Plasma levels of high-density lipoprotein cholesterol and outcomes in pulmonary arterial hypertension

Am J Respir Crit Care Med. 2010 Sep 1;182(5):661-8. doi: 10.1164/rccm.201001-0007OC. Epub 2010 May 6.


Rationale: High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease.

Objectives: We hypothesized that HDL-C is associated with clinical outcomes in pulmonary arterial hypertension (PAH).

Methods: Plasma HDL-C concentrations were measured in 69 patients with PAH (age, 46.7 +/- 12.9 yr; female, 90%) and 229 control subjects (age, 57 +/- 13 yr; female, 48%). Clinical outcomes of interest included hospitalization for PAH, lung transplantation, and all-cause mortality. Survival and time to clinical worsening curves were derived by the Kaplan-Meier method. Cox regression modeling of outcome versus HDL-C with individual covariate adjustments was performed.

Measurement and main results: HDL-C was low in subjects with PAH compared with control subjects (median, interquartile range: PAH: 36, 29-40 mg/dl; control subjects: 49, 40-60 mg/dl; P < 0.001). An HDL-C level of 35 mg/dl discriminated survivors from nonsurvivors, with a sensitivity of 100% and specificity of 60%. After a median follow-up of 592 days, high HDL-C was associated with decreased mortality (hazard ratio for every 5-mg/dl increase in HDL-C, 0.643; 95% confidence interval, 0.504-0.822; P = 0.001) and less clinical worsening (hazard ratio for every 5-mg/dl increase in HDL-C, 0.798; 95% confidence interval, 0.663-0.960; P = 0.02). HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P < 0.05).

Conclusions: Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH. This association does not appear to be explained by underlying cardiovascular risk factors, insulin resistance, or the severity of PAH.

MeSH terms

  • Cholesterol, HDL / blood*
  • Disease Progression
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / pathology
  • Insulin Resistance
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Retrospective Studies
  • Treatment Outcome


  • Cholesterol, HDL