Plasma levels of high-density lipoprotein cholesterol and outcomes in pulmonary arterial hypertension.
BACKGROUND
High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease.


OBJECTIVE
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.


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.
Heresi
Gustavo A
GA
Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Aytekin
Metin
M
Newman
Jennie
J
DiDonato
Joseph
J
Dweik
Raed A
RA
D008076:Cholesterol, HDL / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000473:pathology; D007333:Insulin Resistance; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012189:Retrospective Studies; D016896:Treatment Outcome
D008076:Cholesterol, HDL
Am J Med. 1977 May;62(5):707-14
193398
Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L432-8
19561137
Eur Respir J. 2009 Feb;33(2):318-24
19047320
Diabetes Care. 2005 Feb;28(2):385-90
15677797
Am Heart J. 2009 Mar;157(3):548-55
19249427
N Engl J Med. 2007 Sep 27;357(13):1301-10
17898099
Eur Respir J. 2008 Aug;32(2):503-12
18669790
Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1383-91
19542023
Blood. 2009 Jan 29;113(5):1122-8
19023114
Circulation. 2004 Jul 27;110(4):380-5
15262834
Diabetes Care. 2000 Jan;23(1):57-63
10857969
Circulation. 1990 Jun;81(6):1784-91
2111741
Lancet. 2008 Jun 7;371(9628):1927-35
18501419
Arch Intern Med. 2008 May 12;168(9):969-78
18474761
J Am Coll Cardiol. 2007 Jan 30;49(4):403-14
17258085
N Engl J Med. 2004 Sep 30;351(14):1425-36
15459304
J Am Coll Cardiol. 2009 Apr 7;53(14):1211-8
19341863
Circulation. 2002 Mar 26;105(12):1424-8
11914249
J Am Coll Cardiol. 2009 Jun 2;53(22):2061-7
19477356
Circulation. 2009 Oct 20;120(16):1640-5
19805654
Rheumatol Int. 2005 Jun;25(5):379-83
15700114
Diabetes Care. 2004 Nov;27(11):2676-81
15505004
Circulation. 2007 Mar 13;115(10):1275-84
17339547
J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S43-S54
19555858
Chest. 2009 Jul;136(1):31-36
19188551
Diabetes Care. 2002 Jul;25(7):1177-84
12087016
Am J Respir Crit Care Med. 2010 Sep 1;182(5):661-8
20448092
Thromb Res. 1997 Oct 1;88(1):41-9
9336872
Arterioscler Thromb. 1994 Nov;14(11):1775-83
7947603
Eur J Cardiovasc Prev Rehabil. 2008 Oct;15(5):594-8
18753952
Ann Intern Med. 2003 Nov 18;139(10):802-9
14623617
Diabetes Care. 2003 May;26(5):1513-7
12716814
Atherosclerosis. 1999 Nov 1;147(1):133-8
10525134
Circulation. 1994 Jun;89(6):2525-32
8205660
J Clin Invest. 1999 Jan;103(2):219-27
9916134
Diabetologia. 1985 Jul;28(7):412-9
3899825
Am J Cardiol. 1991 Dec 1;68(15):1425-30
1746422
J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S78-S84
19555861
Diabetes. 2003 May;52(5):1210-4
12716754
Circulation. 2003 Dec 2;108(22):2751-6
14638544
J Clin Invest. 1988 Sep;82(3):803-7
3047170