Familial Hypercholesterolemia, Familial Combined Hyperlipidemia, and Elevated Lipoprotein(a) in Patients With Premature Coronary Artery Disease.
TL;DR: FH, FCHL and elevated Lp(a) are common in patients with premature CAD and differently impact treatment and achievement of lipid targets, which provides valuable information for individualized management.
About: This article is published in Canadian Journal of Cardiology.The article was published on 2021-08-26. It has received 8 citations till now. The article focuses on the topics: Familial hypercholesterolemia & Lipoprotein(a).
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TL;DR: Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years as mentioned in this paper , and coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement.
17 citations
TL;DR: In this article , a unified definition and mechanism-based classification of hypercholesterolemia was proposed, which in turn should help to stratify patients and guide efficient diagnosis without interfering with the current strategies of ASCVD risk reduction.
9 citations
TL;DR: In this article, the LDL receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH).
5 citations
TL;DR: The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions in heterozygous familial hypercholesterolemia (HeFH) as discussed by the authors .
5 citations
TL;DR: In a cohort of newly diagnosed, untreated, insulin-sensitive FCH patients, a high prevalence of liver steatosis was found and the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis.
Abstract: Familial combined hyperlipidemia (FCH) is a very common inherited lipid disorder, characterized by a high risk of developing cardiovascular (CV) disease and metabolic complications, including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The prevalence of non-alcoholic fatty liver disease (NAFLD) is increased in FCH patients, especially in those with IR or T2DM. However, it is unknown how precociously metabolic and cardiovascular complications appear in FCH patients. We aimed to evaluate the prevalence of NAFLD and to assess CV risk in newly diagnosed insulin-sensitive FCH patients. From a database including 16,504 patients, 110 insulin-sensitive FCH patients were selected by general practitioners and referred to the Lipid Center. Lipid profile, fasting plasma glucose and insulin were determined by standard methods. Based on the results of the hospital screening, 96 patients were finally included (mean age 52.2 ± 9.8 years; 44 males, 52 females). All participants underwent carotid ultrasound to assess carotid intima media thickness (cIMT), presence or absence of plaque, and pulse wave velocity (PWV). Liver steatosis was assessed by both hepatic steatosis index (HSI) and abdomen ultrasound (US). Liver fibrosis was non-invasively assessed by transient elastography (TE) and by fibrosis 4 score (FIB-4) index. Carotid plaque was found in 44 out of 96 (45.8%) patients, liver steatosis was found in 68 out of 96 (70.8%) and in 41 out of 96 (42.7%) patients by US examination and HSI, respectively. Overall, 72 subjects (75%) were diagnosed with steatosis by either ultrasound or HSI, while 24 (25%) had steatosis excluded (steatosis excluded by both US and HSI). Patients with liver steatosis had a significantly higher body mass index (BMI) compared to those without (p < 0.05). Steatosis correlated with fasting insulin (p < 0.05), liver stiffness (p < 0.05), BMI (p < 0.001), and inversely with high-density lipoprotein cholesterol (p < 0.05). Fibrosis assessed by TE was significantly associated with BMI (p < 0.001) and cIMT (p < 0.05); fibrosis assessed by FIB-4 was significantly associated with sex (p < 0.05), cIMT (p < 0.05), and atherosclerotic plaque (p < 0.05). The presence of any grade of liver fibrosis was significantly associated with atherosclerotic plaque in the multivariable model, independent of alcohol habit, sex, HSI score, and liver stiffness by TE (OR 6.863, p < 0.001). In our cohort of newly diagnosed, untreated, insulin-sensitive FCH patients we found a high prevalence of liver steatosis. Indeed, the risk of atherosclerotic plaque was significantly increased in patients with liver fibrosis, suggesting a possible connection between liver disease and CV damage in dyslipidemic patients beyond the insulin resistance hypothesis.
2 citations
References
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TL;DR: Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions.
10,387 citations
TL;DR: To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations.
Abstract: ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.
