Suboptimal consideration and management of potential familial hypercholesterolaemia in patients with suspected premature coronary artery disease.

INTRODUCTION: Familial hypercholesterolaemia (FH) is caused by an autosomal dominant mutation of the low density lipoprotein (LDL) receptor gene, resulting in high levels of LDL cholesterol and premature coronary artery disease (P-CAD). Studies have shown low detection rates of FH in patients admitted with P-CAD and suboptimal therapy at discharge. METHODS: Males aged ≤ 55 years and females aged ≤ 60 years who were admitted with P-CAD to the Gold Coast Hospital during a 12-month period were included in the study. The demographics, cardiovascular risk factors, examination findings, admission and discharge cardiac medications and provisional diagnoses were recorded. Diagnosis of FH was made according to internationally accepted criteria. RESULTS: 210 patients were included in the study; 60% were male and 40% female (mean age 48 and 50 years, respectively). Only 96 (46%) patients' fasting lipid levels were documented (LDL-C 2.75 ± 1.0 mmol/L), and FH was considered in three (1%) cases. According to the Dutch Lipid Network criteria, three (1%) patients had probable FH, 50 (24%) had possible FH and 60 (29%) had unlikely FH. Of the 53 patients with probable or possible FH, 12 (23%) were discharged without statin therapy and 13 (25%) on the maximum recommended statin dose. CONCLUSION: Our study has found inadequate documentation and screening for FH and suboptimal therapy in patients admitted with P-CAD. We propose a simple screening tool that can be applied to all patients admitted with suspected P-CAD in order to improve the detection rate of FH and its management.

Fenofibrate therapy in carnitine palmitoyl transferase type 2 deficiency.

Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2) deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure.

Statin-associated myopathy.

Myopathy occurs in 0.1%-0.2% of patients receiving statins in clinical trials. This adverse effect is shared by all statins, but is more common with cerivastatin, especially in combination with gemfibrozil. The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions. Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available.

Effects of multiple stenoses and post-stenotic dilatation on non-Newtonian blood flow in small arteries.

Fully-developed one-dimensional Casson flow through a single vessel of varying radius is proposed as a model of low Reynolds number blood flow in small stenosed coronary arteries. A formula for the resistance-to-flow ratio is derived, and results for yield stresses of tau 0 = 0, 0.005 and 0.01 Nm-2, viscosities of mu = 3.45 x 10(-3), 4.00 x 10(-3) and 4.55 x 10(-3) Pa.s and fluxes of 2.73 x 10(-6), x 10(-5) and x 10(-4) m3 s-1 are determined for segment of 0.45 mm radius and 45 mm length, with 15 mm abnormalities at each end where the radius varies by up to +/- 0.225 mm. When tau 0 = 0.005 N m-2, mu = 4 x 10(-3) Pa.s and Q = 1, the numerical values of the resistance-to-flow ratio vary from lambda = 0.525, when the maximum radii of the two abnormal segments are both 0.675 mm, to lambda = 3.06, when the minimum radii are both 0.225 mm. The resistance-to-flow ratio moves closer to unity as yield stress increases or as blood viscosity or flux decreases, and the magnitude of these alterations is greatest for yield stress and least for flux.

A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia.

We directly compared the safety and efficacy of atorvastatin and simvastatin in hypercholesterolemic patients. This 1-year, randomized, double-blind study was performed at 9 community- and university-based research hospitals in Australia. One-hundred seventy-seven patients between the ages of 18 and 80 years with baseline low-density-lipoprotein (LDL) cholesterol > or = 4.14 and < or = 7.76 mmol/L (160 and 300 mg/dl, respectively) and triglycerides < or = 4.52 mmol/L (400 mg/dl) received once-daily dosing with atorvastatin (Lipitor) 10 mg or simvastatin (Zocor) 10 mg. At week 16, the dose of medication was titrated to atorvastatin 20 mg or simvastatin 20 mg if patients did not meet LDL cholesterol target of < or = 3.36 mmol/L (130 mg/dl). Efficacy was reported as percent change from baseline in LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, total triglycerides, high-density lipoprotein cholesterol, apolipoproteins AI and B, and lipoprotein(a). Atorvastatin caused significantly greater reductions from baseline than did simvastatin for LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, triglycerides, and apolipoprotein B (p <0.05). No patient in either treatment group had clinically important elevations in creatine phosphokinase, alanine aminotransaminase, or aspartate aminotransaminase. No serious adverse events were considered associated with treatment. With atorvastatin 10 mg, 46% of the patients achieved LDL cholesterol target goal by week 16, whereas only 27% of the simvastatin patients achieved the target goal at the 10-mg dose. This cholesterol-lowering profile affords utility in many patient types.

