Diabetes Care. 2014 Feb;37(2):546-54.

Hyperglycemia and mortality among patients with coronary artery disease.

Ding D, Qiu J, Li X, Li D, Xia M, Li Z, Su D, Wang Y, Zhang Y, Zhang J, Lv X, Xiao Y, Hu G, Ling W.

Corresponding authors: Wenhua Ling, lingwh@mail.sysu.edu.cn.

 

Abstract

OBJECTIVE: Known diabetes is an independent predictor for mortality in coronary artery disease (CAD) patients; however, whether other glucose abnormalities are associated with death risk in CAD patients is unclear. The goal of this study was to examine the association between different glucose states and the risks of all-cause and cardiovascular disease (CVD) mortality among CAD patients.

RESEARCH DESIGN AND METHODS: The study cohort included 1,726 CAD patients who were 40-85 years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional hazards regression models were used to estimate the association of baseline glucose status with risk of mortality.

RESULTS: During a median follow-up of 3.1 years, 129 deaths were recorded, 109 of which were due to CVD. The multivariable-adjusted (age; sex; education; marriage; leisure-time physical activity; smoking; alcohol drinking; BMI; systolic blood pressure; total and HDL cholesterol; glomerular filtration rate; type, severity, duration, and treatment of CAD; history of heart failure; and use of antihypertensive, cholesterol-lowering, and antiplatelet drugs) hazard ratios in normoglycemia, impaired glucose regulation (IGR), newly diagnosed diabetes, and known diabetes were 1.00, 1.58 (95% CI 0.90-2.77), 2.41 (1.42-4.11), and 2.29 (1.36-3.84) for all-cause mortality and 1.00, 1.89 (1.01-3.54), 2.74 (1.50-5.01), and 2.73 (1.52-4.91) for CVD mortality. Assessing fasting plasma glucose only, impaired fasting glucose and newly diagnosed and known diabetes were also associated with increased risks of all-cause and CVD mortality compared with normoglycemia.

CONCLUSIONS: CAD patients with IGR, newly diagnosed diabetes, and known diabetes have increased risk of CVD mortality.

PMID: 24089546

 

SUPPLEMENTS:

Diabetes is one of the major public health burdens in the world and serves as a well-established risk factor for coronary artery disease (CAD). According to the International Diabetes Federation, more than 371 million people (8.3% of the population) have diabetes worldwide, and half of them are undiagnosed. The situation in China is severer. With rapid economic development and lifestyle changes that come along, the prevalence of diabetes increases to 9.7% of Chinese adults, and the undiagnosed rate is up to 60%, which far exceeds the average worldwide level.

As a primary contributor to CAD, diabetes affects about 50% CAD patients, while another 25% CAD patients endure impaired glucose regulation (IGR). It is well known that people with diabetes have a significantly increased premature mortality compared with non-diabetics, as well as a 2-4 times risk of developing  cardiovascular disease (CVD) which is presently the leading cause of death both in China and worldwide. However, whether people with undiagnosed diabetes or prediabetes status have higher risks for CVD and premature death has not been fully established. Some studies showed no association, on the other hand, some studies showed a positive association that disappeared after adjustment for covariates.  With regard to the secondary CVD risk, studies are few and inconsistent. Moreover, none of the existing cohorts are based on Chinese or Asian CAD populations. Previous evidence has shown that Western CAD patients generally have worse CVD risk profiles than Chinese patients, which include higher prevalence of hypertension, dyslipidemia, obesity and alcohol use. However, Chinese CAD patients’ total and CVD mortality is as high as that in Westerns. Thus, it is meaningful to focus on hyperglycemia with relationship to the secondary risk of Chinese CAD patients. The aim of this study was to evaluate the association of different glucose states with the risks of all-cause and CVD mortality among Chinese CAD patients.

Only a few studies have assessed the association between hyperglycemia (including known and newly diagnosed diabetes, as well as IGR and IFG) and death risk among CAD patients. The present study indicated that known diabetes, newly diagnosed diabetes and pre-diabetes (IGR or IFG), were independent risk factors of mortality among CAD patients. Several previous studies have confirmed that known diabetes is associated with a high risk of adverse outcome for CAD patients. However, regarding to newly diagnosed diabetes and IGR, previous findings were inconsistent. Displayed by spline plots, we found a J-shaped relationship between the baseline FPG and subsequent death of all-cause and CVD; the cutpoint of increase in the risk was apparent for glucose level which was below current diabetic threshold, even the IFG threshold. This finding was consistent with the previous Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe (DECODE) study. In their meta-analysis, there was a J-shaped relation between FPG and mortality of all-cause, CVD, and non-CVD among European general populations. And the thresholds of increase of risk were 5.3mmol/L for all-cause and 5.4 mmol/L for CVD. Thus, our study confirmed the prognostic significance of the current ADA recommendation for the lower IFG threshold in Chinese patients with CAD.

The present study also showed that in comparison with known diabetic CAD patients, the risk of death from all cause and CVD was a little higher in newly diagnosed diabetic patients. This might be because not all the newly diagnosed patients were patients with newly onset of diabetes. Part of them had diabetes for a period of time but undiagnosed, which was proven by Chinese high undiagnosed rate of diabetes. Lack of monitoring and control of glucose might partly explain the higher risk of mortality compared with known diabetic patients, 69% of whom took anti-diabetic drugs at baseline in our cohort. Moreover, our patients with newly diagnosed diabetes were severer with CAD and shared more harmful lifestyles. The rates of smoking and alcohol drinking were higher while the time of physical activity was less in patients with newly diagnosed diabetes.

Since IGR, IFG and newly diagnosed diabetes have been confirmed as independent risk factors of death in our study and several others, we need to pay attention to CAD patients with hyperglycemia, especially those with pre-diabetes and newly diagnosed diabetes. IFG and IGT have been proven as high risk factors of developing diabetes, and they are considered as intermediate stages in any form of diabetes process. In addition, subjects with IFG and IGT are also related to many traditional CVD risk factors, such as obesity, dyslipidemia and hypertension. Recent studies have shown that the onset of diabetes can be prevented or delayed in subjects with prediabetes through lifestyle intervention and treatment with oral hypoglycemic agents, while lifestyle intervention is more effective than drugs. Therefore, it is important to develop a screening strategy of glucose which is both practical and predictive to individuals who will benefit from early diagnosis and prevention of glucose abnormality. Our finding also raises the question whether directed glucose-lowering intervention might further improve clinical outcomes in CAD patients with hyperglycemia.

figure 1A

figure 1B

Figure 1. Multivariate-adjusted cumulative survival curves of all-cause (A) and CVD (B) mortality associated with both fasting and 2-hour glucose states. Adjusted for age, gender, education, marriage, leisure–time physical activity, smoking, alcohol drinking, type of CAD, severity of CAD, duration of CAD, treatment of CAD, history of heart failure, BMI, SBP, total cholesterol, HDL cholesterol, eGFR, use of antihypertensive drugs, use of cholesterol-lowering drugs, and use of antiplatelet drugs. The line of newly diagnosed diabetes overlapped with the line of known diabetes in Figure 1B.

 

Figure 2A

Figure 2B

Figure 2. Spline plots displaying the risk all-cause (A) and CVD (B) mortality over the range of fasting plasma glucose.

 

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