Abstract 13328: Impact of Cascade Screening for Familial Hypercholesterolemia on Cardiovascular Events

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hayato Tada ◽  
Atsushi Nohara ◽  
Masakazu Yamagishi ◽  
Masayuki Takamura ◽  
Masa-aki Kawashiri
Keyword(s):  
Risk Factors ◽  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Prognostic Impact ◽  
Cascade Screening ◽  
Increased Risk ◽  
Ascvd Risk ◽  
The Impact

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Early diagnosis and timely treatment can substantially lower the risk of 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. 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, who were referred to our institute. 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 < 2.2 х 10 –16 ), 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 = 6.3 х 10 –5 ) 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.

Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

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&lt;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&lt;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)

Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk

2019 ◽  
Vol 26 (12) ◽  
pp. 1262-1270 ◽  
Author(s):  
Seohyuk Lee ◽  
Leo E Akioyamen ◽  
Sumayah Aljenedil ◽  
Jean-Baptiste Rivière ◽  
Isabelle Ruel ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Odds Ratio ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
The Impact

Aims Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of ‘definite familial hypercholesterolemia’, 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. Methods We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. Results After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28–80%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7–2.5% of subjects with an LDL-C > 4.9 mmol/L (190 mg/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n = 4181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75–9.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34–8.26), compared with controls. Conclusion DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change.

scholarly journals Evaluation of Cardiovascular Risk Factors in Patients With Familial Hypercholesterolemia From the North-Eastern Area of Romania

2020 ◽  
Author(s):  
Cristiana-Elena Vlad ◽  
Liliana Foia ◽  
Laura Florea ◽  
Irina-Iuliana Costache ◽  
Andreea Covic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
The North ◽  
Increased Risk ◽  
North Eastern ◽  
North Eastern Part

Abstract Background. Familial hypercholesterolemia (FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and nontraditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease (ASCVD) in this population. Objective. (a)To identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b)to identify of new cardiovascular events in FH patients throughout the follow-up based on the administrated lipid lowering drugs.Methods. This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network (DLCN) and Simon Broome (SM) scores, only 61 patients with DLCN score above 3 and possible/probable FH (SM score) were included.Results. The 61 FH subjects recorded a mean age of 48.5±12.5 years, with more female patients than male patients. Hypertension was the main cardiovascular risk factor for both sexes, followed by physical inactivity and obesity for the female FH group and active smoker for the male FH group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. After the administration of the lipid-lowering agents for 24 months, low-density cholesterol lipoprotein(LDL-C) levels and carotid intima-media thickness(cIMT) have decreased, while the ankle-brachial index(ABI) and high-density cholesterol lipoprotein(HDL-C) levels have increased. Also, the cIMT values over 0.9mm, total cholesterol(TC), triglyceride(TG), and high-sensitivity C-reactive protein(hsCRP) levels were associated with an increased risk of ASCVD. In addition, statins administrated in monotherapy have delayed de new cardiovascular events.Conclusions. To obtain a reduction of cardiovascular events, FH patients need cascade screening for early identification and a specific management with possible administration of monoclonal antibodies, despite the significant socio-economic barriers.

scholarly journals Genetics of Hypercholesterolemia: Comparison Between Familial Hypercholesterolemia and Hypercholesterolemia Nonrelated to LDL Receptor

2020 ◽  
Vol 11 ◽  
Author(s):  
Estíbaliz Jarauta ◽  
Ana Ma Bea-Sanz ◽  
Victoria Marco-Benedi ◽  
Itziar Lamiquiz-Moneo
Keyword(s):  
Cardiovascular Risk ◽  
Familial Hypercholesterolemia ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Ldl Receptor ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Single Nucleotide Variants ◽  
Cascade Screening ◽  
The Moment

Severe hypercholesterolemia (HC) is defined as an elevation of total cholesterol (TC) due to the increase in LDL cholesterol (LDL-C) &gt;95th percentile or 190 mg/dl. The high values of LDL-C, especially when it is maintained over time, is considered a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), mostly expressed as ischemic heart disease (IHD). One of the best characterized forms of severe HC, familial hypercholesterolemia (FH), is caused by the presence of a major variant in one gene (LDLR, APOB, PCSK9, or ApoE), with an autosomal codominant pattern of inheritance, causing an extreme elevation of LDL-C and early IHD. Nevertheless, an important proportion of serious HC cases, denominated polygenic hypercholesterolemia (PH), may be attributed to the small additive effect of a number of single nucleotide variants (SNVs), located along the whole genome. The diagnosis, prevalence, and cardiovascular risk associated with PH has not been fully established at the moment. Cascade screening to detect a specific genetic defect is advised in all first- and second-degree relatives of subjects with FH. Conversely, in the rest of cases of HC, it is only advised to screen high values of LDL-C in first-degree relatives since there is not a consensus for the genetic diagnosis of PH. FH is associated with the highest cardiovascular risk, followed by PH and other forms of HC. Early detection and initiation of high-intensity lipid-lowering treatment is proposed in all subjects with severe HC for the primary prevention of ASCVD, with an objective of LDL-C &lt;100 mg/dl or a decrease of at least 50%. A more aggressive reduction in LDL-C is necessary in HC subjects who associate personal history of ASCVD or other cardiovascular risk factors.

