Prevalence of familial hypercholesterolemia phenotype in working population and incidence of cardiovascular events

Background and aims: Elevated lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease especially in familial hypercholesterolemia. The association of elevated lipoprotein(a) within non-familial hypercholesterolemia or healthy population however, is not known. Therefore, we investigated the associations between elevated lipoprotein(a) and the risk of cardiovascular disease in a non-familial hypercholesterolemia clinically healthy young age cohort. Methods: In this retrospective cohort study, we reviewed medical records of 3,427 participants with lipoprotein(a) levels from a tertiary healthcare center in Taiwan. We further classified lipoprotein(a) level into four groups and analyzed cardiovascular events. Results: Our study population had a mean age 46 years old that were 78% male. Mean total cholesterol and low-density lipoprotein level were 195 mg/dL and 118 mg/dL respectively. Overall, 12.9% of the participants had an elevated lipoprotein(a) level (>30 mg/dL), and 2.7% had a very high level (>70 mg/dL). Thirty-three events including 6 participants with stroke and 27 with coronary artery disease were identified. A lipoprotein(a) level >70 mg/dL was associated with a higher risk of coronary artery disease events in Kaplan-Meier analysis. Aging was associated with a higher lipoprotein(a) value in the male participants but not in the female participants. However, the severity of fatty liver was not positively associated with lipoprotein(a) value. Conclusions: Elevated lipoprotein(a) was associated with coronary events but not the severity of fatty liver disease in non-familial hypercholesterolemia clinically healthy population. Aging may be associated with a higher lipoprotein(a) level in males but not females.

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Differences in phenotype, genotype and cardiovascular events between patients with probable and definite heterozygous familial hypercholesterolemia

Personalized Medicine ◽

10.2217/pme-2018-0135 ◽

2019 ◽

Vol 16 (6) ◽

pp. 467-478

Author(s):

Ye-Xuan Cao ◽

Bing-Yang Zhou ◽

Di Sun ◽

Sha Li ◽

Yuan-Lin Guo ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Survival Rates ◽

Gene Mutations ◽

Density Lipoprotein ◽

Heterozygous Familial Hypercholesterolemia ◽

Lipid Clinic ◽

Kaplan Meier

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan–Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

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Prevalence, clinical characteristics and prognosis of intracranial artery atherosclerosis in heterozygous familial hypercholesterolemia: insights from magnetic resonance angiography imaging analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.2364 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Funabashi ◽

Y Kataoka ◽

M Hori ◽

M Ogura ◽

K Matsuki ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Triglyceride Level ◽

Cardiovascular Events ◽

Intracranial Artery ◽

Elevated Triglyceride Level ◽

Heterozygous Familial Hypercholesterolemia ◽

Significant Difference ◽

Intracranial Artery Stenosis ◽

Intracranial Arteries ◽

Relationship Of

Abstract Introduction Heterozygous familial hypercholesterolemia (HeFH) exhibits substantially atherogenic substrate which involves coronary and peripheral arteries. Whether atherosclerosis in HeFH propagates to intracranial arteries causing stroke remains to be determined. Purpose To characterize intracranial artery stenosis (IAS) in subjects with HeFH. Methods 148 HeFH subjects who underwent MRI/MRA imaging to evaluate intracranial arteries were analyzed. IAS was defined as the presence of stenosis with its % diameter stenosis ≥25%. Clinical demographics and cardiovascular events (all-cause death, ACS, stroke and PAD) were compared in those with and without IAS. Results IAS was observed in 24.3% (=36/148) of study subjects. It was more frequently located at middle cerebral artery (30.6%=11/36), followed by internal carotid artery (25.0%=9/36). 47.2% of IAS exhibited % diameter stenosis ≥75%. Furthermore, 58.3% of HeFH patients with IAS exhibited concomitance of CAD, PAD or carotid stenosis. They were more likely to be older (Table). While there was no significant difference in LDL-C level, an elevated triglyceride level was observed in those with IAS (Table). Of note, during the observational period (median=14.1 years), IAS was associated with a greater likelihood of experiencing not only stroke but other cardiovascular events (all-cause death + ACS + PAD) (picture). Multivariate analysis demonstrated triglyceride level ≥1.7mmol/l as an independent predictor of IAS in HeFH patients (HR=5.53, 95% CI: 1.85–16.5, p=0.002). Conclusions Around one-fourth of HeFH patients harboured IAS, which was associated with concomitance of atherosclerosis in other vascular beds and the occurrence of stroke and other cardiovascular events. Given the relationship of IAS with hypertriglyceridemia, this lipid feature may be an important contributor to atherosclerotic formation which involves intracranial artery in HeFH patients. Clinical outcome Funding Acknowledgement Type of funding source: None

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Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

European Heart Journal ◽

10.1093/ehjci/ehaa946.2983 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Tada ◽

H Okada ◽

A Nomura ◽

A Nohara ◽

M Yamagishi ◽

...

Keyword(s):

Risk Factors ◽

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Lipid Lowering ◽

Funding Source ◽

Atherosclerotic Cardiovascular Disease ◽

Prognostic Impact ◽

Cascade Screening ◽

Ascvd Risk ◽

The Impact

Abstract Background Early diagnosis and timely treatment for the patients with familial hypercholesterolemia (FH) can substantially lower the risk of atherosclerotic cardiovascular disease (ASCVD). In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. Objectives We aimed to evaluate the prognostic impact of cascade screening for FH. Methods We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1–17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events. Results During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P<0.001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95% CI = 0.22 to 0.60; P<0.001) when compared with the probands, even after adjusting for those known risk factors. Conclusions The identification of patients with FH via cascade screening appeared to result in better prognoses. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Scientific research grants from the Ministry of Education, Science and Culture of Japan (no. 16K19394, 18K08064, and 19K08575)

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