High Density Lipoprotein Cholesterol and Outcame in Coronary Heart Disease: an Intriguing Relationship

Purpose: As originally demonstrated by the Framingham Study, high density lipoprotein (HDL) cholesterol levels are inversely associated with cardiovascular risk. In the present study, we investigated the effect of different levels of HDL cholesterol on the outcome of patients with known coronary heart disease (CHD). Methods: We prospectively examined 2322 consecutive patients (age 67±10 years, 79% male) with chronic CHD, defined by a >50% coronary stenosis and/or a previous myocardial infarction (MI). HDL cholesterol levels were low (<35 mg/dL) in 736 patients (32%), normal (35-60 mg/dL) in 1464 (63%), high (>60 mg/dL) in 122 (5%). Results: During follow-up (median 46 months), 223 patients (9.6%) developed a cardiac event: cardiac death in 143 patients and non-fatal MI in 80. As expected, cardiac event-free survival was lower in patients with low compared to normal HDL cholesterol (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.5 to 2.6, p <0.0001). Surprisingly, event-free survival was also lower in patients with high HDL compared to normal HDL cholesterol (HR 1.78, 95% CI 1.03 to 2.87, p = 0.039). The prognostic impact of low HDL cholesterol persisted (p <0.0001) after adjustment for age, sex, diabetes mellitus, left ventricular systolic function, extent of coronary stenoses, LDL cholesterol, triglycerides, complete blood count, thyroid and renal function. Conversely, the impact of elevated HDL cholesterol disappeared (p =0.40) after adjustment for age, body mass index, thyroid dysfunction and left ventricular ejection fraction. Despite being less frequently male (p <0.001), obese (p <0.05) and diabetic (p < 0.05) patients with elevated HDL cholesterol were 3 years older than those with normal HDL and 5 years older than those with low HDL cholesterol (p <0.0001). Conclusions: Although elevated HDL cholesterol is not associated with cardiac event-free survival at multivariate analysis, patients with elevated HDL cholesterol develop cardiac events similarly to those with low HDL, but at a more advanced age.