Relation of red blood cell distribution width to risk of major adverse cardiovascular events, death, and effect of alirocumab after acute coronary syndromes.

Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW. Associations of baseline RDW with risk of MACE and death were analyzed in the placebo group in adjusted proportional hazards models. Interactions of RDW and treatment on the risk of MACE and death were evaluated. An increasing quartile of RDW was associated with characteristics that predicted risk of MACE and death including age, hypertension, diabetes, atherosclerotic conditions and events, revascularizations, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. After adjusting for baseline characteristics associated with the risk of MACE or death, baseline RDW remained independently associated with the risk of MACE and death in the placebo group (hazard ratios [95% confidence intervals] 1.08 [1.02-1.15] and 1.13 [1.03-1.24] per 1% increase of RDW, respectively, both p <0.001). There was no interaction of RDW and treatment on MACE or death, nor did alirocumab affect RDW. RDW was associated with an increased risk of MACE and death, independent of established risk factors.

Effect of Lipoprotein Apheresis on Progression of Carotid Intima-Media Thickness in Patients with Severe Hypercholesterolemia.

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)>60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis.

PURPOSE OF REVIEW: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. RECENT FINDINGS: The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.

Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD). In the United States, lipoprotein apheresis (LA) therapy is approved for patients with familial hypercholesterolemia. Germany uses LA therapy for patients with an Lp(a) > 60 mg/dL, normal low-density lipoprotein cholesterol (LDL-C) levels, and CVD. LA therapy in this population demonstrated a >70% reduction in CVD events. In the United States, LA is only approved for patients with elevated LDL-C levels, regardless of Lp(a) level. OBJECTIVE: The objective of the study was to evaluate clinical significance of Lp(a) reduction with LA therapy in the United States. METHODS: A retrospective cohort study at one LA site in the United States evaluated 14 CVD patients with elevated Lp(a) and near normal LDL-C levels. Patient data was analyzed to demonstrate possible clinical benefit in reducing Lp(a) levels with LA to mitigate risk of major adverse cardiovascular events. RESULTS: Pre-LA patients' mean LDL-C and Lp(a) were 80 mg/dL and 138 mg/dL, respectively. LA therapy demonstrated a reduction of mean LDL-C to 29 mg/dL and Lp(a) to 51 mg/dL. These represent a percent reduction of 64% and 63% for LDL-C and Lp(a), respectively. There was a 94% reduction in major adverse cardiovascular events over a mean treatment period of 48 months. CONCLUSION: The treatment of CVD patients with an elevated Lp(a) and near normal LDL-C with LA in a U.S. treatment center demonstrated a significant reduction in future CVD events. LA should be considered for patients in the United States suffering from an elevated Lp(a) and progressive CVD.