Effects of intensive blood pressure lowering on mortality and cardiovascular and renal outcomes in type 2 diabetic patients: A meta-analysis

Abstract

Background Previous studies have demonstrated that intensive blood pressure (BP) lowering treatment reduces the risk of all-cause mortality and provides greater vascular protection for patients with hypertension. Whether intensive BP lowering treatment is associated with such benefits in patients with type 2 diabetes mellitus remain unknown. We aimed to clarify these benefits by method of meta-analysis. Methods The PubMed, EMBASE, Science Citation Index and Cochrane Library databases were searched to identify randomized controlled trials (RCT) that fulfilled study inclusion criteria. Two investigators independently extracted and summarized the relevant data of the included trials. Random-effects model was applied to calculate the estimates of all effect measures. Results We included 16 RCTs and our meta-analysis showed that intensive BP lowering treatment vs less intensive BP lowering treatment resulted in significant reductions in the all-cause mortality risk [relative risk (RR), 0.82; 95% CI, 0.70–0.96], major CV events (RR, 0.82; 95% CI, 0.73–0.92, MI (RR, 0.86; 95% CI, 0.77–0.96), stroke (RR, 0.72; 95% CI, 0.60–0.88, CV death (RR, 0.73; 95% CI, 0.58–0.92) and albuminuria progression (RR, 0.91 95% CI, 0.84–0.98). However, intensive BP lowering treatment had no clear effect on non-CV death (RR, 0.97; 95% CI, 0.79–1.20), heart failure (HF) (RR, 0.88; 95% CI, 0.71–1.08) or end-stage kidney disease (ESKD) (RR, 1.00; 95% CI, 0.75–1.33). Subgroup analysis showed that the reduction in all cause-mortality was consistent across most patient groups, and intensive BP lowering treatment had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. However, the benefit differed in patients with different CV risk (≥10%: RR, 0.77, 95%CI, 0.64–0.91; <10%: RR, 1.04, 95%CI, 0.84–1.29; P hetero = 0.028). Conclusions Our data indicate that intensive BP lowering treatment provides greater benefits than less intensive treatment among patients with type 2 diabetes mellitus. Further studies are required to more clearly evaluate the benefits and harms of BP targets below those currently recommended with intensive BP lowering treatment.

Blood pressure control in older adults with hypertension: A systematic review with meta-analysis and meta-regression

“…Despite the methodological differences in the included studies, our meta-analysis is in agreement with findings of a recent meta-analysis [ 18 ] that showed significant reductions in CV outcomes in a hypertensive population (including hypertension with comorbidities). Our results also agree with previous systematic reviews [ 21 , 42 ] and the most recent meta-analyses [ 17 , 19 ] in people with diabetes, cardiovascular disease and chronic kidney disease. In contrast, Takami et al.…”

“…Our data were in contrast to previous studies that found low BP was associated with higher death rates, due to hypotensive effects, in the older population [ 37 , 38 ]. In hypertensive patients with diabetes or CVD risk, BP treatment has been shown to be effective in lowering the relative risk of CV events and all-cause mortality [ 17 , 19 , 21 ]. Interestingly, more recent studies [ 9 , 10 , 13 ] showed greater relative risk reduction for CV events possibly due to more aggressive BP treatment targets, replacing the placebo with a set target in the standard treatment group and more effective medication protocols.…”

“…Previous meta-analyses have shown that a reduction in systolic BP (<120–130 mmHg) could significantly reduce CVD risk [ [16] , [17] , [18] , [19] , [20] ] especially in patients with chronic kidney disease, vascular diseases or diabetes. In people with diabetes, intensive BP treatment offers greater vascular protection [ 21 ], a significant reduction in all-cause mortality, albuminuria progression and CV events [ 19 ] and significant risk reductions for MCEs [ 17 ]. In mixed populations, intensive BP treatment resulted in improved cardiovascular protection [ 18 ] and decreased heart failure risk [ 22 ].…”

Mechanisms Leading to Differential Hypoxia-Inducible Factor Signaling in the Diabetic Kidney: Modulation by SGLT2 Inhibitors and Hypoxia Mimetics

“…Similarly, the renal benefits of SGLT2 inhibitors cannot be ascribed to their modest action to lower blood pressure because even intensive control of blood pressure does not prevent serious renal events in type 2 diabetes. 3 SGLT2 inhibitors alleviate the increased intraglomerular filtration pressure that has been implicated in the genesis of diabetic nephropathy. Their inhibitory effects in the proximal renal tubule promote sodium delivery to the macula densa, which (through tubuloglomerular feedback) mitigates the afferent arteriolar vasodilatation produced by hyperglycemia.…”

Intensive blood pressure lowering: a practical review

“…Wang et al [ 22 ] aimed to clarify whether intensive BP lowering was associated with benefits in patients with type 2 diabetes mellitus. They included 16 RCTs in a meta-analysis comparing intensive vs. less intensive BP lowering and found that intensive BP lowering resulted in significant reductions in the all-cause mortality risk, MACE, MI, stroke, CV death, and the progression of albuminuria.…”