Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis

Abstract

Background: Primary biliary cirrhosis (PBC), a chronic cholestatic liver disease, is frequently associated with severe hypercholesterolaemia but the clinical significance of this finding is unclear. Aims: To characterise changes in serum lipid profile over time and to assess the risk of cardiovascular disease in PBC. Subjects and methods: We studied a cohort of 400 PBC patients for 6.2 years (range 4 months to 24 years) by serial determinations of serum lipid levels and registration of all cardiovascular events. Subjects included in an Italian prospective population based study served as controls. Results: At presentation, 76% of patients had serum cholesterol levels >5.2 mmol/l. Hyperbilirubinaemic patients had higher total cholesterol and lower high density lipoprotein (HDL) cholesterol levels (p<0.001). With time, disease progression was associated with a reduction in total (p<0.001) and HDL (p<0.05) cholesterol. The incidence of cardiovascular events was similar to that of the general population (cerebrovascular events: standardised ratio 1.4; 95% confidence interval 0.5-3.7; coronary events: 2.2; 0.9-4.3). Hypertension was associated with an increased risk of cardiovascular events (3.8; 1.6-8.9). Association with moderate hypercholesterolaemia was of borderline significance (3.8; 0.9-17) whereas severe hypercholesterolaemia was not associated with increased risk (2.4, 0.5-11). Conclusions: In PBC, serum cholesterol levels markedly increase with worsening of cholestasis, and decrease in the late disease stages, despite a severe reduction in biliary secretion. Marked hypercholesterolaemia, typical of severe longstanding cholestasis, is not associated with an excess risk of cardiovascular disease while less advanced patients with moderate hypercholesterolaemia are exposed to an increased cardiovascular risk. Putative protective factors in PBC patients with severe hypercholesterolaemia should be assessed.

Risk factors and comorbidities in primary biliary cirrhosis: A controlled interview-based study of 1032 patients

“…24 Among non-autoimmune conditions, we found a high prevalence of hypercholesterolemia among PBC cases, consistent with chronic cholestasis and induction of lipoprotein X synthesis and similar to previous reports. 25 We also report for the first time a higher prevalence of hay fever among controls compared to patients (18% vs. 14%; P ϭ .0113). Our data did not reveal an association between PBC and breast cancer, the prevalence of which was not significantly different between cases and controls.…”

“…The model for sociodemographic and clinical candidate variables included sex, education level, body mass index (BMI) at age 25 (grouped as "high" [Ͼ30], "medium" [25][26][27][28][29][30], and "low" [Ͼ25]), indicators for whether the person had at least one vaccination (for chickenpox, hepatitis A, hepatitis B, diphteria-pertussis-tetanus, rubella, mumps, polio, small pox, or tuberculosis) and whether the person had had at least one urogenital condition (including pelvic or vaginal infection in women or any urinary tract infection in both sexes). Additionally, the following were considered to be possible explanatory variables: at least one first-degree family member (parent, sibling, or offspring) having PBC, systemic lupus erythematosus (SLE), arthritis, multiple sclerosis, Raynaud syndrome, Sjögren syndrome, scleroderma, polymyositis, autoimmune thyroid disease, or diabetes mellitus.…”

Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid

“…Hypercholesterolemia may constitute a major risk factor for cardiovascular disease in PBC. 50 Early and intermediate stages of PBC have mildly elevated very LDL-C and LDL-C and markedly increased HDL-C and are associated with an increased cardiovascular risk, while advanced PBC exhibits markedly elevated LDL-C and decreased HDL-C. 8,12,13 Hypercholesterolemia seems to be associated with increased carotid artery intima media thickness and carotid stenosis in hypertensive or older PBC patients who will benefit from lipid-lowering medication. 10 We therefore examined the lipoprotein pattern under statin therapy in our patients.…”

“…[10][11][12][13][14][15] 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as statins, are well established in the management of dyslipidemia. Their potential to reduce the concentration of low-density lipoprotein cholesterol (LDL-C) results in decreased cardiovascular morbidity and mortality.…”

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

“…Hyperlipidemia with abnormal total cholesterol (TC) levels and elevated LDL and HDL-cholesterol is reported in most of the patients with cholestatic liver disorders, particularly PBC. Reduction of TC and LDL-cholesterol is seen with disease progression and treatment with UDCA (68,204) . Hyperlipidemia in cholestasis is due to accumulation of lipoprotein X.…”