scholarly journals Familial Defective Apolipoprotein B-100: A Study of Patients from Lipid Clinics in Scotland and Wales

Author(s):  
Philip R Wenham ◽  
Peter Bloomfield ◽  
Gillian Blundell ◽  
Michael D Penney ◽  
Peter W H Rae ◽  
...  

Familial defective apolipoprotein (apo) B-100 (FDB) is an autosomal codominant disorder, which may be associated with hypercholesterolaemia. The defect is caused by the substitution of glutamine for arginine at amino acid residue 3500 of apo B-100. A total of 357 hypercholesterolaemic patients, 48 with a clinical diagnosis of familial hypercholesterolaemia attending lipid clinics in Scotland and Wales, were screened for the presence of FDB. Seven unrelated individuals, five of whom had a family history of coronary heart disease, and a further 11 first-degree relatives, were shown to be heterozygous for the mutation. Pedigree analysis demonstrated the mutation to be present on a single haplotype, suggesting that in Britain it is inherited from a common ancestor. Treatment of 11 heterozygous individuals with lipid-lowering medication showed falls in total and low density lipoprotein cholesterol ranging from 11·6 to 38·8% and 5·3 to 49·5%, respectively. In view of the condition's association with coronary heart disease and hypercholesterolaemia, it may be worthwhile identifying carriers attending lipid clinics, so that affected siblings can be offered cholesterol-lowering treatment where necessary.

2018 ◽  
Vol 25 (18) ◽  
pp. 1950-1963 ◽  
Author(s):  
Kian-Keong Poh ◽  
Baishali Ambegaonkar ◽  
Carl A Baxter ◽  
Philippe Brudi ◽  
Wacin Buddhari ◽  
...  

Background As mortality due to cardiovascular disease increases throughout the world, accurate data on risk factors such as hyperlipidemia are required. This is lacking in the Asia-Pacific region. Design The observational Dyslipidemia International Study (DYSIS) II was established to quantify the extent of hyperlipidemia in adults with acute and stable coronary heart disease globally. Methods Patients with stable coronary heart disease or hospitalised with an acute coronary syndrome were enrolled across nine Asia-Pacific countries from July 2013 to October 2014. Lipid-lowering therapy and low-density lipoprotein cholesterol target attainment (<70 mg/dL) were assessed. The acute coronary syndrome cohort was followed up 4 months post-discharge. Results Of the 4592 patients enrolled, 2794 had stable coronary heart disease and 1798 were admitted with an acute coronary syndrome. In the coronary heart disease cohort, the mean low-density lipoprotein cholesterol level was 86.9 mg/dL, with 91.7% using lipid-lowering therapy and 31% achieving low-density lipoprotein cholesterol of less than 70 mg/dL. In the acute coronary syndrome cohort at admission, the corresponding values were 103.2 mg/dL, 63.4% and 23.0%, respectively. Target attainment was significantly higher in lipid-lowering therapy-treated than non-treated patients in each cohort (32.6% vs. 12.9% and 31.1% vs. 9.0%, respectively). Mean atorvastatin-equivalent dosages were low (20 ± 15 and 22 ± 18 mg/day, respectively), with little use of non-statin adjuvants (13.0% and 6.8%, respectively). Low-density lipoprotein cholesterol target attainment had improved by follow-up for the acute coronary syndrome patients, but remained low (41.7%). Conclusions Many patients in Asia at very high risk of recurrent cardiovascular events had a low-density lipoprotein cholesterol level above the recommended target. Although lipid-lowering therapy was common, it was not used to its full potential.


Author(s):  
Karl J. Krobot ◽  
Donald D. Yin ◽  
Evo Alemao ◽  
Elisabeth Steinhagen-Thiessen

Background Determinants of the real-world effectiveness of lipid-lowering therapy have been rarely assessed in an unselected observational coronary heart disease (CHD) community cohort over time. Design Randomly drawn patients (n = 605) from randomly drawn practices (n = 62) were retrospectively followed for a median of 3.6 years (1998-2002) on lipid-lowering therapy (98% statins). Methods Coronary heart disease population-averaged estimates and variances accounting for repeated measurements within patients were obtained using generalized estimating equations. Results Post-treatment low-density lipoprotein-cholesterol (LDL-C) was 124 mg/dl in men and 141 mg/dl in women and was independently associated (all P<0.05) with pre-treatment LDL-C (+ 3.7 mg/dl per 10 mg/dl increment), female sex (+ 14.0 mg/dl), coronary bypass (-9.5 mg/dl), drug-treated diabetes mellitus (-6.8 mg/dl), and era 2002/2001 versus 1999/2000 (- 6.4 mg/dl) in age-adjusted multivariate analyses. Holding pre-treatment LDL-C constant post-treatment LDL-C was associated with pre-treatment Framingham CHD risk in men (- 13.9 mg/dl per doubling of risk), whereas LDL-C control in women resembled that in low-risk men. The likelihood of attaining LDL-C < 100 mg/dl was 0.28 in men and 0.17 in women and was likewise associated with the above factors. Conclusion Low-density lipoprotein-cholesterol control remained low despite lipid-lowering therapy across a wide range of pre-treatment LDL-C and pre-treatment CHD risk. Low-density lipoprotein-cholesterol control in women was inferior to that in men, a finding that warrants attention and clarification. Eur J Cardiovasc Prev Rehabil 12:37-45 © 2005 The European Society of Cardiology


2012 ◽  
Vol 15 (3) ◽  
pp. 292-308 ◽  
Author(s):  
Christopher C. Imes ◽  
Melissa A. Austin

Coronary heart disease (CHD) affects 17 million people in the United States and accounts for over a million hospital stays each year. Technological advances, especially in genetics and genomics, have changed our understanding of the risk factors for developing CHD. The purpose of this article is to review low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and risk of CHD. The article focuses on five topics: (1) a description of lipoprotein classes, normal lipoprotein metabolism, and the biological mechanism of atherosclerosis; (2) a review of selected epidemiologic and clinical trial studies examining the associations between elevated LDL-C and apo B with CHD; (3) a brief review of the familial forms of hyperlipidemia; (4) a description of variants in genes that have been associated with higher LDL-C levels in candidate gene studies and genome-wide association studies (GWAS); and (5) nursing implications, including a discussion on how genetic tests are evaluated and the current clinical utility and validity of genetic tests for CHD.


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