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1.  Lipid control and use of lipid-regulating drugs for prevention of cardiovascular events in Chinese type 2 diabetic patients: a prospective cohort study 
Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients.
In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD.
The multivariate-adjusted HR (95% confidence interval) of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L) was 1.36 (1.08 - 1.71), compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol (≥ 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in patients with metabolic syndrome [(HR = 0.58(0.42--0.80)].
In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.
PMCID: PMC3004819  PMID: 21092182
2.  Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients - a longitudinal observational study 
The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes.
This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005.
Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment.
In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high.
PMCID: PMC2777137  PMID: 19878541
3.  Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus 
There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM.
7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset.
During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m2) + 0.1363 × HbA1c(%) + 0.9915 × Log10(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S0(5)EXP{0.9744 × (Risk Score - 2.3961)}. Where S0(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up.
The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.
PMCID: PMC2377240  PMID: 18430204
4.  Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry 
Glycated haemoglobin (HbA1c), blood pressure and body mass index (BMI) are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD) may influence the effects of other risk factors on coronary heart disease (CHD).
A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings.
Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L.
In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.
PMCID: PMC2219954  PMID: 18053157

Results 1-4 (4)