Physicians' Academy for Cardiovascular Education

Isolated low levels of HDL-C associated with increased risk of CHD

News - Nov. 10, 2011

Isolated Low Levels of High-Density Lipoprotein Cholesterol Are Associated With an Increased Risk of Coronary Heart Disease - An Individual Participant Data Meta-Analysis of 23 Studies in the Asia-Pacific Region

Rachel R. Huxley, et al,  for the Asia Pacific Cohort Studies Collaboration and the Obesity in Asia Collaboration

Circulation. 2011 DOI: 10.1161/CIRCULATIONAHA.111.028373


Previous studies have suggested that there is a novel dyslipidemic profile consisting of isolated low high-density lipoprotein cholesterol (HDL-C) level that is associated with increased risk of coronary heart disease, and that this trait may be especially prevalent in Asian populations.

Methods and Results

Individual participant data from 220 060 participants (87% Asian) in 37 studies from the Asia-Pacific region were included. Low HDL-C (HDL < 1.03 mmol/L in men and < 1.30 mmol/L in women) was seen among 33.1% (95% confidence interval [CI], 32.9 –33.3) of Asians versus 27.0% (95% CI, 26.5–27.5) of non-Asians (P<0.001). The prevalence of low HDL-C in the absence of other lipid abnormalities (isolated low HDL-C) was higher in Asians compared with non-Asians: 22.4% (95% CI, 22.2–22.5) versus 14.5% (95% CI, 14.1–14.9), respectively (P<0.001). During 6.8 years of follow-up, there were 574 coronary heart disease and 739 stroke events. There was an inverse relationship between low HDL-C with coronary heart disease in all individuals (hazard ratio, 1.57; 95% CI, 1.31–1.87). In Asians, isolated low levels of HDL-C were as strongly associated with coronary heart disease risk as low levels of HDL-C combined with other lipid abnormalities (hazard ratio, 1.67 [95% CI, 1.27–2.19] versus 1.63 [95% CI, 1.24 –2.15], respectively). There was no association between low HDL-C and stroke risk in this population (hazard ratio, 0.95 [95% CI, 0.78 to 1.17] with nonisolated low HDL-C and 0.81 [95% CI, 0.67–1.00] with isolated low HDL-C).


Isolated low HDL-C is a novel lipid phenotype that appears to be more prevalent among Asian populations, in whom it is associated with increased coronary risk. Further investigation into this type of dyslipidemia is warranted.


The associations of LDL-C and HDL-C with CHD risk are clear in several populations [1-3]. The importance of HDL-C independent of LDL-C for coronary risk determination is also apparent [4,5]. Isolated low HDL-C in combination with normal TG- and LDL-C levels could be a similar coronary risk as elevated LDL-C [6-8]. These individuals often remain untreated because of their normal LDL-C and total cholesterol levels. This phenotype might especially be common in Asian populations, which is being investigated in this study using data from APCSC (Asia Pacific Cohort Studies Collaboration (APCSC) and OAC (Obesity in Asia Collaboration). Information was available on 69 145 eligible study participants from 24 studies from the APCSC and 150 915 from 13 studies in the OAC. Overall, 87% of men and 86% of women were from Asia.
Low HDL-levels were associated with:
  • ↑ BMI
  • ↑ waist circumference
  • ↑ DM
In adjusted analyses, nonisolated low levels of HDL-C were associated with an almost 60% higher risk of CHD compared with normal levels of HDL-C (HR, 1.57; 95% CI, 1.31-1.87). This association was observed in all individuals, independent of sex, region, and smoking status.

There was no association between low HDL-C and stroke risk in this population.


Isolated low HDL-C level is a common phenotype in Asian populations, associated with an increased risk of CHD. Individuals with this lipid abnormality are unlikely to receive lipid-lowering medications because their TG levels and LDL-C meeting guideline targets. In these regions, HDL-C increasing strategies might potentially be beneficial, such as smoking cessation, weight loss, physical activity, and the use of niacin / fibrates.

Newly developed CETP inhibitors may become very important for CV prevention in this region!


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