risk factors were associated with the occurrence of strokes including history of a stroke ( p=0.02) and heart failure ( p=0.004) at baseline, age ( p=0.004), longer duration of diabetes ( p=0.03), higher systolic blood pressure ( p=0.005), an abnormal ankle/brachial index ( p=0.05), decreased duration on the exercise treadmill test at baseline ( p=0.009), the presence of retinopathy ( p=0.02), overt albuminuria ( p=0.03) and the presence of diabetic autonomic neuropathy (DAN) as defined as a borderline or abnormal E/I ratio ( p=0.016). Other variables that were tested but were not significantly associated included gender, duration of hypertension, diastolic blood pressure and smoking. When applying a multiple logistic regression model, DAN (OR=2.2, 95% CI=1.10–4.44), along with a history of heart failure (OR=7.4, 95% CI=2.12–26.15) and strokes (OR=3.4, 95% CI=1.02–11.00) at baseline were each associated with the occurrence of strokes. Conclusions: In the present study of type 2 diabetic patients, DAN is a significant independent risk factor for the occurrence of stroke. This may occur due to accelerated cerebral vascular damage and alterations in the regulation of cerebral blood flow in diabetic patients with DAN.

Differential effects of antihypertensive agents on electrocardiographic voltage: results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial

Background Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events. Methods We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis. Results In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P = .002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events. Conclusions In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all, of the effect of enalapril in this study.

Evaluation and Treatment of Patients With Systemic Hypertension

A 65-year-old man presented for evaluation of high blood pressure found on screening at a local health fair. History and physical examination did not show any signs or symptoms suggestive of a secondary cause, nor was there evidence of target end-organ damage except for grade 1 Keith-Wagener-Barker retinopathy. The patient denied taking any prescription or over-the-counter medications. Hypertension is the most common disease-specific reason Americans visit a physician. Despite the risks associated with an elevated blood pressure (BP), there is still woefully low achievement of recommended BP goals. From 1991 to 1994, only 27.4% of hypertensive Americans aged 18 to 74 years had a BP <140/90 mm Hg, the current stated goal for most people with hypertension, and in those with diabetes, less than half that number (11%) were controlled to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI (JNC VI) recommended goal of <130/85 mm Hg.1 The present update will provide an overview of the evaluation and management of essential hypertension and help to guide clinicians in developing a management plan for a patient like the one described above. Taking a proper BP is an important first step in the diagnosis of hypertension.2 Using the proper cuff size with patients resting quietly and comfortably (with back support if seated) for at least 5 minutes before measurement, 2 or more readings separated by 2 minutes should be taken and averaged. Initial elevated BP readings should be confirmed on at least 2 subsequent visits over a period of 1 week or more. A value that is consistently ≥140/90 mm Hg is diagnostic in healthy patients; a value >130/80 mm Hg should be used for those with diabetes or kidney disease and proteinuria. Initial evaluation of the hypertensive patient focuses on the presence …

Increasing homocysteine levels and diabetic autonomic neuropathy

Objective: To determine if hyperhomocysteinemia is a risk factor for the development of diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic autonomic neuropathy (DAN). Background: Hyperhomocysteinemia and non-insulin-dependent diabetes mellitus (NIDDM) are both associated with premature vascular disease. Microvascular ischemia may be a risk factor for DSPN and DAN; therefore, the relationship of hyperhomocysteinemia to DSPN and DAN was investigated. Methods: Baseline neurological tests and homocysteine levels were determined in patients from a large prospective study of diabetic complications, the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Results: Total homocysteine (tHcy) was independently associated with DAN; for each 1 μmol/l increase in tHcy, there was a 7.1% increased risk of developing DAN ( P<0.05). There was no association between tHcy and DSPN. Conclusions: Hyperhomocysteinemia may be a risk factor for DAN but not for DSPN. This relationship may be related to differential small fiber injury. Further studies are needed to investigate this relationship between tHcy and DAN, specifically whether treatment of hyperhomocysteinemia may modify DAN.

Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes.

To assess whether ACE inhibitors are superior to alternative agents for the prevention of cardiovascular events in patients with hypertension and type 2 diabetes. This study is a review and meta-analysis of randomized controlled trials that included patients with type 2 diabetes and hypertension who were randomized to an ACE inhibitor or an alternative drug, were followed for > or =2 years, and had adjudicated cardiovascular events. A total of 4 trials were eligible. The Appropriate Blood Pressure Control in Diabetes (ABCD) trial (n = 470) compared enalapril with nisoldipine, the Captopril Prevention Project (CAPPP) (n = 572) compared captopril with diuretics or beta-blockers, the Fosinopril Versus Amlodipine Cardiovascular Events Trial (FACET) (n = 380) compared fosinopril with amlodipine, and the U.K. Prospective Diabetes Study (UKPDS) (n = 758) compared captopril with atenolol. The cumulative results of the first 3 trials showed a significant benefit of ACE inhibitors compared with alternative treatments on the outcomes of acute myocardial infarction (63% reduction, P < 0.001), cardiovascular events (51% reduction, P < 0.001), and all-cause mortality (62% reduction, P = 0.010). These findings were not observed in the UKPDS. The ACE inhibitors did not appear to be superior to other agents for the outcome of stroke in any of the trials. None of the findings were explained by differences in blood pressure control. Compared with the alternative agents tested, ACE inhibitors may provide a special advantage in addition to blood pressure control. The question of whether atenolol is equivalent to captopril remains open. Conclusive evidence on the comparative effects of antihypertensive treatments will come from large prospective randomized trials.

