The predictive role of atherogenic dyslipidemia in subjects with non-coronary atherosclerosis Kaspar Berneis a, 1 , Manfredi Rizzo b, ⁎ , 1 , Giatgen A. Spinas a , Gabriele Di Lorenzo b , Gaetana Di Fede b , Ilenia Pepe b , Vincenzo Pernice c , Giovam Battista Rini b a Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Zurich, Switzerland b Department of Internal Medicine and Emerging Diseases, University of Palermo, Italy c Angiographic Unit, Villa Maria Eleonora Hospital, Palermo, Italy abstract article info Article history: Received 9 April 2009 Received in revised form 6 May 2009 Accepted 6 May 2009 Available online 9 May 2009 Keywords: Atherosclerosis HDL-cholesterol Triglycerides Small dense LDL Atherogenic lipoprotein phenotype Background: Recent findings have suggested that subjects with non-coronary atherosclerosis may show elevated prevalence of atherogenic dyslipidemia, including higher triglyceride levels, reduced HDL- cholesterol concentrations and increased levels of small, dense low-density lipoproteins (LDL). These three lipid abnormalities constitute the so-called “atherogenic-lipoprotein-phenotype” (ALP) but its predictive role in these patients still remains to be established. Methods: We performed a 2-year follow-up study to assess clinical and biochemical predictors of cardiovascular events in 44 male patients (64 ± 5 years, BMI: 27 ± 3), 26 with peripheral arterial disease and 18 with abdominal aortic aneurysm. Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Results: Clinical events were registered in the 43% of patients. At univariate analysis we found that patients with events had increased prevalence of hypertension (p = .0098), diabetes (p = .0089), family history of cardiovascular diseases (p = .0089), of elevated small, dense LDL (p = .0222) and ALP (p = .0224). At multivariate analysis (including all clinical and laboratory variables) we found the following independent predictors of events: hypertension (OR 8.9, p =.0347), diabetes (OR 9.4, p = .0270), elevated small, dense LDL (OR 6.9, p =.0488) and ALP (OR 8.7, p = .0497). Conclusions: This is the first study that evaluated the predictive role of ALP beyond traditional cardiovascular risk factors in patients with peripheral arterial disease or abdominal aortic aneurysm. We confirmed that hypertension and diabetes are strong predictors of cardiovascular events in these subjects but ALP seems to be an independent predictor too. Yet, the therapeutical consequences of these findings need to be tested by future studies. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Clinical forms of non-coronary atherosclerosis carry a risk for coronary heart disease equal to those with established coronary heart disease; these conditions include peripheral arterial disease (PAD), carotid artery disease and abdominal aortic aneurysm (AAA) [1]. Therefore assessment and treatment of risk factors in such patients are of great relevance. There is general agreement that diabetes, smoking and hypertension represent the most important risk factor for PAD and AAA; other risk factors include male gender, older age and dyslipidemia [2]. Yet, the association between PAD and AAA with plasma lipids and lipoproteins has not been as extensively investigated as for coronary artery disease and results have been less conclusive. Common findings in these conditions include elevated plasma total-cholesterol, low- density-lipoproteins (LDL)-cholesterol and triglyceride levels as well as reduced plasma high-density-lipoproteins (HDL)-cholesterol concen- trations [2], but contrasting results have been shown too [3,4]. We have also recently shown that, beyond traditional plasma lipids, patients with non-coronary forms of atherosclerosis have increased levels of atherogenic small, dense LDL [5–7]. Indeed, a number of evidences suggest that both the quality and the quantity of LDL exert a direct influence on the cardiovascular risk [8,9]. LDL size has been established as an important predictor of cardiovascular events and progression of coronary heart disease [10] and the predominance of small, dense LDL has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III [1]. In addition, in recent years it has become evident that the atherogenic lipoprotein phenotype (ALP), characterised by decreased HDL-cholesterol, mod- erately raised triglycerides and increased levels of small, dense LDL, is Clinica Chimica Acta 406 (2009) 36–40 ⁎ Corresponding author. Department of Clinical Medicine and Emerging Diseases, University of Palermo, Via del Vespro, 141, 90127 Palermo, Italy. Tel./fax: +39 091 6552945. E-mail address: mrizzo@unipa.it (M. Rizzo). 1 These two authors contributed to the present study equally. 0009-8981/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2009.05.002 Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim