Ratio of Total Cholesterol to HDL-C is a More Relevant CV Risk Marker in T1DM

Summary

This article presents results from a large observational study in patients with type 1 diabetes mellitus (T1DM) that assessed cardiovascular disease (CVD) risk predictors and showed that low-density lipoprotein cholesterol (LDL-C) was not a good marker of CV risk [Hero C et al. ADA 2014 (oral session 381-OR)].

  • Diabetes Mellitus
  • Diabetes & Endocrinology Clinical Trials
  • Lipid Disorders
  • Endocrinology
  • Diabetes & Metabolic Syndrome
  • Diabetes Mellitus
  • Diabetes & Endocrinology Clinical Trials
  • Lipid Disorders

Christel Hero, MD, Sahlgrenska University Hospital, Gothenburg, Sweden, presented results from a large observational study in patients with type 1 diabetes mellitus (T1DM) that assessed cardiovascular disease (CVD) risk predictors and showed that low-density lipoprotein cholesterol (LDL-C) was not a good marker of CV risk [Hero C et al. ADA 2014 (oral session 381-OR)].

In the general population and in patients with type 2 diabetes mellitus (T2DM), elevated LDL-C is a well-known marker of CVD. Patients with T1DM are at high risk for CVD, but less is known about the association of CVD and LDL-C in these patients. The Standards of Medical Care in Diabetes—2014 [American Diabetes Association. Diabetes Care 2014] recommends statin therapy in addition to lifestyle therapy if LDL-C remains > 100 mg/dL in patients at low risk (no overt CVD and < 40 years old) or in those with multiple CVD risk factors without prior CVD.

The objective of this study was to evaluate LDL-C and the ratio of total cholesterol (TC) to HDL-C (TC:HDL-C) as predictors of CVD in patients with T1DM and to evaluate CVD risk at different levels of LDL-C. This analysis from the National Diabetes Register in Sweden included 30,778 patients, who were aged 18 to 79 years, identified between 2003 and 2006, and followed for a mean of 7 years. Mean patient age was 46 years, and mean duration of T1DM was 20 years. The outcomes evaluated were fatal and nonfatal CVD (acute myocardial infarction, unstable angina, percutaneous coronary intervention and coronary artery bypass graft, stroke, and peripheral vascular disease). Patients were divided into 2 groups by use of lipid-lowering medication (n = 22,608) or not (n = 1973), and they were further subdivided. Two subgroups of patients were also analyzed: those not taking lipid medication and ≥ 40 years with one CVD risk factor (n = 9324) and those taking lipid medication with a history of CVD (n = 1973). At baseline, the patients on lipid-lowering therapy were older, had a longer duration of diabetes, more frequently took an antihypertensive medication, and had a lower mean estimated glomerular filtration rate (eGFR; 75 mL/minute/m2), and more (24%) had a history of CVD.

Cox regression analyses were performed with LDL-C and TC:HDL-C as predictors of fatal and nonfatal CVD outcomes, adjusted for traditional CVD risk factors and treatment.

CVD events during follow-up are shown in Table 1. Two-thirds of patients with a history of CVD had a new event within 7 years. In the subgroup of patients > 40 years with one CVD risk factor, the risk was substantially higher for a new CV event (21%) in 7 years.

Table 1.

Proportion of Cardiovascular Disease Events During Follow-Up

In patients not on lipid-lowering therapy, the risk of a CVD event was increased for each 1 mmol/L increase in LDL-C (HR, 1.08; 95% CI, 1.01 to 1.11; p = .02) in the overall group and in the patients ≥ 40 years with one additional CVD risk factor (HR, 1.08; 95% CI, 1.01 to1.15; p = .03). When these patients were divided into octiles, there was no significant difference. For patients on lipid-lowering therapy, no significant difference was found for LDL-C as a continuous variable or by octiles.

There was, however, a strong correlation between CVD and the TC:HDL-C ratio per 1 unit increase in patients not on lipid-lowering therapy (HR, 1.08;95% CI, 1.03 to 1.14; p< .001) in the overall group and in the patients ≥ 40 years with one additional risk factor (HR, 1.15; 95% CI, 1.09 to 1.21; p< .001). There was a linear relationship between increasing TC:HDL-C ratio and CVD risk.

In patients taking lipid-lowering medication, there was a weaker, but still statistically significant, correlation between the TC:HDL-C ratio and the risk of CVD overall (HR, 1.06; 95% CI, 1.01 to 1.11; p = .02).

In summary, LDL-C was not the best predictor of CVD risk in patients with T1DM. The results of this study do not provide support for an LDL-C treatment goal of 100 mg/dL in patients with T1DM. The ratio of TC:HDL-C was, however, a significant predictor for CVD in patients not taking lipid-lowering medications. Furthermore, the ratio of TC:HDL-C was a more relevant risk marker for primary prevention in T1DM.

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