Swedish Study Indicates LDL Cholesterol Not a Good Marker of Cardiovascular Risk in Type 1 Diabetes

During the President’s Oral Session at the American Diabetes Association’s 74th Scientific Sessions, Christel Hero, MD, of Sahlgrenska University Hospital in Gothenburg, Sweden, presented data from a major study exploring risk factors for development of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D).

Hero said, “Patients with type 1 diabetes are at high risk of cardiovascular disease. While high levels of low-density lipoprotein (LDL) are an important risk factor for CVD in the general population and in type 2 diabetes, less is known about the risk of LDL levels in patients with type 1 diabetes. The aim of this study was to assess both LDL levels and the ratio of total cholesterol to high-density lipoprotein (HDL) as predictors of cardiovascular disease in type 1 diabetes patients and to evaluate their risk at different levels of LDL and different total cholesterol-to-HDL ratios.”

More than 30,000 patients with type 1 diabetes ranging in age from 18 to 79 years were included in the study from 2003 to 2006 and followed for a mean period of 7.2 years. Mean age of the study participants was 46 years with a mean diabetes duration of 20 years and mean HbA1c level of 8%. Their mean LDL was 2.7 mmol/L and mean TC:HDL ratio was 3.2. Slightly more than one-fourth of the participants (n= 8,172) were on some type of lipid-lowering medication. The group on medication was older, had a longer diabetes duration, and 24% of them had a history of CVD. Nearly one-third of the overall group (n=9,324) was 40 years or older with at least one CVD risk factor.

Researchers recorded fatal or non-fatal CVD events, including acute myocardial infarction, unstable angina, stroke, coronary artery bypass surgery and percutaneous coronary intervention, and peripheral vascular disease.

There were 14.6 CVD events/1000 person years (py) in the group of patients who were not on lipid-lowering medication and 52.3 events/1000 py in patients who were taking lipid-lowering medication. Cox regression analyses were performed with LDL level and TC:HDL ratio as predictors using fatal/nonfatal CVD as outcome, along with adjustments for other CVD risk factors. Adjusted hazard ratios (HRs) for CVD per 1 mmol/L increase in LDL were 1.03 (95% CI; 0.99 to 1.08) in all participants, 1.07 (95% CI; 1.00 to 1.14) in patients without lipid-lowering medication, and 1.04 (95% CI; 0.98 to 1.1) in patients with treatment.

All HRs were non-significant. Adjusted HRs for CVD per 1 unit increase in TC:HDL ratio were 1.08 (95% CI; 1.04 to 1.12) in all participants, 1.11 (95% CI; 1.05 to 1.17) in patients without lipid-lowering medication, and 1.08 (95% CI; 1.03 to 1.13) in patients with treatment.

All p-values were <0.01.

Risk of CVD was also assessed in octiles of LDL (reference of LDL 2.5 to 2.7). Compared to reference-only patients without lipid-lowering treatment, only the highest octile (LDL >3.6 mmol/L) showed a significantly higher risk,with HR of 1.24 (95% CI; 1.01 to 1.51).

“In our study, LDL level was not a significant predictor of cardiovascular disease in type 1 diabetes apart from in patients in the highest octile not treated with lipid-lowering medication. However, the ratio of total cholesterol to HDL was a significant predictor for CVD in all groups. The total cholesterol to HDL ratio seems to be a more reliable marker for risk in type 1 diabetes,” Hero said.

She also referenced the ADA’s January 2014 statement on diabetes care, primary prevention, statins, and LDL level, saying, “The guidance is that for lower-risk type 1 diabetes patients, that is, those without overt cardiovascular disease and under 40 years of age, physicians should consider statin therapy in addition to lifestyle therapy if LDL remains above 100 mg/dL, with a goal of LDL less than 100 mg/dL. We saw no support for an LDL treatment target of 100 mg/dL.”

In conclusion, Hero said, “LDL is not the best predictor of CVD in type 1 diabetes. However, the ratio of total cholesterol to HDL is a significant predictor for CVD in type 1 diabetes patients not using lipid-lowering drugs. The ratio of total cholesterol to HDL is a more reliable marker for risk when considering primary prevention.”