atrial-natriuretic-factor and Hyperlipoproteinemia-Type-II

Topics: Amino Acid Sequence; Angiotensinogen; Apoproteins; Arteriosclerosis; Atrial Natriuretic Factor; Cloning, Molecular; DNA; Genetic Engineering; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type III; Hypertension; Myosins; Receptors, Cell Surface; Receptors, Lipoprotein; Sodium-Potassium-Exchanging ATPase

Lipid-apheresis (LA) is thought to improve microcirculation. However, limited data are available on the effects on peripheral microcirculation. We investigated upper limb microcirculation of 22 patients undergoing regular LA on a weekly basis before and after LA. Using standardized semiquantitative scales, we analyzed blood flow, vasomotor function, and erythrocyte aggregation by capillary microscopy. In addition, capillary blood flow in quiescence and under heat and cryo-stress was evaluated by photoplethysmographic and laser Doppler anemometry. Moreover, levels of vasoactive mediators adrenalin, noradrenalin, endothelin-1 (ET-1), atrial natriuretic peptide (ANP), asymmetrical dimethyl-arginine (ADMA), as well as total protein and fibrinogen were measured. We found a significant increase in blood flow, the number of perfused capillaries and an improvement of erythrocyte aggregation by capillary microscopy. Using laser Doppler anemometry, we were able to show that this increase was predominantly located in the superficial layer capillaries (Δ44.53 ± 135.81%, n.s.) and less so in deeper layer arterioles (Δ2.75 ± 24.84%, n.s.). Vascular response to heat and cryo stress was also improved after LA but failed to reach significance. LA significantly reduced levels of epinephrin (-33 ± 39.2%), ANP (-28.8 ± 20.2%), ADMA (-74.1 ± 23%), and fibrinogen (-45.4 ± 19.7%) when comparing before LA and after LA values. In summary, we found an improvement in the microcirculation of the upper limbs under LA, which may result from a decrease of vasoconstrictors, improvement of vasomotor function, and a decrease in blood viscosity or erythrocyte aggregation.

Topics: Adult; Aged; Arginine; Atrial Natriuretic Factor; Blood Component Removal; Blood Flow Velocity; Endothelin-1; Epinephrine; Erythrocyte Aggregation; Female; Fibrinogen; Hand; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Laser-Doppler Flowmetry; Lipids; Male; Microcirculation; Microscopic Angioscopy; Middle Aged; Norepinephrine; Photoplethysmography

Atrial natriuretic peptide (ANP or NPPA) is the precursor protein of the form of amyloidosis called isolated atrial amyloid (IAA), which is related to the increased incidence of cardiac pathological conditions with age. Familial hypercholesterolemia (FH) patients are characterized by high concentrations of low-density lipoprotein cholesterol (LDL-C), which frequently gives rise to premature coronary artery disease (CAD). However, not all FH patients have the same clinical phenotype. The aim of the present study was to assess the relationship between ANP polymorphisms and apolipoprotein (Apo) A1 levels and CAD risk in FH patients. Transition T2238C, which leads to ANP with two additional arginines, and G664A (Val7Met) were investigated with lipid values and clinical phenotype in 83 FH patients. ApoA1 and HDL cholesterol levels were lower in GA patients compared to GG homozygotes for the G664A polymorphism. No association was found between the G664A polymorphism and CAD in our population. Moreover, ApoA1 and high-density lipoprotein cholesterol (HDL-C) levels did not differ among the different genotypes of the T2238C polymorphism, even after adjusting for age and sex. The 664A allele of the ANP polymorphism is associated with lower levels of ApoA1 and HDL-C in FH patients, but not with CAD risk. Concerning the T2238C polymorphism, no effect was found on lipid parameters or CAD incidence.

Topics: Adult; Atrial Natriuretic Factor; Comorbidity; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Greece; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Polymorphism, Single Nucleotide; Risk Factors; Valine

Fifty-seven patients with familial hypercholesterolemia (FH) with mean age of 48 years (range 30 to 69), participated in a follow-up examination 5.5 years after the completion of a 1-year trial with lovastatin, cholestyramine, probucol, or omega-3 fatty acids. The goals were to record quality of life, compliance to treatment, adverse effects, and clinical outcome. The quality of life was similar to that in a Norwegian reference population. The factors causing most distress to patients were keeping a diet low in saturated fats, taking medication, and fear of death. The medication was mostly prescribed in maximum dosages. At follow-up, the reduction in total cholesterol was 36% (p < 0.05), low-density lipoprotein (LDL) cholesterol 38% (p < 0.05), triglycerides 20% (p < 0.05) compared with being on diet therapy only. High-density lipoprotein (HDL) cholesterol increased 8% (p < 0.05). Intake of saturated and monounsaturated fat increased 1.5% and 1.7% (p < 0.05), respectively; polyunsaturated fat was unchanged. Three patients experienced myocardial infarction, of whom 2 died and 1 developed angina pectoris. Before the start of lovastatin treatment, 27 coronary events occurred per 1,000 patient-years in this group compared with 12 events per 1,000 patient-years thereafter. Of 28 patients reporting adverse events, 4 discontinued lovastatin and 3 discontinued cholestyramine. Several practical and psychological difficulties were associated with FH. Long-term intensive lipid-lowering therapy was possible in FH outpatients without loss of effect and with good compliance to therapy. Intensive therapy, today is, however, not sufficient for many FH patients to reach a therapeutic goal of LDL cholesterol < 4.0 mmol/L. More potent lipid-lowering agents are needed.

Topics: Adult; Aged; Anticholesteremic Agents; Atrial Natriuretic Factor; Cholesterol; Cholestyramine Resin; Female; Humans; Hyperlipoproteinemia Type II; Lovastatin; Male; Middle Aged; Probucol; Quality of Life; Treatment Outcome