Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).

These data suggest that common variation in ABCA1 significantly influences plasma lipid levels and the severity of CAD.

I n 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). 1 Since then, new evidence has emerged that has important implications for clinical practice. Large epidemiology studies and risk profiles for AKI have become available in adults and children, such as the AKI-Epidemiologic Prospective Investigation (AKI-EPI) study, 2 the 0by25 Initiative, 3 the Southeast Asia-AKI (SEA-AKI) study, 4 and the Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) 5 and Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) 6 studies. The effectiveness of the KDIGO recommendations in preventing AKI has been confirmed in small single-center randomized controlled trials (RCTs), such as the Prevention of AKI (PrevAKI) 7 and the

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Background: Familial hypercholesterolemia is a common lipid disorder that predisposes to premature cardiovascular disease. Lipid-lowering treatment of affected individuals is widely advocated, and maximum benefit can be obtained if medication is started early. A screening program for familial hypercholesterolemia is ongoing in the Netherlands since 1994. To assess the extent of treatment and therapy compliance, patients were followed up for 2 years after the diagnosis was established.Methods: Data were obtained by questionnaire. The 747 patients with familial hypercholesterolemia participating in the study were from the general community, and 62.4% were not receiving cholesterol-lowering medication.Results: The overall percentage of treated patients had risen from 37.6% at screening to 92.5% 1 year later and then decreased to 85.9% 2 years after screening. During follow-up, 6.4% of patients discontinued their medica-(REPRINTED) ARCH INTERN MED/ VOL 163, JAN 13, 2003 WWW.ARCHINTERNMED.COM 65

In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol -phytostanol mixture, containing 18 % (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1·8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet. Plasma total and LDL-cholesterol levels were statistically significantly reduced by 6·4 % (2 0·44 mmol/l) and 10·3 % (2 0·49 mmol/l), respectively, after 4 weeks of phytosterol-enriched-chocolate treatment. Plasma HDL-cholesterol and triacylglycerol levels were not affected. Consumption of phytosterol-enriched chocolates significantly increased plasma lathosterol concentration (+20·7 %), reflecting an increased endogenous cholesterol synthesis in response to phytosterol-induced decreased intestinal cholesterol absorption. Furthermore, the chocolates enriched with phytosterols significantly increased both plasma sitosterol (+95·8 %) and campesterol (+64·1 %) levels, compared with the placebo chocolate group. However, the absolute values of plasma sitosterol and campesterol remained within the normal range, that is, below 10 mg/ l. The chocolates with phytosterols were palatable and induced no clinical or biochemical side effects. These findings indicate that dietary chocolate enriched with tall oil-derived phytosterols (1·8 g/d) is effective in lowering blood total and LDL-cholesterol levels in subjects with mild hypercholesterolaemia and thus may be helpful in reducing the risk of CHD in these individuals. Phytosterols: Lipids: ChocolateRecent studies have convincingly shown that serum total and LDL-cholesterol reduction significantly decreases total and coronary mortality in primary and especially secondary prevention of CHD (Scandinavian Simvastatin Survival Study Group, 1994; Shephard et al. 1995). Dietary modification can reduce cholesterol levels and the risk of CHD, but for a significant portion of the population, treatment with lipid-lowering agents is required for effective cholesterol reduction. There is an urgent clinical need for a low-cost, low-risk intervention that can treat those individuals that have not responded well to dietary modification, and where pharmaceutical intervention is not desirable. Consumption of foods containing phyto-(i.e. plant) sterols has the necessary characteristics to meet that need.There has been renewed interest in the use of phytosterols for the treatment of hypercholesterolaemia, since they have potent cholesterol-lowering effects, as shown in normo-and hypercholesterolaemic men and women with or without CHD (Miettinen et al.