Aspects of blood pressure, lipid, and glycemic treatment.

Blood pressure treatment William Cushman described the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which had a total of 33,357 hypertensive participants, 36% of whom had diabetes, making it the largest study of blood pressure treatment in diabetes (1). Interestingly, 60% of the population studied satisfied criteria for the metabolic syndrome. In both the diabetic and nondiabetic subgroups, there was no difference in coronary heart disease (CHD) events or mortality between patients randomized to chlorthalidone, amlodipine, and lisinopril. Congestive heart failure (CHF) was less common with chlorthalidone than with the other agents. For those with fasting glucose 126 mg/dl at baseline, the mean glucose was 93 mg/dl at baseline, with levels increasing to 104 mg/dl with chlorthalidone, 103 mg/dl with amlodipine, and 101 mg/dl with lisinopril at 4 years. Similarly, diabetes incidence was highest with chlorthalidone at 11.6 vs. 9.8% with amlodipine and 8.1% with lisinopril. Including those persons who developed diabetes, and those with fasting glucose 126 mg/dl who had unrecognized diabetes, 39, 40, and 39% of persons in the three groups actually had diabetes. In each group, 4% had impaired fasting glucose (IFG) at levels of 110–125 mg/dl. The diabetic participants had 36% CVD prevalence, as opposed to 62% of the IFG and nondiabetic groups, based on the differing entry criteria for those with and without diabetes. Initial fasting glucose levels were 169, 116, and 91 mg/dl in the respective groups. Lisinopril did not lower systolic blood pressure as effectively as the two other agents, although it affected diastolic blood pressure similarly. Among persons with diabetes, at 2 years fasting blood glucose decreased 3 and 2 mg/dl with amlodipine and lisinopril, respectively, while increasing 6 mg/dl with chlorthalidone. In the IFG group, mean blood glucose increased from 116 mg/dl at baseline to 130, 123, and 116 mg/dl at 2 years and to 129, 130, and 117 mg/dl at 4 years, with chlorthalidone, amlodipine, and lisinopril, respectively. The incidences of diabetes among those with IFG were 44, 35, and 27% at 2 years and 39, 38, and 29% at 4 years, so that lisinopril was associated with a 25% lower relative risk of diabetes in this subset. For those with normal glucose at baseline, at both 2 and 4 years glucose levels were significantly higher with chlorthalidone, with higher diabetes incidence at both time points. For patients with IFG, amlodipine was associated with significantly worse outcome than with either chlorthalidone or lisinopril, with a 90% greater CVD risk and 40% higher CHF risk, and the CHF risk was 17% higher with lisinopril than with chlorthalidone. In persons with diabetes, no significant difference was seen between agents in CHD, all-cause mortality, stroke, or combined CVD. Cumulative mortality for hospitalized CHF patients was 50% at 5 years regardless of which drug was used, a prevalence that was five times greater than that in patients without CHF. Interestingly, and perhaps contributing to the unexpectedly unfavorable outcome with lisinopril, 29% of patients discontinued this agent at 5 years, as opposed to 20% of those treated with chlorthalidone and amlodipine. John M. Lachin (Rockville, MD) discussed the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up of 1,300 of the 1,441 persons enrolled in the Diabetes Control and Complications Trial (DCCT) for an additional 8 years after the mean of 6.5 years in the DCCT. During the trial, the control and intervention groups had mean HbA1c of 9 vs. 7%, with retinopathy progressing in 15 vs. 3% at 4 years and a 76% decrease in risk over 9 years among those in the primary intervention. The risk of retinopathy was greatest among those entering with the highest HbA1c and longest duration of diabetes, both among conventional and intensive treatment groups (2). The effects of glucose increase were long lasting, with each year of diabetes having greatest effect early in the course of the disease. The DCCT was closed in 1993, patients were enrolled in EDIC in 1994, and, after 1 year, HbA1c had fallen to 8.2% in the previous control group while rising to 8% in the previous intensive treatment group. However, after adjusting for previous retinopathy, 63% retinopathy risk reduction was seen in the latter group. For each 1% higher HbA1c during the DCCT, the risk of retinopathy progression during EDIC was 2.67-fold greater. For normoalbuminuric persons, the risk of new clinical albuminuria was 83% lower among those who had been in the intensively treated group. This phenomenon of “metabolic memory” suggests that a year of hyperglycemia experienced earlier in the course of a patient’s diabetes has greater effect earlier than one experienced later. Overall, the mean HbA1c during the DCCT explained 94–98% of renal and retinal complications during EDIC. Based on these studies, Lachin stated, a person whose HbA1c was 7% during the last 4 years of the DCCT but 9% thereafter would have a 1% annual risk of retinopathy progression, whereas a person whose HbA1c was 9% for the first 4 years and ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●