Benefits of Tight Blood Pressure Control in Diabetic patients with Hypertension,2011, June 03, 嚴逢杰醫師,Diabetes Care, Volume 34, Supplement 2, May 2011,Diabetic patients are characterized by a significantly higher risk of CV events compared with nondiabetic individuals, with diabetes itself being considered a CVD equivalent. (1-4) Observational data from UKPDS reported a continuous positive correlation between the level of SBP and the risk of developing macro- and microvascular complications in T2D pts, without any evidence of BP threshold level. (5) With known synergistic interaction of hypertension and diabetes as CV risk, optimal BP control is particularly important in hypertensive pt with DM. (7-11),The UKPDS was formally close in 2007, i.e., 30 years after its outset(開端）, thus being one of the longest trials ever made. The main aim of this study was to establish whether, in pt with T2D, intensive glycemic control might reduce the risk of vascular complications, and its result have profoundly influenced the management of T2D. (12-14) The Hypertension in Diabetes Study (HDS), embedded in the UKPDS in 1987, confirmed that hypertension is a major risk factor for CVD in T2D pt (16-18) and addressed the importance of a tight BP control in hypertensive pt with T2D(19).,Legacy Effect of Earlier Glucose Control,The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. N Engl J Med 2005;353:2643-2653,Cumulative Incidence of the First of Any of the Predefined Cardiovascular Disease Outcomes (Panel A) and of the First Occurrence of Nonfatal Myocardial Infarction, Stroke, or Death from Cardiovascular Disease (Panel B),42%,57%,Legacy Effect,NEJM 2008; 359:1565-76,BMJ 1998;307: 703-13,Median duration of follow-up was 8.4 yrs. Tight vs conventional: 143/82 vs 154/88 mmHg,DM related events 24,DM related death 32,Microvascular 37,Stroke 44%,Posttrial f/u median duration: 8 yrs,No Legacy effect,Possible role of suboptimal BP lowering,Although prospective studies have showed that small reductions in BP reduce the CV events, the BP target of 150/85 mmHg considered for the tight BP control was by far above the current BP target of 130/80 in all major guideline. (29-32) Subsequent studies have assess the benefit associated with lower BP targets, however, no extended follow-up was conducted in any of them. (34-38),Influence of previous history of diabetes and delayed start of antihypertensive treatment,The HDS started 10 years after the original study. Therefore, the pt in the HDS were not actually newly diagnosed. During these 10 yrs, additional irreversible organ damage has likely developed, leading to a higher level of CV risk. A recent systemic review comparing the reductions in CV events, including pt with different baseline of CV risk, showed that the duration of disease with regard to time treatment started may influence outcome. Once organ damage is advanced, a high incidence of CV events persisted despite intensive BP lowing ( ceiling effect) (39). Finally, the importance of an early start of tx to optimize pt protection was suggested.,Factorial design of the study and impossibility to control for the effects of background interventions,When posttrial follow-up started, the median value of HbA1C at baseline was significantly higher in the tight control group than in the less tight control group. ( 8.3% vs 7.5%). Because the data from the main study and from HDS were analyzed independently following a factorial design, it was not possible to control for the effect of potential confounders, such as glycemic level.,Use of older less efficacious antihypertensive agents with adverse effects on glucose homeostasis,61% of pts in the tight control group were on 2 or more antihypertensive agents (compared with 36% in the less tight control group), a greater use of thiazide diuretics in tight control group could not be ruled out. Thus, its likely that the adverse metabolic effects reported for both atenolol and thiazide diuretics developed, as further suggested by the significant increases in mean glucose levels (1.0 vs 0.7 mmlo/L) and in body weight (2.3 vs 0.5kg).,Role of a shorter median time of randomized interventions in HDS,The randomized antihypertensive intervention in the HDS was only conducted during a median of 4 years. Although this was enough for benefits in CV outcomes in the short term, it was probably not long enough for tight BP control for confer a protecting legacy effect.,Small differences in BP between tight and less tight BP control,The difference between mean BP levels achieved over the 4 years of the randomized intervention for the tight and less tight BP control was relatively small ( 143/82 vs 154/88 mmHg), and this might have contributed to the lack of differences.,Absence of BP legacy or only a time-to-effect relationship between BP control and CV outcome?,