Improving the prognosis of diabetic patients: Evaluating the role of intensive versus moderate blood pressure control with selective angiotensin II receptor blocker (ARB) therapy

The ABCD (Appropriate Blood Pressure Control in Diabetes) and ABCD-2V (Part 2 with Valsartan) are prospective, randomised clinical trials which will provide important data on the impact of intensive vs. moderate blood pressure (BP) control on microvascular and macrovascular complications in normotensive and hypertensive patients with type 2 diabetes mellitus (DM). The ABCD trial was a five-year study that compared the effects of intensive vs. moderate BP control on the endpoints of nephropathy, retinopathy, neuropathy, and cardiovascular disease events using a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor as the primary antihypertensive agents. The recently published results of the hypertensive cohort of ABCD are reviewed herein. The follow-up study, ABCD-2V, is ongoing and was designed to compare intensive vs. moderate BP control on the same endpoints as the ABCD study, using the highly selective angiotensin II receptor blocker (ARB) valsartan as the primary antihypertensive agent. First results of ABCD-2V are expected in 2004. The baseline characteristics for the patients enrolled thus far in the hypertensive cohort of ABCD-2V are reviewed. These studies will provide insight into the role of intensive vs. moderate BP control in the management of normotensive and hypertensive patients with type 2 DM.

Treatment of diabetic patients with hypertension

This review attempts to highlight the potential of calcium-channel blockers in the prevention of sequelae of diabetes mellitus and hypertension in patients who have both disorders. Evidence-based medicine is driven by the results of randomized, clinical trials. Major contributions were therefore derived from post hoc analyses of the diabetic patients enrolled in placebo-controlled trials, such as Systolic Hypertension in the Elderly Program (SHEP), Systolic Hypertension in Europe (Syst-Eur), and Systolic Hypertension in China (Syst-China), and stepped-care blood-pressure-oriented trials, such as the Hypertension Optimal Treatment (HOT) and United Kingdom Prospective Diabetes Study (UKPDS). Several studies, such as the Fosiniprl; versus Amlodipine Cardiovascular Events Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD) Trial, have compared the relative merits of angiotensin-converting enzyme and calcium-channel blockers in preserving renal function and metabolic balance in diabetic patients with hypertension, but their publications focused on cardiovascular disorders, which were only secondary end points. On balance, the articles reviewed prove that dihydropyridine calcium-channel blockers score particularly well in the prevention of cardiovascular complications in diabetic patients with hypertension.

Antihypertensive therapy in type 2 diabetes: implications of the appropriate blood pressure control in diabetes (ABCD) trial

As the population ages, the incidence of type 2 diabetes will increase as will the incidence of concomitant vascular complications. Hypertension substantially increases the risk of cardiovascular disease in patients with diabetes. Results from the recent Appropriate Blood Pressure Control in Diabetes (ABCD) trial demonstrated an advantage of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) over a long-acting calcium antagonist (nisoldipine) with regard to the incidence of cardiovascular events over a 5-year follow-up period in hypertensive persons with type 2 diabetes. This trial was a prospective, randomized, blinded study comparing the effects of moderate blood pressure control (target diastolic pressure 80–89 mm Hg) with those of intensive control (target diastolic pressure 75 mm Hg) on the incidence and progression of diabetic vascular complications. The study also compared nisoldipine with enalapril as first-line antihypertensive therapy in terms of prevention and progression of complications of diabetes. In 470 hypertensive patients, the incidence of fatal and nonfatal myocardial infarctions was significantly (p = 0.001) higher among those receiving nisoldipine (n = 25) compared with those receiving enalapril (n = 5). Comparison with previous studies suggests that the difference observed between nisoldipine and enalapril resulted from a beneficial effect of enalapril rather than a deleterious effect from nisoldipine. Since these findings in the ABCD trial are based on a secondary endpoint, they require confirmation. Nevertheless, they suggest that ACE inhibitors should be the initial antihypertensive medication used in patients with type 2 diabetes and hypertension.

