Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.

Objective: To analyse the psychometric properties of the EuroQol questionnaire (EQ-5D) applied to patients with acute coronary syndromes (ACS). Setting: Rehabilitation hospital. Patients and design: 106 consecutive patients with ACS (51% myocardial infarction, 42% coronary artery bypass grafting, 7% angina) completed the EQ-5D, the 36 item short form health survey (SF-36), and the MacNew questionnaire at admission, at discharge, and three months after inpatient cardiac rehabilitation. Acceptance, validity, reliability, and responsiveness of the EQ-5D were tested. Results: The EQ-5D was highly accepted. The EQ-5D index showed substantial ceiling effects after rehabilitation. As expected the EQ-5D visual analogue scale (VAS) score (70.3 v 57.1) and EQ-5D index (77.8 v 64.5) were significantly better for patients with myocardial infarction than for patients who underwent surgery (both p ( 0.001). Significant correlations were found between the EQ-5D VAS score, EQ-5D index, and domains of the SF-36 (r = 0.21 to r = 0.74). The correlation with the MacNew subscores and with the global score ranged between 0.55 and 0.78. With repeated measurement the EQ-5D showed reasonable reliability in stable patients with intraclass correlation ranging between 0.91 and 0.54. EQ-5D was responsive in patients who indicated improvement in health states between admission and discharge (effect size 0.74-0.82). Conclusion:The psychometric properties of the EQ-5D were satisfying. It is a reasonably valid, reliable, and responsive instrument for patients with ACS. It may be useful in clinical research and epidemiological studies to generate preference based valuations of health related quality life.A cute coronary syndromes (ACS) are highly prevalent in western countries. The diagnosis of ACS is associated with a high mortality and leads to increased morbidity, including chronic physical impairments and functional limitations, all of which have an impact on health related quality of life (HRQoL). HRQoL is a subjective measure of well being comprising social, mental, and physical dimensions.1

The present results indicate that the benefit of cardiac rehabilitation therapy following acute coronary events is only partially maintained during the following year. Continuous strategies of medical care need to be developed to improve the long-term outcome in coronary patients.

Objective To study the association of self-reported physical activity level with prognosis in a cohort of patients with coronary heart disease (CHD), with a special focus on the dose-response relationship with different levels of physical activity. Methods Data were drawn from a prospective cohort of 1038 subjects with stable CHD in which frequency of strenuous leisure time physical activity was assessed repeatedly over 10 years of follow-up. Multiple Cox proportional hazards regression models were used to assess the association of physical activity level with different outcomes of prognosis (major cardiovascular events, cardiovascular mortality, all-cause mortality), with different sets of adjustments for potential confounders and taking into account time-dependence of frequency of physical activity. Results A decline in engagement in physical activity over follow-up was observed. For all outcomes, the highest hazards were consistently found in the least active patient group, with a roughly twofold risk for major cardiovascular events and a roughly fourfold risk for both cardiovascular and all-cause mortality in comparison to the reference group of moderately frequent active patients. Furthermore, when taking time-dependence of physical activity into account, our data indicated reverse J-shaped associations of physical activity level with cardiovascular mortality, with the most frequently active patients also having increased hazards (2.36, 95% CI 1.05 to 5.34). Conclusions This study substantiated previous findings on the increased risks for adverse outcomes in physically inactive CHD patients. In addition, we also found evidence of increased cardiovascular mortality in patients with daily strenuous physical activity, which warrants further investigation.

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