2,234 citations
TL;DR: The combined disorder was shown to be genetically distinct from familial hypercholesterolemia and familial hypertriglyceridemia for the following reasons: the distribution pattern of cholesterol and triglyceride levels in relatives of probands was unique.
Abstract: To assess the genetics of hyperlipidemia in coronary heart disease, family studies were carried out in 2520 relatives and spouses of 176 survivors of myocardial infarction, including 149 hyperlipidemic and 27 normolipidemic individuals. The distribution of fasting plasma cholesterol and triglyceride values in relatives, together with segregation analyses, suggested the presence of five distinct lipid disorders. Three of these-familial hypercholesterolemia, familial hypertriglyceridemia, and familial combined hyperlipidemia-appeared to represent dominant expression of three different autosomal genes, occurring in about 20% of survivors below 60 yr of age and 7% of all older survivors. Two other disorders-polygenic hypercholesterolemia and sporadic hypertriglyceridemia-each affected about 6% of survivors in both age groups. The most common genetic form of hyperlipidemia identified in this study has hitherto been poorly defined and has been designated as familial combined hyperlipidemia. Affected family members characteristically had elevated levels of both cholesterol and triglyceride. However, increased cholesterol or increased triglyceride levels alone were also frequently observed. The combined disorder was shown to be genetically distinct from familial hypercholesterolemia and familial hypertriglyceridemia for the following reasons: (a) the distribution pattern of cholesterol and triglyceride levels in relatives of probands was unique; (b) children of individuals with combined hyperlipidemia did not express hypercholesterolemia in contrast to the finding of hypercholesterolemic children from families with familial hypercholesterolemia; and (c) analysis of informative matings suggested that the different lipid phenotypes owed their origin to variable expression of a single autosomal dominant gene and not to segregation of two separate genes, such as one elevating the level of cholesterol and the other elevating the level of triglyceride. Heterozygosity for one of the three lipid-elevating genes identified in this study may have a frequency in the general population of about 1%, constituting a major problem in early diagnosis and preventive therapy.
1,409 citations
TL;DR: High levels of lipoprotein(a) are associated with increased risk of myocardial infarction (MI), but whether genetic data are consistent with this association being causal is not known.
Abstract: Context High levels of lipoprotein(a) are associated with increased risk of myocardial infarction (MI). Objective To assess whether genetic data are consistent with this association being causal. Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a prospective general population study with 16 years of follow-up (1991-2007, n = 8637, 599 MI events); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (2003-2006, n = 29 388, 994 MI events); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (1991-2004, n = 2461, 1231 MI events). Main Outcome Measures Plasma lipoprotein(a) levels, lipoprotein(a) kringle IV type 2 (KIV-2) size polymorphism genotype, and MIs recorded from 1976 through July 2007 for all participants. Results In the CCHS, multivariable-adjusted hazard ratios (HRs) for MI for elevated lipoprotein(a) levels were 1.2 (95% confidence interval [CI], 0.9-1.6; events/10 000 person-years, 59) for levels between the 22nd and 66th percentile, 1.6 (95% CI, 1.1-2.2; events/10 000 person-years, 75) for the 67th to 89th percentile, 1.9 (95% CI, 1.2-3.0; events/10 000 person-years, 84) for the 90th to 95th percentile, and 2.6 (95% CI, 1.6-4.1; events/10 000 person-years, 108) for levels greater than the 95th percentile, respectively, vs levels less than the 22nd percentile (events/10 000 person-years, 55) (trend P Conclusion These data are consistent with a causal association between elevated lipoprotein(a) levels and increased risk of MI.
1,021 citations
University of Calgary1, Montreal Heart Institute2, University of Alberta3, Laval University4, University of British Columbia5, McGill University Health Centre6, McGill University7, University of Toronto8, McMaster University9, Robarts Research Institute10, Population Health Research Institute11, University of Ottawa12, Alberta Health Services13
TL;DR: Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age, and recommendation for the use of nonstatin medications is provided.
805 citations