Calcium antagonists and the diabetic patient: a response to recent controversies

The results of 2 recently published studies have been interpreted as suggesting that calcium antagonists are unsafe for the management of hypertension in patients with diabetes. These 2 studies, the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD), showed that angiotensin-converting enzyme (ACE) inhibitors may be preferable to calcium antagonists for managing hypertension in diabetic patients; they do not, however, show any harm attributable to calcium antagonists. Indeed, results of the FACET study suggest that the combination of an ACE inhibitor and a calcium antagonist is effective antihypertensive therapy. This suggestion is supported by findings in the Systolic Hypertension in Europe (Syst-Eur) Study, which revealed outstanding benefits of either a calcium antagonist alone or a calcium antagonist combined with an ACE inhibitor among diabetic patients with hypertension. The premature termination of the hypertensive arm of the ABCD study was puzzling because, although 2 of 13 subgroups of 1 of the 5 possible secondary endpoints in this part of the trial were apparently favorably affected by the use of the ACE inhibitor rather than the calcium antagonist, such a finding was compatible with chance alone. If the results of the FACET and ABCD studies are considered in the context of the best available data arising from large randomized controlled trials, one may conclude that calcium antagonists are not harmful or contraindicated in hypertensive patients with diabetes and that the combination of an ACE inhibitor and a calcium antagonist is effective for the management of hypertension in diabetic patients.

Increased MI Risk with Nisoldipine in NIDD.

Despite the widespread use of calcium-channel blockers, there are lingering concerns about their putative association with increased cardiovascular risk. To address this controversial issue, investigators used data from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial, a prospective, randomized, blinded study that …

New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes.

Recent trials in hypertensive patients with type 2 diabetes reveal important differences in the risk for major cardiovascular events when individual agents are compared. In the Fosinopril Amlodipine Cardiovascular Events Trial (FACET), 380 patients with hypertension and type 2 diabetes were randomized to fosinopril or amlodipine and followed for up to 3.5 years to assess effects on serum lipids. Although both agents effectively controlled blood pressure, amlodipine caused a significantly greater decrease in systolic pressure. At the end of the trial, serum cholesterol, high-density lipoprotein cholesterol, triglycerides, HbA1c, serum glucose, plasma insulin, serum creatinine, and microalbuminuria were similar in both groups. The patients randomized to fosinopril were significantly less likely to experience the prospectively defined combined outcome of acute myocardial infarction (MI), hospitalized angina, or stroke compared to those randomized to amlodipine (RR 0.49; 95% CI 0.26-0.95). In the Appropriate Blood pressure Control in Diabetes (ABCD) trial, 470 patients with hypertension and type 2 diabetes who were randomized to long-acting nisoldipine had an adjusted sevenfold increased risk for acute MI compared to those randomized to enalapril (RR 7.0; 95% CI 2.3-21.4). In the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) trial, the patients with hypertension and above the median of HbA1c (> or =6.7%) randomized to isradipine had a threefold increased risk for major cardiovascular events compared to those randomized to hydrochlorothiazide (RR 2.81; 95% CI 1.09-7.26). These findings are supported by several observational studies. Therefore, evidence is emerging that angiotensin-converting enzyme inhibitors and low-dose diuretics may be more effective than calcium antagonists for prevention of cardiovascular events in hypertensive patients with diabetes or impaired glucose control.

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy

Previous studies have shown that the angiotensin-converting enzyme (ACE) gene polymorphism is associated with an increased risk of vascular disease in non-diabetic patients. The present study was conducted on 509 NIDDM patients who underwent a screening test to determine their ACE genotype for the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were correlated with the three ACE polymorphisms. The genotype was determined through polymerase chain reaction amplification of the angiotensin-converting enzyme polymorphism. The univariate relationship between the presence of the DD genotype with nephropathy as measured by urinary albumin excretion (UAE), and a history coronary artery disease (CAD) was then examined. Finally, a multiple model for each UAE and CAD was created so as to determine the independent effects of the presence of the DD genotype on each diabetic complication. Univariately, the presence of the DD genotype was associated with diabetic nephropathy. Furthermore, in a multiple model predicting diabetic nephropathy, the presence of the DD genotype was independently associated with diabetic nephropathy (odds ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the U.S. was independently associated with the presence of diabetic nephropathy and, therefore, may be potentially used as a marker for NIDDM patients at risk for developing diabetic nephropathy.

Associations of hypertension and complications in non-insulin-dependent diabetes mellitus

Hypertension is a common comorbidity with non-insulin-dependent diabetes mellitus (NIDDM). Data are somewhat inconsistent as to whether hypertension exacerbates diabetic complications in this population. Therefore, we examined the relationship between hypertension and vascular complications of NIDDM in the 950 patients enrolled in the prospective and randomized Appropriate Blood Pressure Control in Diabetes (ABCD) study. We found both systolic and diastolic hypertension to be associated with diabetic nephropathy ( P < .001) as well as with its macrovascular complications ( P < .05). Our present results also demonstrated that there was a significant relationship between hypertension and peripheral vascular disease ( P < .05), and left ventricular hypertrophy ( P < .001). There was, however, no apparent relationship between hypertension and diabetic neuropathy. Thus, arterial pressure may be a major determinant of complications in NIDDM.

Baseline characteristics of participants in the appropriate blood pressure control in diabetes trial

The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large, prospective, randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and of an angiotensin-converting enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations: a hypertensive one (diastolic blood pressure of⩾90.0 mm Hg at the time of randomization) and a normotensive one (diastolic blood pressure of 80.0–89.0 mm Hg at the time of randomization). A total of 950 men and women aged 40–74 years were randomized and are being followed for 5 years at a single center. There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population.