Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study

Abstract

Background This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. Methods This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). Results There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1–3 (Q1–3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. Conclusion This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677

Associations between continuous glucose monitoring-derived metrics and arterial stiffness in Japanese patients with type 2 diabetes

“…There were no differences in baPWV between males and females (p = 0.508) (Table 1 ). On the other hand, the percentage of smokers was lower in the high arterial stiffness group than in the low arterial stiffness group, consistent with a previous study [ 13 ]. Although smoking is a risk factor for CVD, previous data regarding the association between smoking and arterial stiffness are inconclusive [ 12 , 13 , 26 ].…”

“…On the other hand, the percentage of smokers was lower in the high arterial stiffness group than in the low arterial stiffness group, consistent with a previous study [ 13 ]. Although smoking is a risk factor for CVD, previous data regarding the association between smoking and arterial stiffness are inconclusive [ 12 , 13 , 26 ]. In a multivariate analysis that included potential conventional risk factors, neither gender nor smoking status was significantly associated with either baPWV or high arterial stiffness (data not shown), consistent with previous studies [ 12 , 26 ].…”

“…On the other hand, the percentage of smokers , systolic blood pressure, total cholesterol, HDL cholesterol, logarithm of triglycerides, serum uric acid, estimated glomerular filtration rate, logarithm of urinary albumin excretion, presence of diabetic retinopathy, smoking status (never smoker, previous smoker, or current smoker), use of insulin therapy, use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, use of statins, and use of anti-platelet agents CI: confidence interval; CV: coefficient of variation; FLP-CGM: FreeStyle Libre Pro continuous glucose monitoring; HBGI: high blood glucose index; IQR: interquartile range; LBGI: low blood glucose index; MAGE: mean amplitude of glycemic excursion; MODD: mean of daily differences; SD: standard deviation; TAR: time above range; TBR: time below range; TIR: time in range was lower in the high arterial stiffness group than in the low arterial stiffness group, consistent with a previous study [13]. Although smoking is a risk factor for CVD, previous data regarding the association between smoking and arterial stiffness are inconclusive [12,13,26]. In a multivariate analysis that included potential conventional risk factors, neither gender nor smoking status was significantly associated with either baPWV or high arterial stiffness (data not shown), consistent with previous studies [12,26].…”

“…To assess arterial wall stiffness, brachial-ankle pulse wave velocity (baPWV) is a noninvasive parameter that is often used clinically. It is useful for evaluating the state of atherosclerosis and predicting CVD or mortality in patients with type 2 diabetes [ 12 , 13 ]. However, the relationship between CGM-derived metrics and arterial stiffness has not yet been fully clarified.…”

Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial

“…Arterial stiffness is one of the earliest detectable signs of functional and structural changes in the vascular wall. baPWV, an established quantitative indicator of arterial stiffness, is linked to CV risk factors [ 31 , 32 ] and is a promising predictor of future CV events independent of conventional CV risk factors [ 29 , 33 – 39 ]. However, the effect of SGLT2 inhibitors on the progression of baPWV has not yet been completely elucidated.…”