Thresholds of risk factors for ischemic stroke in type 2 diabetic patients with and without albuminuria—A non-linear approach
Introduction
Type 2 diabetes is a highly heterogeneous condition with multiple risk factors and complications including stroke [1], [2]. Old age, high BP, smoking and hyperglycaemia are firmly established risk factors of stroke [3], [4], [5], [6] although the risk association between obesity and stroke remains to be clarified [7], [8], [9]. Albuminuria is a powerful predictor for cardiovascular diseases including stroke in both diabetic and non-diabetic populations [10]. There are now clinical and experimental data supporting albuminuria as a marker of endothelial dysfunction [11]. Prospective data have also shown that HbA1c, BP and BMI are promoters of albuminuria [12]. On the other hand, albuminuria can lead to progressive increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels which can increase the risk of coronary heart disease (CHD) [13]. Taken together, these data suggest that different causal factors may initiate the onset and progression of albuminuria while the latter can increase the risk of cardiovascular diseases independently or by promoting other risk factors.
In many epidemiological studies, the linear nature of these risk associations is often presumed although this has never been well demonstrated in literature. Confirming or refuting the linearity of these relationships have important therapeutic implications in light of ongoing debates on the target level to achieve and the threshold value to commence intervention. These questions cannot be easily addressed in a clinical trial whose primary objective is to examine the efficacy of a treatment, and often entails multiple exclusion criteria.
In this study, we aim to firstly, clarify whether these risk relationships exhibit non-linearity and threshold and secondly, whether these relationships are altered in the presence or absence of albuminuria.
Section snippets
Participants
The Prince of Wales Hospital is a regional hospital which serves a population of 1.2 million people. The Hong Kong Diabetes Registry established in 1995 enrols 30–50 ambulatory diabetic patients each week. The referral sources included general practitioners, community clinics, and other specialty clinics and patients discharged from hospitals. Patients discharged from hospital within 6–8 weeks prior to assessment accounted for less than 10% of all enrolments. The 4-h assessment of complications
Characteristics of study population
At enrolment, the median age of the cohort was 57 years (interquartile range [IQR]: 46–67 years) and had a median disease duration of 5 years (IQR: 1–11 years). The total follow-up time was 5.36 (IQR: 2.88–7.75) years. 2.64% (106) of the patients without albuminuria developed incident IS while 7.02% (208) of albuminuric patients developed incident IS. The incidence of IS was 4.78 (95%CI: 3.87–5.69) per 1000 person years in the non-albuminuric group and 14.01 (95%CI: 12.12–15.90) per 1000 person
Discussions
Using a relatively novel spline analysis, we have demonstrated non-linearity and thresholds of BMI, SBP, Hb and eGFR for IS in type 2 diabetes (Fig. 1). If the points at which IS risk started to increase or decrease rapidly are chosen as the threshold points, the respective values are 24 kg/m2 for BMI, 14 g/dl for blood Hb, 135 mmHg for SBP and 115 ml/min per 1.73 m2 for eGFR. In our confirmatory analysis, the thresholds of BMI and Hb are valid in the non-albuminuric group while the thresholds of
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