Prevalence and Outcomes of Familial Hypercholesterolemia Patients in a Chinese Myocardial Infarction Cohort
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Background and aims: Familial Hypercholesterolemia (FH) is an inherited metabolic disorder with increased LDL-C levels and coronary heart disease (CHD) risk. The prevalence of heterozygous FH is approximately 1:200 to 1:500 worldwide and higher in CHD populations. We aim to estimate the prevalence of FH and the incidence of recurrent cardiovascular events among FH and non-FH patients in a large myocardial infarction cohort in China.
Methods: We studied the cohort from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective study (PEACE-Prospective). The eligible cohort included 3367 patients hospitalized for myocardial infarction (MI).
Results: The proportion of potential FH was 0.80% and 4.28% by Dutch Lipid Clinic Network (DLCN) and modified DLCN criteria, respectively. Compared to non-FH, the FH patients were younger, having more personal and family history of premature CHD, current smokers and overweight. The exome sequencing identified 11 cases of pathogenic variants on LDL receptor and ApoB. The risk of recurrent cardiovascular events after MI was greater in FH patients with a hazard ratio (HR) of 1.97 with modified DLCN.
Conclusions: The prevalence of Chinese FH by modified DLCN is comparable to the European estimate by DLCN in the high cardiovascular risk cohort. The patients with FH compared to non-FH have an almost 2-fold adjusted risk of recurrent cardiovascular events. Further consensus on the LDL-C-based threshold may help on the establishment of country specific criteria for FH.Cite
Familial hypercholesterolaemia (FH) is the most common autosomal dominant condition, with a prevalence of between one in 200 and one in 350 people in the general population. Untreated FH is associated with premature atherosclerotic cardiovascular disease (CVD). The prevalence of homozygous or compound heterozygous FH is now considered to be about one in 300 000 people. Treating children with FH reduces progression of atherosclerotic CVD and future CVD events. Most individuals with FH are undiagnosed, which together with the recent frequency data in the population and in individuals with premature coronary disease creates a public health challenge and mandates a key role for primary care. Childhood is the optimal period for detecting FH, since low-density lipoprotein cholesterol (LDL-c) concentrations better differentiate affected from unaffected individuals. In an Australian community setting, over 70% of adults with an LDL-c level ≥ 6.5 mmol/L have clinical FH; of these, 30% have a detectable mutation. The community laboratory has an important role in identifying FH, with interpretive comments leading to additional reductions in LDL-c concentrations, and a phone call from the pathologist to the general practitioner improving detection of cases. Cascade screening using DNA testing is cost-effective and acceptable to screenees. Next generation genetic sequencing may differentiate people with polygenic hypercholesterolaemia alone from those with FH. Smoking, hypertension, elevated lipoprotein(a) levels, chronic kidney disease and diabetes are additional atherosclerotic CVD risk factors in FH. Equations for assessing absolute risk of CVD in primary prevention underestimate risk in FH. The adult LDL-c goal is a greater than 50% reduction in LDL-c levels, followed by a target of < 2.5 mmol/L, or < 1.8 mmol/L for individuals with CVD or other CVD risk factors. Proprotein convertase subtilisin/kexin type 9 inhibitors significantly reduce LDL-c and lipoprotein(a) levels in people with FH. Registries are essential for improving the care of people with FH.
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Stroke
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Heterozygous familial hypercholesterolaemia (FH) is a common autosomal dominant disorder. The vast majority of affected individuals remain undiagnosed, resulting in lost opportunities for preventing premature heart disease. Better use of routine primary care data offers an opportunity to enhance detection. We sought to develop a new predictive algorithm for improving identification of individuals in primary care who could be prioritised for further clinical assessment using established diagnostic criteria.Data were analysed for 2,975,281 patients with total or LDL-cholesterol measurement from 1 Jan 1999 to 31 August 2013 using the Clinical Practice Research Datalink (CPRD). Included in this cohort study were 5050 documented cases of FH. Stepwise logistic regression was used to derive optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy (area under receiver operating curve [AUC]).The FH prediction model (FAMCAT), consisting of nine diagnostic variables, showed high discrimination (AUC 0.860, 95% CI 0.848-0.871) for distinguishing cases from non-cases. Sensitivity analysis demonstrated no significant drop in discrimination (AUC 0.858, 95% CI 0.845-0.869) after excluding secondary causes of hypercholesterolaemia. Removing family history variables reduced discrimination (AUC 0.820, 95% CI 0.807-0.834), while incorporating more comprehensive family history recording of myocardial infraction significantly improved discrimination (AUC 0.894, 95% CI 0.884-0.904).This approach offers the opportunity to enhance detection of FH in primary care by identifying individuals with greatest probability of having the condition. Such cases can be prioritised for further clinical assessment, appropriate referral and treatment to prevent premature heart disease.