scholarly journals Family history and polygenic risk of cardiovascular disease: independent factors associated with secondary cardiovascular events in patients undergoing carotid endarterectomy

2019 ◽  
Author(s):  
Nathalie Timmerman ◽  
Dominique P.V. de Kleijn ◽  
Gert J. de Borst ◽  
Hester M. den Ruijter ◽  
Folkert W. Asselbergs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Family History ◽  
Carotid Endarterectomy ◽  
Cardiovascular Risk Factors ◽  
Cardiovascular Events ◽  
Polygenic Risk ◽  
Increased Risk ◽  
The Impact

AbstractBackgroundFamily history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA).MethodsWe included 1,788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition.ResultsPositive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p=0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p=0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p=0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p=0.006).ConclusionIn CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.

Abstract MP53: The Impact of the Obesity Epidemic on Atherosclerotic Cardiovascular Disease Risk Scores: The CARDIA Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duke Appiah ◽  
Pamela J Schreiner ◽  
Raegan W Durant ◽  
Sharina D Person ◽  
Catarina I Kiefe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Young Adults ◽  
Disease Risk ◽  
Risk Scores ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
Obesity Epidemic ◽  
Ascvd Risk ◽  
The Impact

Introduction: Cardiovascular disease (CVD) mortality has decreased over recent decades, in part, due to changes in the prevalence of risk factors. However, few studies have explored the impact of the obesity epidemic on CVD risk prediction in young adults. Hypothesis: We assessed the hypothesis that BMI trends are positively associated with changes in 10-year AHA/ACC atherosclerotic cardiovascular disease (ASCVD) risk scores from young adulthood to middle age beyond the effect of other CVD risk factors included in the scores (age, sex, race, lipids, blood pressure, hypertension medication, diabetes, smoking). METHODS: Data were obtained from 2437 black and white men and women aged 18-30 years at baseline (1985-1986) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study with follow-up exams at year 0, 5, 10, 15, 20 and 25 (ages 43-55 years). Repeated-measures regression was used to model the association between ASCVD risk scores and time-varying BMI measures. RESULTS: The average 10-year ASCVD risk increased from 0.6% at baseline (mean age: 25.3) to 3.9% at year 25 (mean age: 50.3) with the change higher for men (blacks: 1.0 to 8.2%, whites: 0.3 to 4.6%) than women (blacks: 0.5 to 3.6%, whites: 1.2 to 1.4%). The overall prevalence of obesity at baseline and year 25 was 10% and 42% respectively. BMI trends were positively associated with 10-year change in ASCVD risk scores (0.12% per 1 kg/m2 increase, p<0.001). BMI adjustment minimally reduced risk scores trends with the greatest change between unadjusted and adjusted risk scores observed among black women (0.1 to 3.0%) (Figures A and B). CONCLUSION: In young adults, BMI trends are associated positively with 10-year changes in ASCVD risk independent of other risk factors. This adds to the evidence that weight control in early adulthood is an important predictor of lower future CVD risk.

Abstract 273: HDL Particle Concentration Inversely Associates with Incident Metabolic Syndrome in the Multiethnic Dallas Heart Study

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Preethi Mani ◽  
Ian J Neeland ◽  
Darren K McGuire ◽  
Colby Ayers ◽  
Amit Khera ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Visceral Fat ◽  
Particle Concentration ◽  
Atherosclerotic Cardiovascular Disease ◽  
Heart Study ◽  
Increased Risk ◽  
Ascvd Risk ◽  
Dallas Heart Study

Objective: Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and other recognized risk factors. Methods: HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30-65. Participants with prevalent MetS, DM, CVD, cirrhosis, cancer, HIV, or renal failure were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 9.4 years. Results: Among a cohort of 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r=0.54, p<0.0001). The lowest quartile of HDL-P was associated with younger age, men, Hispanic ethnicity, lower total, HDL, and LDL cholesterol levels and particle sizes, and less reported alcohol intake. Participants in the lowest sex and race stratified quartile of HDL-P had the highest incidence of MetS (Figure). In models adjusted for traditional risk factors, HDL-C, visceral fat, HOMA-IR, and hs-CRP, the lowest quartile of HDL-P was associated with 65% increased risk of incident MetS (Figure). Conclusion: HDL-P is independently associated with incident MetS after adjustment for HDL-C, adiposity, inflammation, and markers of insulin sensitivity. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association.

