Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear. AIM: To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events. METHODS: From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events). RESULTS: The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE. CONCLUSION: Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction.

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI). Methods: We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level. Results: One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan-Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06-3.45, p = 0.03) on events than other known atherosclerosis risk factors. Conclusions: The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words).

Response to pre-dilatation with POBA can predict target lesion revascularization after DCB angioplasty for de novo small coronary artery lesions.

OBJECTIVE: To assess the determinants of target lesion revascularization (TLR) after drug-coated balloon (DCB) angioplasty for de novo small coronary artery lesions. METHODS: This retrospective study enrolled consecutive lesions from patients that were in a stable condition and had undergone successful DCB treatment for de novo small coronary artery lesions. The study endpoint was TLR and major adverse cardiac events at 12 months. RESULTS: A total of 68 patients with 83 lesions were enrolled in the study. Of these, 11 (13.3%) lesions required TLR. Mean ± SD pre-dilatation balloon diameters were similar in the non-TLR (2.33 ± 0.72 mm) and TLR (2.18 ± 0.36 mm) groups. A comparison of the two groups showed that post/pre-lumen area ratio during pre-dilatation (%) by plain old balloon angioplasty (POBA) was significantly and negatively associated with TLR and the optimal cut-off point was 170%. Cox proportional hazard and multivariate regression analyses showed that post/pre-lumen area ratio was the only independent predictor of TLR (hazard ratio 0.9318; 95% confidence interval 0.9001, 0.9645). CONCLUSION: Greater pre-dilatation using POBA, assessed as the post/pre-lumen area ratio, may be independently associated with a lower 12-month TLR rate in patients undergoing DCB angioplasty for de novo small coronary lesions.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral artery disease (PAD).

BACKGROUND AND AIMS: Despite advances in the treatment of peripheral artery disease (PAD), cardiovascular events and death rates remain high. This study aimed at identifying markers of outcome in patients with PAD undergoing endovascular therapy (EVT). METHODS: Consecutive patients undergoing EVT were recruited. Markers of oxidative stress (malondialdehyde-modified low-density lipoprotein [MDA-LDL]), inflammation (IL-6; high-sensitivity C-reactive protein [hsCRP]) and fibrinolysis (D-dimer) were measured pre-EVT and at post-EVT time-points to 36 h. Clinical follow-up assessed major cardiovascular and/or limb events. RESULTS: In the 35 patients enrolled, mean MDA-LDL levels decreased from a baseline level of 106.2 U/L to 72.6 U/L immediately post-EVT (p<0.0001); levels remained significantly reduced at all time-points. IL-6, hsCRP and D-dimer increased and were significantly higher at the 36 h time-point. A significant, negative association was seen between decreased MDA-LDL and pre-EVT hsCRP levels (r = -0.42, p=0.012). Clinical follow-up data were obtained for a mean period of 16 months. MDA-LDL ratios (obtained by comparison of post- and pre-EVT values) allowed assessment of high (≥0.495) and low (<0.495) ratio groups. A significantly higher rate of major adverse events, including limb-related events or death, was seen in the low ratio group (p<0.001). Cox proportional hazard analysis including traditional risk factors indicated that this ratio is a significant predictor of clinical endpoints (HR = 0.4210, p=0.0154). An association with clinical outcome was not observed with the other candidate biomarkers. CONCLUSIONS: Assessment of pre- and post-EVT MDA-LDL levels is a promising marker of clinical outcome in patients with PAD.