Blood pressure and cardiovascular disease risk in the Veterans Affairs Diabetes Trial

OBJECTIVE

Blood pressure ranges associated with cardiovascular disease (CVD) events in advanced type 2 diabetes are not clear. Our objective was to determine whether baseline and follow-up (On-Study) systolic blood pressure (SBP), diastolic blood pressure (DBP), and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial (VADT).

RESEARCH DESIGN AND METHODS

Participants in the VADT (n = 1,791) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in standard and intensive glycemic treatment groups. Blood pressure levels of all subjects at baseline and On-Study were analyzed to detect associations with CVD risk. The primary outcome was the time from randomization to the first occurrence of myocardial infarction, stroke, congestive heart failure, surgery for vascular disease, inoperable coronary disease, amputation for ischemic gangrene, or CVD death.

RESULTS

Separated SBP ≥140 mmHg had significant risk at baseline (hazards ratio HR] 1.508, P < 0.001) and On-Study (HR 1.469, P = 0.002). DBP <70 mmHg increased CVD events at baseline (HR 1.482, P < 0.001) and On-Study (HR 1.491, P < 0.001). Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP <70 mmHg at baseline (HR 1.785, P = 0.03) and On-Study (HR 2.042, P = 0.003) and nearly all SBP with DBP <70 mmHg.

CONCLUSIONS

Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension. Increased risk with DBP <70 mmHg, even when combined with SBP in guideline-recommended target ranges, supports a new finding in patients with type 2 diabetes. The results emphasize that DBP <70 mmHg in these patients was associated with elevated CVD risk and may best be avoided.Based on results of recent interventional trials (1–3), the question of whether or not intensive glucose control significantly reduces the risk of cardiovascular disease (CVD) in all patients with type 2 diabetes remains controversial. It may be beneficial in subgroups of these patients when severe hypoglycemia is avoided. Blood pressure (BP) control is consistently correlated with CVD events in studies of risk factors in type 2 diabetes. In the UK Prospective Diabetes Study, BP control was twice as effective as glucose control in preventing any diabetes end points (4,5). The Hypertension Optimal Treatment (HOT) study and the Appropriate Blood Pressure Control in Diabetes (ABCD) trial support improved BP control as a significant CVD event preventive factor in patients with diabetes (6–8). Both the American Diabetes Association (ADA) and the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommend treatment of BP in patients with diabetes to a target of <130/<80 mmHg (9,10). Current evidence supports a systolic blood pressure (SBP) level of <140 mmHg, but there is sparse information to guide physicians as to how far the SBP and diastolic blood pressure (DBP) can be lowered safely and whether lower BP levels might be associated with increased risk. We analyzed the BP data collected during the Veterans Affairs Diabetes Trial (VADT) to learn whether specific levels of BP in patients with type 2 diabetes predict CVD events.The VADT is a 20-center 1,791-patient prospective study of intensive versus standard glucose treatment in patients with suboptimal responses to maximum oral agents or insulin. The main objective was to assess the benefit of intensive glucose control for up to 7 years on CVD events in patients with advanced type 2 diabetes. Other objectives included the assessment of the effects on microvascular and neurological complications, cognitive function, quality of life, and cost-effectiveness. BP, lipids, diet, and lifestyle were treated identically in both arms. By improving BP control in an identical manner in both glucose arms, VADT excluded the effect of BP differences in CVD events between treatment arms and reduced the overall risk of macrovascular complications during the trial. The initial results were published recently (1).