Prognostic Usefulness of Free Fatty Acids in Patients With Stable Coronary Heart Disease

      Circulating nonesterified or free fatty acids (FFAs) may contribute to the development of cardiovascular pathology and correlate with ischemia in acute cardiovascular conditions. The aim of this study was to assess whether serum levels of FFAs are associated with long-term prognosis in subjects with stable coronary heart disease. This observational prospective cohort study included 1,206 participants in 3-weeks inpatient rehabilitation programs after acute myocardial infarction, coronary syndromes, or coronary intervention at 2 rehabilitation clinics in Germany (1999 to 2000). Eight-year prognosis (time to a secondary fatal or nonfatal cardiovascular disease event including myocardial infarction and stroke [n = 153] and time to death from any cause [n = 124]) was examined according to FFA quartiles and in spline regression. FFAs were correlated with established serum markers of cardiovascular risk and strongly related to secondary cardiovascular events and all-cause mortality in age- and gender-adjusted analysis. When additionally controlling for multiple established risk factors and risk markers, the hazard ratio in the fourth versus first quartile was 1.34 (95% confidence interval 0.79 to 2.24) for secondary cardiovascular events and 1.09 (95% confidence interval 0.62 to 1.91) for all-cause mortality. Dose-response modeling suggested that very high FFAs might predict an increased risk for mortality (hazard ratio 1.98, 95% confidence interval 0.98 to 4.02, for 95th percentile vs first quartile). In conclusion, FFAs are closely correlated with cardiovascular risk markers, and in particular, very high FFA might identify patients with stable coronary heart disease with worse prognoses.
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        • Pilz S.
        • Marz W.
        Free fatty acids as a cardiovascular risk factor.
        Clin Chem Lab Med. 2008; 46: 429-434
        • Boden G.
        Interaction between free fatty acids and glucose metabolism.
        Curr Opin Clin Nutr Metab Care. 2002; 5: 545-549
        • Pilz S.
        • Scharnagl H.
        • Tiran B.
        • Wellnitz B.
        • Seelhorst U.
        • Boehm B.O.
        • Marz W.
        Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography.
        Eur Heart J. 2007; 28: 2763-2769
        • Arii K.
        • Suehiro T.
        • Yamamoto M.
        • Ito H.
        • Hashimoto K.
        Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid.
        Metabolism. 1997; 46: 1166-1170
        • Mathew M.
        • Tay E.
        • Cusi K.
        Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.
        Cardiovasc Diabetol. 2010; 9: 9
        • Steinberg H.O.
        • Tarshoby M.
        • Monestel R.
        • Hook G.
        • Cronin J.
        • Johnson A.
        • Bayazeed B.
        • Baron A.D.
        Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.
        J Clin Invest. 1997; 100: 1230-1239
        • Carlsson M.
        • Wessman Y.
        • Almgren P.
        • Groop L.
        High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1588-1594
        • Breitling L.P.
        • Grandi N.C.
        • Hahmann H.
        • Wusten B.
        • Rothenbacher D.
        • Brenner H.
        Gamma-glutamyltransferase and prognosis in patients with stable coronary heart disease followed over 8 years.
        Atherosclerosis. 2010; 210: 649-655
        • Rothenbacher D.
        • Koenig W.
        • Brenner H.
        Comparison of N-terminal pro-B-natriuretic peptide, C-reactive protein, and creatinine clearance for prognosis in patients with known coronary heart disease.
        Arch Intern Med. 2006; 166: 2455-2460
        • Apple F.S.
        • Wu A.H.
        • Mair J.
        • Ravkilde J.
        • Panteghini M.
        • Tate J.
        • Pagani F.
        • Christenson R.H.
        • Mockel M.
        • Danne O.
        • Jaffe A.S.
        Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.
        Clin Chem. 2005; 51: 810-824
        • Kleinfeld A.M.
        • Prothro D.
        • Brown D.L.
        • Davis R.C.
        • Richieri G.V.
        • DeMaria A.
        Increases in serum unbound free fatty acid levels following coronary angioplasty.
        Am J Cardiol. 1996; 78: 1350-1354
        • Roos M.
        • von Eynatten M.
        • Heemann U.
        • Rothenbacher D.
        • Brenner H.
        • Breitling L.P.
