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.

Nephrotoxicity from non-steroidal anti-in ammatory 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 1 (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. Case reportA 28-year-old woman presented to the emergency department with a 2-day history of severe generalized weakness. She was unable to stand up or hold her neck straight. She said that she had one episode of vomiting on the day before admission and that, 2 weeks earlier, she had bronchitis for which her general practitioner prescribed amoxycillin. She was taking pantoprazole for a duodenal ulcer, diagnosed 7 months earlier. She was also taking over-the-counter analgesics for relapsing knee pains. She had a history of depression and alcohol dependence for which she had previously received psychiatric counselling.On examination, she was afebrile (36¢78C), her pulse rate was 90 per min, regular, and blood pressure 110/60 mmHg. She had severe generalized muscle weakness but no neurological de¢cit. Body mass index was 20¢4 kg/m 2 . The ECG showed prolonged QT intervals and inverted T waves.Blood tests on admission, showed serum potassium 1Í4 mmol/L (3Í6-5Í3), sodium 141 mmol/L (138-146), urea 6Í4 mmol/ L (2Í5-7Í5), creatinine 64 mmol/L (50-130), calcium 2Í54 mmol/ L (2Í2-2Í6) and phosphate 0Í43 mmol/ L (0Í8-1Í4). Further investigations revealed serum bicarbonate 14Í7 mmol/ L (21-28), chloride 112 mmol/ L (96-104) and an anion gap of 15Í7 mmol/L (12-16). Urinary potassium was inappropriately high at 26Í6 mmol/ L and the renal tubular maximum reabsorption of phosphate (TmP/GFR) was low at 0 Í31mmol/ L GFR (0 Í8-1Í4).In view of the hypokalaemia, hyperchloraemia, low serum bicarbonate and normal anion gap, the diagnosis of renal tubular acidosis was made. She was treated with intravenous potassium therapy over the following 4 days (a total of 340 mmol) and her serum potassium rose gradually to 3Í7 mmol/ L and bicarbonate to 23Í9 mmol/ L by day 4; 2 days later, and without any further treatment, her serum potassium was 4Í9 mmol/ L and bicarbonate 26Í5 mmol/ L. The TmP/GFR was normal (1Í4 mmol/ L GFR) and the fractional excretion of bicarbonate was 1%. An ammonium chloride acidi¢cation test was undertaken but was inconclusive because she vomited shortly after ingesting the ammonium chloride.A review of her notes revealed that, 8 months earlier, she was admitted to hospital with an episode of abdominal pain and diarrhoea. Her serum potassium at the time was 2Í4 mmol/ L and had normalized with intravenous and oral potassium. Her hypokalaemia was thought to be due to the diarrhoea and she...

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 FPG concentration followed by selective measurement of HbA1c in patients who are at high risk of developing diabetes may represent a reasonable approach to identifying patients requiring an OGTT.