A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apo E genotype, lipoprotein(a) and insulin.

Combined hyperlipoproteinemia (CHL) can be difficult to treat because of the heterogeneous nature of the lipoprotein abnormalities. We compared the relative efficacies of simvastatin and gemfibrozil and sought predictors of responsiveness in terms of the baseline lipids and other potential metabolic determinants (plasma insulin, Lp(a) and apo E genotype). Sixty-six subjects entered a cross-over, randomized trial involving 12 weeks on each drug. Efficacy was assessed after 6 and 12 weeks on each treatment. Simvastatin lowered total cholesterol 24%, triglycerides 12%, LDL cholesterol 33%, raised HDL cholesterol 13% and substantially reduced the cholesterol:triglyceride ratio in VLDL and IDL. Gemfibrozil lowered total cholesterol 5%, triglycerides 44%, raised HDL 26% and reduced VLDL and IDL lipids more than simvastatin did. LDL size increased with both treatments and HDL size increased with simvastatin. Responsiveness (25% fall in cholesterol or 40% fall in triglycerides) was shown by 31/61 subjects when taking simvastatin (cholesterol-lowering) and by 44/60 taking gemfibrozil (triglyceride-lowering). Responsiveness was greatest in those with apo E2 genotype with both drugs (P < 0.05). Unexpectedly, responders to simvastatin tended to have lower baseline total cholesterol but higher triglyceride levels than those whose cholesterol or triglyceride was lowered by gemfibrozil. Nevertheless, more hypercholesterolemic subjects responded to simvastatin and more hypertriglyceridemic subjects to gemfibrozil. Lp(a) (P = 0.04) and plasma insulin concentrations (P = 0.03) were negative predictors of percentage triglyceride-lowering with gemfibrozil. The difference between the two drugs in triglyceride-lowering lessened with rising insulin and falling HDL cholesterol. Thus, the responsiveness to the two major classes of lipid lowering drugs can be partly predicted from baseline lipids and related metabolic parameters.

A profile of heart disease risk factors and their relation to parents' education, fathers' occupation and family history of heart disease in 843 South Australian families: the Adelaide Children's WHO Collaborative Study.

OBJECTIVE: A study was conducted to determine whether the prevalence of risk factors among pre-adolescent children is associated with their parents' risk factor status and what influence family history of ischaemic heart disease (IHD) and socio-economic status (SES) had. METHODOLOGY: This was a cross-sectional study of 856 children, mean age 8.6 years, and their parents who underwent the World Health Organization and National Heart Foundation protocols for the study of arteriosclerosis precursors. Historical, demographic, anthropometric, clinical and biochemical outcome measures were used. RESULTS: There was the expected burden of illness reported for the grandparents and parents, with the latter conforming to their expected age group's heart disease risk factor status. The mean serum total cholesterol (TC) level for boys was 4.43 (+/- 0.79) mmol/L and girls 4.62 (+/- 0.84) mmol/L, with the 95th percentile for boys and girls combined being 5.88 mmol/L. The level corresponding to two standard deviations above the mean was 6.0 mmol/L. Childrens' IHD risk factor status reflected their parents' with TC, skin fold thickness and body mass index most closely correlated, followed by blood pressure. The greatest correlation was between the childrens' TC and their mothers'. Socio-economic status as assessed by the parents' education level and fathers' occupational status produced differences in their childrens' risk factors, with mother's level of education having the major influence. There was no impact of family history of IHD. CONCLUSIONS: From these results it would appear that screening of the pre-adolescent may be appropriate but longitudinal study will be important to establish this by documenting persistence of risk factor status. Also, it would appear that a child's future risk from IHD morbidity may be due to environmental influences mediated through differences in SES. As the level of IHD risk factors is reduced within the community, the extent of parent-child transmission of measurable IHD risk factors in families of high IHD risk may be reduced.