        Serum fetuin-A, cardiovascular risk factors, and six-year follow-up outcome in patients with coronary heart disease.
        Am J Cardiol. 2010; 105: 1666-1672
        • Duwensee K.
        • Breitling L.P.
        • Tancevski I.
        • Rothenbacher D.
        • Demetz E.
        • Patsch J.R.
        • Ritsch A.
        • Eller P.
        • Brenner H.
        Cholesteryl ester transfer protein in patients with coronary heart disease.
        Eur J Clin Invest. 2010; 40: 616-622
        • von Eynatten M.
        • Hamann A.
        • Twardella D.
        • Nawroth P.P.
        • Brenner H.
        • Rothenbacher D.
        Relationship of adiponectin with markers of systemic inflammation, atherogenic dyslipidemia, and heart failure in patients with coronary heart disease.
        Clin Chem. 2006; 52: 853-859
        • Koenig W.
        • Vossen C.Y.
        • Mallat Z.
        • Brenner H.
        • Benessiano J.
        • Rothenbacher D.
        Association between type II secretory phospholipase A2 plasma concentrations and activity and cardiovascular events in patients with coronary heart disease.
        Eur Heart J. 2009; 30: 2742-2748
        • Pilz S.
        • Scharnagl H.
        • Tiran B.
        • Seelhorst U.
        • Wellnitz B.
        • Boehm B.O.
        • Schaefer J.R.
        • Marz W.
        Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.
        J Clin Endocrinol Metab. 2006; 91: 2542-2547
        • Hosmer D.W.
        • Lemeshow S.
        Applied Survival Analysis: Regression Modeling of Time to Event Data.
        John Wiley, New York, New York1999
        • Desquilbet L.
        • Mariotti F.
        Dose-response analyses using restricted cubic spline functions in public health research.
        Stat Med. 2010; 29: 1037-1057
        • Twardella D.
        • Rothenbacher D.
        • Hahmann H.
        • Wusten B.
        • Brenner H.
        The underestimated impact of smoking and smoking cessation on the risk of secondary cardiovascular disease events in patients with stable coronary heart disease: prospective cohort study.
        J Am Coll Cardiol. 2006; 47: 887-889
        • Hellerstein M.K.
        • Benowitz N.L.
        • Neese R.A.
        • Schwartz J.M.
        • Hoh R.
        • Jacob III, P.
        • Hsieh J.
        • Faix D.
        Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers.
        J Clin Invest. 1994; 93: 265-272
        • Richieri G.V.
        • Anel A.
        • Kleinfeld A.M.
        Interactions of long-chain fatty acids and albumin: determination of free fatty acid levels using the fluorescent probe ADIFAB.
        Biochemistry. 1993; 32: 7574-7580
        • Jouven X.
        • Charles M.A.
        • Desnos M.
        • Ducimetiere P.
        Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population.
        Circulation. 2001; 104: 756-761
        • Charles M.A.
        • Fontbonne A.
        • Thibult N.
        • Claude J.R.
        • Warnet J.M.
        • Rosselin G.
        • Ducimetiere P.
        • Eschwege E.
        High plasma nonesterified fatty acids are predictive of cancer mortality but not of coronary heart disease mortality: results from the Paris Prospective Study.
        Am J Epidemiol. 2001; 153: 292-298
        • Forsblom C.M.
        • Sane T.
        • Groop P.H.
        • Totterman K.J.
        • Kallio M.
        • Saloranta C.
        • Laasonen L.
        • Summanen P.
        • Lepantalo M.
        • Laatikainen L.
        • Matikainen E.
        • Teppo A.M.
        • Koskimies S.
        • Groop L.
        Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.
        Diabetologia. 1998; 41: 1253-1262
        • Pirro M.
        • Mauriege P.
        • Tchernof A.
        • Cantin B.
        • Dagenais G.R.
        • Despres J.P.
        • Lamarche B.
        Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study.
        Atherosclerosis. 2002; 160: 377-384
        • Kupper-Nybelen J.
        • Rothenbacher D.
        • Hahmann H.
        • Wusten B.
        • Brenner H.
        Changes of risk factors in patients with coronary heart disease after in-patient rehabilitation [article in German].
        Dtsch Med Wochenschr. 2003; 128: 1525-1530