Decreased peripheral perfusion measured by perfusion index is a novel indicator for cardiovascular death in patients with type 2 diabetes and established cardiovascular disease

www.nature.com/scientificreports OPEN Decreased peripheral perfusion measured by perfusion index is a novel indicator for cardiovascular death in patients with type 2 diabetes and established cardiovascular disease Hiroshi Okada1*, Muhei Tanaka2, Takashi Yasuda3, Yuki Okada1, Hisahiro Norikae4, Tetsuya Fujita4, Takashi Nishi4, Hirokazu Oyamada5, Tetsuro Yamane6 & Michiaki Fukui2 Cardiovascular disease (CVD) is still the major cause of mortality in patients with type 2 diabetes. Despite of recent therapies, mortality and resources spent on healthcare due to CVD is still important problem. Thus, appropriate markers are needed to predict poor outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for cardiovascular death in patients with type 2 diabetes and established CVD. This retrospective cohort study included 1080 patients with type 2 diabetes and history of CVD recruited from the outpatient clinic at Matsushita Memorial Hospital in Osaka, Japan. Peripheral perfusion is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. The median age and PI values were 74 years (range: 67–79 years) and 2.6% (range: 1.1–4.3%), respectively. During follow-up duration, 60 patients died due to CVD. The adjusted Cox regression analysis demonstrated that the risk of developing cardiovascular death was higher in the first quartile (Hazard ratio, 6.23; 95% CI, 2.28 to 22.12) or second quartile (Hazard ratio, 3.04; 95% CI, 1.46 to 6.85) of PI than that in the highest quartile (fourth quartile) of PI. PI (per 1% decrease) was associated with the development of cardiovascular death (Hazard ratio, 1.39; 95% CI, 1.16 to 1.68). PI could be a novel indicator of cardiovascular death in patients with type 2 diabetes and established CVD. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in patients with type 2 diabetes, and several risk factors including smoking, hypertension and dyslipidemia have been shown to accelerate the progression of C VD1,2. Despite of advances of diabetic therapies, there are large residual risks of CVD in patients with type 2 diabetes. Previous studies have reported the signification of peripheral flow in the early phase of critical illnesses3–6. It has been suggested that microcirculatory alterations are stronger predictors of poor outcome than hemodynamic flow5. The peripheral perfusion index (PI) is the ratio of pulsatile blood flow to non-pulsatile blood flow in the monitored tissue and has been shown to reflect changes in peripheral p erfusion7–9. A PI of 1.4 has been suggested to be correlated with low peripheral perfusion in critically ill patients7. Moreover, low value of PI was associated with adverse outcomes in the early phase of critical i llnesses9,10. However, there are no studies which reported the association between PI and the development of cardiovascular death in patients with type 2 1 Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, 5‑55 Sotojima‑cho, Moriguchi 570‑8540, Japan. 2Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. 3Department of Nephrology, Matsushita Memorial Hospital, Moriguchi, Japan. 4Department of General Affairs, Matsushita Memorial Hospital, Moriguchi, Japan. 5Department of Gastroenterology, Matsushita Memorial Hospital, Moriguchi, Japan. 6Department of Surgery, Matsushita Memorial Hospital, Moriguchi, Japan. *email: Scientific Reports | (2021) 11:2135 | https://doi.org/10.1038/s41598-021-81702-w 1 Vol.:(0123456789) www.nature.com/scientificreports/ n (male/female) 1080 (774/306) Age (years) 74 (67–79) Duration of diabetes (years) 7.5 (4–12) Body mass index (kg/m2) 24.6 (22.1–27.4) Systolic blood pressure (mmHg) 131 (117–143) Diastolic blood pressure (mmHg) 72 (61.3–82) Heart rate (beat per minutes) 75 (66–86) Hemoglobin A1c (%) 6.8 (6.3–7.7) Total cholesterol (mg/dl) 170 (146–203) Low-density lipoprotein cholesterol (mg/dl) 94.2 (68.2–121.15) Triglycerides (mg/dl) 116 (87–166) Uric acid (mg/dl) 5.5 (4.4–6.8) Creatinine (mg/dl) 0.96 (0.79–1.40) Smoking status (never/past/recent) 448/234/398 Hypertension (−/ +) 298/782 History of CVD (angina or myocardial infarction/stroke/peripheral artery disease) 765/298/161 Previous revascularization history (−/ +) 595/485 Perfusion index (%) 2.6 (1.1–4.3) Anti-platelet therapies (−/ +) 153/927 Renin-angiotensin system inhibitor (−/ +) 484/596 Glucagon-like peptide-1 agonists (−/ +) 984/116 Sodium-glucose cotransporter 2 inhibitor (−/ +) 983/97 Statin (−/ +) 476/604 Table 1.  Characteristics of patients. Data are expressed as the median (interquartile range) or absolute number. CVD, cardiovascular disease. diabetes in clinical care setting. Therefore, we aimed to assess the association between PI and the development of cardiovascular death and the association between PI and cardiovascular death or recurrent cardiovascular events in patients with type 2 diabetes and established CVD. Results The characteristics of all 1080 patients enrolled in this study are shown in Table 1. The average duration of follow up was 871 ± 265 days. The median age and PI values were 74 years (range: 67–79 years) and 2.6% (range: 1.1–4.3%), respectively. Sixty patients died due to cardiovascular death during study period (Quartile 1, 2, 3 and 4; 32,14,10 and 4, respectively). Cardiovascular death included 11 myocardial infarction, 44 heart failure, and 5 stroke during study period. One hundred and ninety-six patients developed the recurrent cardiovascular events during study period (Quartile 1,2,3 and 4; 86, 48, 37 and 25, respectively). Four patients developed myocardial infarction, 16 patients developed stroke, 120 patients received revascularization for angina and 56 patients received revascularization for peripheral artery disease (PAD). Patients with the development of cardiovascular death were older (P = 0.03) than those without at baseline. Their average SBP (P = 0.02) and serum creatinine (P < 0.0001) were higher than those without at baseline. Patients with the development of cardiovascular death had longer duration of diabetes than that without at baseline (P = 0.02). PI or total cholesterol was lower at baseline in patients with the development of cardiovascular death than that without (P < 0.0001 or P = 0.0007). We found negative correlation between PI and age (r = − 0.15, P < 0.0001), heart rate (r = − 0.15, P < 0.0001) or serum creatinine (r = − 0.14, P < 0.0001). We found positive correlation between PI and body mass index (BMI) (r = 0.11, P = 0.0002). Table 2 reports characteristics of the study participants at the baseline according to quartiles of PI. The proportion of male was higher in highest quartile of PI (quartile 4) than those in in the other quartiles. Participants in the highest quartile of PI (quartile 4) was (...truncated)