scholarly journals Evaluation of Cardiovascular Risk Factors In Patients With Familial Hypercholesterolemia From The North-Eastern Area of Romania

2020 ◽  
Author(s):  
Cristiana-Elena Vlad ◽  
Liliana Foia ◽  
Laura Florea ◽  
Irina-Iuliana Costache ◽  
Andreea Covic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
High Dose ◽  
The North ◽  
Increased Risk ◽  
North Eastern ◽  
North Eastern Part

Abstract Background. Familial hypercholesterolemia (FH) is one of the most frequent and important monogenic cholesterol pathology. Traditional and nontraditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease (ASCVD) in this population. Objective. To establish the prevalence and the cardiovascular risk factors of FH population, to identify the ASCVD through the clinico-biological and imaging modifications during the 24-months follow-up.Methods. This first prospective study in the north-eastern part of Romania, carried out between October 2017-October 2019, out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network (DLCN) and Simone Broome (SM) scores, only 61 patients with DLCN score above 3 and FH possible/probably (SM score) were included.Results. The 61 FH subjects recorded a mean age of 48.46±12.53 years, with more women compared to men. Regarding the traditional cardiovascular risk factors, we identified that high blood pressure was the main factor in all patients, followed by sedentary lifestyle, obesity, smoker status, personal cardiovascular history and type 2 diabetes. The measured DLCN score recorded: “possible” FH identified in 39.4%, the “probable”FH in 45.9% and the “definite” FH in 14.7%. After the administration of the lipid-lowering agents for 24 months, TC and LDL-C levels, carotid intima-media thickness (cIMT) and ankle-brachial index (ABI) decreased and HDL-C levels increased, but without reaching the guideline goals. In addition, the high-dose of statin alone, the high-dose of statin with fenofibrate, subjects with „possible” FH, the normal values of cIMT and ABI, had a reduced time of ASCVD occurrence. Also, the high cIMT values, physical inactivity, high TC, TG and high-sensitivity C-reactive protein (hsCRP) levels were associated with an increased risk of ASCVD. Conclusions. To reduce cardiovascular risk, the FH patients need a cascade screening and a specific management. Even though it was the first observational study in the north-eastern part of Romania, further molecular genetics studies are needed to confirm the FH cases.

scholarly journals Diet and Nutraceutical Supplementation in Dyslipidemic Patients: First Results of an Italian Single Center Real-World Retrospective Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2056
Author(s):  
Andrea Pasta ◽  
Elena Formisano ◽  
Anna Laura Cremonini ◽  
Elio Maganza ◽  
Erika Parodi ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Ldl Cholesterol ◽  
Plasma Lipid ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Increased Risk ◽  
First Results ◽  
Esc Guidelines ◽  
Ascvd Risk

Background: Dyslipidemias are a heterogeneous group of metabolic disorders mainly characterized by an increased risk of atherosclerotic cardiovascular disease (ASCVD) or other conditions, such as acute pancreatitis in hypertriglyceridemia. The aim of this study was to evaluate the effect of diet treatment and nutraceutical (NUTs) supplementation on the plasma lipid profile in outpatient dyslipidemic subjects, considering the influence of several factors (i.e., gender, age, body mass index, alcohol consumption, and smoking habits). Methods: 487 dyslipidemic patients spanning from 2015 to 2019 were treated with a Mediterranean diet or NUTs in a real-word setting and were retrospectively analyzed. General characteristics and lipid profile at baseline and after the follow-up period were evaluated. Results: Diet alone reduced total cholesterol (−19 mg/dL, −7.7%), LDL cholesterol (−18 mg/dL, −10.1%), and triglycerides (−20 mg/dL, −16.7%). Triglycerides (TG) decreased more in men, while women were associated with higher reduction of LDL cholesterol (LDL-C). Different types of NUTs further ameliorate lipid profiles when associated with diet. Nevertheless, most patients at low ASCVD risk (222 out of 262, 81.6%) did not achieve the 2019 ESC/EAS guidelines recommended LDL-C goals (i.e., LDL-C < 116 mg/dL). Conclusion: Lipid-lowering diet improves lipid profile, and NUTs can boost its efficacy, but taken together they are mainly unsatisfactory with respect to the targets imposed by 2019 EAS/ESC guidelines.

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