Comorbidity in lipoprotein apheresis: Their role in the era of new lipid-lowering therapies.

BACKGROUND: Despite advance in pharmacotherapy of lipid disorders, lipoprotein apheresis (LA) plays a leading role in the management of severe hypercholesterolemia and in atherosclerosis prevention. METHODS: Aim of this study was to retrospectively evaluate Charlson Comorbidity Index (CCI), presence of major comorbidity, and/or concomitant polypharmacy (definite as 5+ drugs daily) in patients with inherited dyslipidemias on chronic LA. RESULTS: Since 1994, we performed more than 500 LA treatment/year and followed a total of 83 patients (age 56 [47-65] years, male 75%). In subjects with more than 5 years of LA treatment (38 patients, age 54 [45-62] years, male 66%), at the end of the observation time (9 [7-16] years), patients had higher CCI, polypharmacy, anemia, heart failure, peptic ulcer disease, and benign prostatic hyperplasia. DISCUSSION: Even in the era of new lipid-lowering therapies, the LA treatment established itself as a safe and lifesaving intervention. Patients on chronic LA require a multidisciplinary approach to address their comorbidity and the apheresis unit's medical staff (doctors and nurses) play a pivotal role creating a bridge toward the general practitioner and other specialists for overcoming clinical issues.

LDL apheresis improves coronary flow reserve on the left anterior descending artery in patients with familial hypercholesterolemia and chronic ischemic heart disease.

BACKGROUND: LDL apheresis (LA) influences the microcirculation, endothelial function and cardiovascular homeostasis. The aim of our study was to analyze temporal variations of coronary flow reserve (CFR) on the left anterior descending artery, obtained during dipyridamole stress echocardiography (DSE), in patients with severe familial hypercholesterolemia on LA (LA group) or not (not LA group) and ischemic heart disease (IHD). METHODS: The LA group consisted in 10 patients (mean age 65 ± 7 years, male 70%) with Familial Hypercholesterolemia and chronic IHD on maximally tolerated lipid lowering therapy and chronic LA treatment (median 7 years, interquartile range 6-14 years). Hyperlipoproteinemia (a) was also present in 6/10 subjects. LA was performed biweekly by dextran-sulfate or heparin-induced LDL precipitation technique. IHD was diagnosed at a mean age of 44 ± 8 years. The control group was matched for age, sex and follow-up period. CFR was calculated as the ratio between blood diastolic velocity sampled at peak stress with dipyridamole and baseline diastolic velocity (normal value > 2.0). No relevant comorbidities were present. RESULTS: During a median follow-up of 27 months (interquartile range 23-50 months), a significant increase in CFR (from 1.86 ± 0.47 to 2.25 ± 0.35; p < 0.001) was observed in LA group. During this period, no patients modified their anti-ischemic therapy and no cardiovascular events were reported. In the control group, during the study time (24 months - interquartile range 14-57 months) no significant variation in CFR was observed (from 2.08 ± 0.39 to 1.92 ± 0.26; p 0.283). CONCLUSION: Myocardial blood perfusion, measured as CFR by dipyridamole stress echocardiography-is increased in patients with severe familial hypercholesterolemia chronically treated with LA. DSE might be a reliable tool to monitor the therapeutic effect of lipid lowering therapy.

Statin intolerance in heterozygous familial hypercolesterolemia with cardiovascular disease: After PCSK-9 antibodies what else?

Background Familial hypercholesterolemia is the elective clinical condition that deserves the maximal personalisation in lipid-lowering therapy, especially in the presence of statin intolerance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a promising approach to lower low-density lipoprotein (LDL) cholesterol. Methods We enrolled 18 patients (mean age 62 ± 8 years, 72% men) affected by heterozygous familial hypercholesterolemia and cardiovascular disease, with a history of statin intolerance assigned to PCSK9 inhibitors. Six patients were also on LDL apheresis. Associated Lp(a)-hyperlipoproteinemia (defined as >60 mg/dl) was observed in two out of 18 subjects. PCSK9 inhibitor injectable monoclonal antibodies were administered, every 2 weeks, on top of patient therapy for 12 ± 4 weeks (evolocumab in 15 subjects, alirocumab in three subjects). Results After 3 months (12 ± 4 weeks) of therapy, a decrease in total cholesterol (-35%), LDL cholesterol (-51%) and Lp(a) levels (-20%) was observed. Five out of 18 patients reached LDL cholesterol levels of <70 mg/dl, seven showed LDL cholesterol values between 71 and 100 mg/dl, and six out of 18 still had LDL cholesterol levels above 100 mg/dl. Among the six patients with LDL cholesterol levels >100 mg/dl, three were already on LDL apheresis before the PCSK9 inhibitor treatment, while three were referred to LDL apheresis treatment. Adverse events were reported in two out of 18 patients on evolocumab: one presented with flu-like syndrome and the other reported episodes of mild difficulty in maintaining concentration. Conclusions PCSK9 inhibitors represent a novel therapeutic tool for patients with familial hypercholesterolemia who are intolerant to statins. However, more data are needed before cleaning up the old therapeutic armamentarium, such as LDL apheresis, which is likely to preserve its valuable role also in the new lipid-lowering era.

Cognitive impairment and polidistrectual atherosclerotic disease in chylomicronemia syndrome: a case report.

A case of chylomicronemia syndrome is reported in a 72-year-old male with distinctive features of chronic pancreatic damage, severe hypertriglyceridemia, polidistrectual atherosclerosis and premature cognitive impairment. Although the patient had a positive history for recurrent episodes of pancreatitis the characteristic lesions of the hyperchylomicronemia syndrome, such as eruptive xanthomas and lipemia retinalis, were not present and splenomegaly could not be documented due to a previous post-traumatic splenectomy. Based on clinical phenotype, an apolipoprotein C-II deficiency was excluded by a fresh plasma infusion test, in which clarification of the patient plasma was not obtained. The absence of changes in the lipoprotein electrophoretic plasma after heparin infusion can be secondary to a lipoprotein lipase deficiency, a rare genetic disorder with an incidence of one per million. In relation to the resistance to diet and drugs, plasma exchange therapy was performed. After 3 years of this treatment there was no significant progression of atherosclerosis.