Stepwise regression
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The purpose of the study was to evaluate the effects of Allicor, an Allium sativum (garlic) preparation with prolonged activity, on 10-year prognostic risk of coronary heart disease (CHD), acute myocardial infarction (MI) and sudden death in patients with elevated and high risk of CHD. 79 patients with elevated and high risk of CHD were included in a double blind randomized placebo-controlled study. They underwent multifactor evaluation of cardiovascular risk by algorithms based on the results of Framingham and Munster studies. Prolonged (12 months) administration of Allicor significantly reduced the multifactor risk, which was demonstrated by a 13.2% (p = 0.005) reduction of prognostic 10-year risk of CHD in men, and a 7.1% (p = 0.040) reduction of the same parameter in women. Prognostic 10-year risk of MI and sudden death in men was reduced by 26.1% (p = 0.025) and did not change significantly in women. In men the main factor of cardiovascular risk reduction was the decrease of cholesterol and low-density lipoprotein concentration by 23.5 +/- 6.6 mg/dl (p = 0.004), and in women - the increase of high-density lipoprotein level by 2.8 +/- 1.5 mg/dl (p = 0.040). The results of the study demonstrate that prolonged Allicor therapy can be applied to the large category of patients who are in need of atherosclerosis prevention.
Sudden Death
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Background and Purpose— Familial hypercholesterolemia (FH) is a common autosomal dominant disease leading to increased level of serum LDL (low-density lipoprotein) cholesterol and risk of coronary heart disease. Whether FH increases the risk of cerebrovascular disease, including ischemic stroke, is debated. Accordingly, we studied the incidence of cerebrovascular disease in a cohort of people with genetically verified FH compared with the entire Norwegian population and examined whether people in this cohort with previous cohort had increased risk of cerebrovascular disease. Methods— Incidence rates of hospitalization for cerebrovascular disease (among 3144 people with FH) and ischemic stroke (among 3166 people with FH) were estimated by linkage of FH people to Cardiovascular Disease in Norway—a nationwide database of cardiovascular disease hospitalizations (2001–2009). We calculated standardized incidence ratios and used Cox regression to estimate hazard ratios. Results— A total of 46 cases (19 women and 27 men) of cerebrovascular disease were observed in the cohort of people with FH, with no increased risk of cerebrovascular disease compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.8–1.4). Total number of ischemic strokes in the cohort of people with FH was 26 (9 women and 17 men), with no increased risk compared with the general population (standardized incidence ratio, 1.0; 95% CI, 0.7–1.5). Prior coronary heart disease significantly increased cerebrovascular disease risk in women (hazard ratio, 3.29; 95% CI, 1.20–9.00) but not in men (hazard ratio, 1.03; 95% CI, 0.45–2.37; P interaction =0.04). Conclusions— In a large cohort of genetically verified FH, risks of cerebrovascular disease and ischemic stroke were not increased compared with the total Norwegian population.
Stroke
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Hyperlipidemia
Lipoprotein(a)
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Familial hypercholesterolaemia (FH) is a well-defined but underdiagnosed dyslipidaemia occurring in 1:500 persons. We report a case where an 18-year-old woman with an untreated FH dies a sudden cardiac death due to acute myocardial infarction. In patients with FH atherosclerotic manifestations are common at a young age and FH should always be suspected in patients with P-low-density lipoprotein cholesterol level above 5 mmol/l (4 mmol/l for persons < 16 years of age). Patients with FH should be referred to specialized units so that family members with FH systematically are identified.
Sudden Death
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Atherosclerotic cardiovascular disease
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Objectives Whereas the importance of family history (FH) is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based definition (cFH): presence of premature cardiovascular disease (CVD) in a first-degree relative. We tested the added value of a new, extended family history definition (eFH), also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population. Design longitudinal population study. Setting random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care). Subjects 2524 male/female volunteers, aged 35–55 years, free from overt CVD. Main outcome measures Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound) and a newly developed FH questionnaire (4 generations). Results Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components) and presence of atherosclerosis (all age & sex-adjusted p<0.05). Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset) in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study. Conclusions A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool.
Subclinical infection
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