Background and aimsFamilial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. We assessed the degree of preclinical atherosclerosis in treated patients with monogenic FH versus polygenic hypercholesterolemia.MethodsFH mutation testing and genotypes of six LDL-C-associated single nucleotide polymorphisms (SNPs) were determined using routine methods. Those with a detected mutation (monogenic) and mutation-negative patients with LDL-C SNP score in the top two quartiles (polygenic) were recruited. Carotid intima media thickness (IMT) was measured by B-mode ultrasound and the coronary artery calcium (CAC) score was performed in three lipid clinics in the UK and the Netherlands.Results86 patients (56 monogenic FH, 30 polygenic) with carotid IMT measurement, and 166 patients (124 monogenic, 42 polygenic) with CAC score measurement were examined. After adjustment for age and gender, the mean of all the carotid IMT measurements and CAC scores were significantly greater in the monogenic than the polygenic patients [carotid IMT mean (95% CI): 0.74 mm (0.7–0.79) vs. 0.66 mm (0.61–0.72), p = 0.038 and CAC score mean (95%): 24.5 (14.4–41.8) vs. 2.65 (0.94–7.44), p = 0.0004].ConclusionsIn patients with a diagnosis of FH, those with a monogenic cause have a higher severity of carotid and coronary preclinical atherosclerosis than those with a polygenic aetiology.
Summary Aims To develop an estimation of risk of coronary heart disease (CHD) based on the Framingham equation for use in a diabetes clinic, given concerns about the accuracy of the Sheffield risk tables in this setting. Methods A computer program using the Framingham equation based on patients’ age, sex, systolic blood pressure, smoking history, presence of diabetes and left ventricular hypertrophy was applied to requests for lipid screening of patients attending the diabetes clinics of Birmingham Heartlands Hospital. The calculated risks for the population were compared with those estimated from the Sheffield tables. Results Of 1060 patients with diabetes mellitus, 215 (20%) had an annual CHD risk ≥ 3%, which is considered to be the threshold at which lipid‐lowering drugs are cost‐effective. Only 24 of these 215 patients (11%) were correctly identified by the Sheffield tables, which we conclude have an unacceptably low sensitivity in diabetes mellitus. Conclusions A laboratory‐based CHD risk calculation system is a practical alternative to the Sheffield system and may have a greater sensitivity in the diabetic clinic.
The use of anabolic steroids in sport and exercise appears to have increased in recent years and their use is no longer restricted to elite athletes. 1,2 A recent survey in private gymnasia in West Glamorgan showed that over 80% of subjects taking steroids were engaged in body building and power lifting and II·3% of users were only engaged in fitness exercises.' Anabolic steroids have been shown to adversely affect the lipid profile and their use should be considered in young 'healthy' persons with abnormal lipid profiles, particularly those with low high-density lipoprotein (HDL)-cholesterol concentrations.
Nephrotoxicity from non-steroidal anti-inflammatory drugs (NSAID) is well recognized. We report a case of severe hypokalaemia and weakness due to renal tubular acidosis in a young woman who was taking 40-60 tablets per day of Nurofen Plus ® (ibuprofen 200 mg and codeine phosphate 12·8 mg). Proprietary brands of ibuprofen are freely available to the public and those containing codeine may be potentially subject to abuse. This case highlights the need to be aware of this potential and of the life-threatening electrolyte and acid-base disturbances that might be encountered with the widespread availability of these types of NSAID.
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