Lipid profiles of patients with manifest coronary versus peripheral atherosclerosis - Is there a difference?

AIM: Peripheral arterial disease (PAD) and coronary artery disease (CAD) are both caused by atherosclerosis. Serum lipids and lipoproteins are predictive of the development of atherosclerosis but it is not clear if they differ in the two manifestations, PAD and CAD. We tested whether a more detailed characterization of the lipid and lipoprotein patterns of PAD and CAD allows a clear differentiation between the two atherosclerotic phenotypes. METHODS: A cohort of 274 statin-naïve patients with either newly diagnosed imaging proven PAD (n = 89) or stable CAD (n = 185) was characterized using nuclear magnetic resonance- and liquid chromatography-tandem mass spectrometry-based advanced lipid and lipoprotein analysis. An independent cohort of 1239 patients with PAD and CAD was used for validation. RESULTS: We found a significant difference in markers of inflammation as well as ceramide and phosphatidylcholine levels between patients with PAD and CAD. In contrast, basic lipid markers including total cholesterol, LDL cholesterol, HDL cholesterol, lipoprotein(a) or detailed lipoprotein profiles did not differ significantly between patients with PAD and CAD. Applying ratios and scores derived from ceramides and phosphatidylcholines further improved the discrimination between PAD and CAD. These significant differences were independent of body composition, from the status of smoking or type 2 diabetes mellitus, and also from apolipoprotein C-III and other inflammatory parameters which were different between CAD and PAD. CONCLUSION: The present study clearly suggests that PAD and CAD differ in terms of their ceramide- and phosphatidylcholine-based lipid patterns but not in lipoprotein characteristics.

Adherence to statin therapy favours survival of patients with symptomatic peripheral artery disease.

AIMS: We hypothesized that adherence to statin therapy determines survival in patients with peripheral artery disease (PAD). METHODS AND RESULTS: Single-centre longitudinal observational study with 691 symptomatic PAD patients. Mortality was evaluated over a mean follow-up of 50 ± 26 months. We related statin adherence and low-density lipoprotein cholesterol (LDL-C) target attainment to all-cause mortality. Initially, 73% of our PAD patients were on statins. At follow-up, we observed an increase to 81% (P < 0.0001). Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/day (P < 0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/dL (P < 0.0001). The proportion of patients receiving a high-intensity statin increased over time from 38% to 62% (P < 0.0001). Patients never receiving statins had a significant higher mortality rate (31%) than patients continuously on statins (13%) or having newly received a statin (8%; P < 0.0001). Moreover, patients on intensified statin medication had a low mortality of 9%. Those who terminated statin medication or reduced statin dosage had a higher mortality (34% and 20%, respectively; P < 0.0001). Multivariate analysis showed that adherence to or an increase of the statin dosage (both P = 0.001), as well as a newly prescribed statin therapy (P = 0.004) independently predicted reduced mortality. CONCLUSION: Our data suggest that adherence to statin therapy is associated with reduced mortality in symptomatic PAD patients. A strategy of intensive and sustained statin therapy is recommended.

Development of a 3-Dimensional Prognostic Score for Patients With Symptomatic Peripheral Artery Disease: PAD3D Score.

Peripheral artery disease (PAD) is a high-risk condition for cardiovascular (CV) events, but no specific prognosis assessment tool exists. We developed an individual risk score (PAD3D) based on the combined predictive value for mortality, including (1) age, (2) severity of PAD, and (3) extent of atherosclerosis. Patients (n = 1310) with symptomatic PAD were followed up for a mean of 50 ± 26 months. The cohort was randomly subdivided into a test and validation cohort. All-cause and CV mortality were prospectively analyzed for PAD3D score and in combination with classical risk factors. For the test and validation cohort (n = 655 each), all-cause and CV mortality were predicted (P < .001) by the PAD3D score. Additional inclusion of classical risk factors did not increase discrimination compared with PAD3D as "area under receiver-operating characteristic" curves were similar for both scores at any time point. Thus, the addition of the classical risk factors to PAD3D did not further improve the prognostic value. The PAD3D score provides a risk gradient of a 4.5-fold increase in all-cause and CV mortality. We developed a score for precise prediction of all-cause and CV mortality. The PAD3D score promises to allow for personalized goals in risk intervention.