phytosterols and Heart-Failure

Patients may present with a variety of syndromes related to ischaemic heart disease. These include unstable or stable angina pectoris, acute myocardial infarction, and occasionally cardiac failure without prior anginal pain or infarction. For the purposes of this review, it will generally be assumed that the condition has been stabilised, though one important aspect of the rehabilitation process is the recognition of continuing or recurrent problems such as angina pectoris and cardiac decompensation. This should then be followed by appropriate intervention. The key components of post-hospital management of such patients are: (i) support; (ii) education; (iii) assessment; (iv) intervention (if necessary); (v) therapy; and (vi) lifestyle modification.

Topics: Adrenergic beta-Antagonists; Alcohol Drinking; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Coronary Restenosis; Exercise Therapy; Heart Failure; Humans; Myocardial Ischemia; Patient Compliance; Patient Education as Topic; Phytosterols; Risk Assessment; Smoking Cessation; Social Support; Thrombolytic Therapy; Weight Loss

Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.

Topics: Animals; Arrhythmias, Cardiac; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cytokines; Death, Sudden, Cardiac; Fibrosis; Heart Failure; Hypercholesterolemia; Inflammation; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytosterols

Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM).. We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6μg/mL, lathosterol 1.4μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia.. Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153mg/dL was a best cut-off value for discrimination of the D-subset.. The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM.

Topics: Adult; Aged; Arrhythmias, Cardiac; Biomarkers; Cardiomyopathy, Dilated; Cholesterol; Female; Heart Failure; Heart Rate; Hospitalization; Humans; Lipid Metabolism; Male; Middle Aged; Phytosterols; Prognosis; Ventricular Function, Left