scholarly journals Correlation between different LDL-R mutations and response to ab-PCSK9 therapy in a group of patient with genetic diagnosis of Familial Hypercholesterolemia. Preliminary report

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Buonaiuto ◽  
M Gentile ◽  
I.L Calcaterra ◽  
C Giacobbe ◽  
M Tripaldella ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Secondary Prevention ◽  
Familial Hypercholesterolemia ◽  
Genetic Diagnosis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Ldlr Gene ◽  
Days Of Therapy ◽  
Significant Difference ◽  
Compound Heterozygotes

Abstract Introduction Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to premature cardiovascular disease (CAD). The availability of ab-PCSK9 has changed the approach to therapy. Purpose To evaluate the relationship between different types of mutations in LDLR gene and response to ab-PCSK9. Methods 73 FH patients, 33 women and 40 men (53.9±13. yrs), in primary prevention (N=46) and secondary prevention (N=27), were recruited. This sample included patients with mutations in LDLR gene: heterozygotes for missense mutations (N=31), for null mutations (N=31), compound heterozygotes or homozygotes (N=11). At baseline, the whole sample had a maximally tolerated lipid lowering therapy (MT-LLT) without ab-PCSK9; 16 patients had MT-LLTs intolerance. After 160 days with ab-PCSK9 therapy we evaluated the achievement of a goal (LDL-C<70 mg/dL in primary prevention without Diabetes Mellitus, LDL-C<55 mg/dL). Results After 160 days of therapy with ab-PCSK9 (45 patients on Alirocumab, 28 patients on Evolocumab) and MT-LLT, 29/73 patients (39.7%) of the whole sample achieve the goal of LDL-C. Of them 14/29 (48.2%) were in primary prevention, 15/29 (51.7%) in secondary prevention, no difference in achievement of the goal. We then evaluated the percent of patients achieving the goal of LDL-C: 15/31 (48.3%) patients with missense mutation and 14/31 (45.1%) patients with null mutation, no significant difference among groups; 0/11 compound heterozygotes or homozygotes; 3/16 (18.7%) MT-LLTs intolerance. The other main cardiovascular risk factors did not influence of the achievement the goal of LDL cholesterol. Conclusions Lack of correlation between type of mutation in heterozygous FH patients and ab-PCSK9 therapy response; response was significantly poorest in patients with compound heterozygosis or homozygosis mutation as compared to heterozygotes; the intolerance to MT-LLT was significant in the achievement of the goal of LDL-C. Different between guideline 2016 vs 2019 Funding Acknowledgement Type of funding source: None

scholarly journals ESTIMATION OF THE THICKNESS OF THE INTIMA-MEDIA COMPLEX IN CHILDREN WITH FAMILIAL HYPERCHOLESTEROLEMIA

2018 ◽  
Vol 63 (5) ◽  
pp. 152-154
Author(s):  
D. I. Sadykova ◽  
L. F. Galimova ◽  
I. V. Leontyeva ◽  
E. S. Slastnikova
Keyword(s):  
Carotid Artery ◽  
Familial Hypercholesterolemia ◽  
Common Carotid Artery ◽  
Lipid Lowering ◽  
Control Group ◽  
Lipid Lowering Therapy ◽  
Healthy Children ◽  
Early Diagnostics ◽  
Significant Difference ◽  
The Common

Objective:to evaluate the diagnostic significance of measuring the thickness of the intima-media complex (IMC) in children with autosomal dominant familial hypercholesterolemia for early diagnostics and prompt treatment of atherosclerosis.Materials and methods.The study included 109 children – 64 children with familial hypercholesterolemia and 45 healthy children. Both groups were divided into 2 subgroups according to the age – from 3 to 8 years and from 9 to 18 years. We measured the intimamedia thickness (IMT) of the common carotid artery in all the children. To evaluate IMT we used an ultrasound scanner HD11XE (Philips, USA) with a linear (3–12MHz) sensor IMT.Results.We found a statistically significant difference (p=0.012) of the IMT of the common carotid artery in children with familial hypercholesterolemia (0.61 ± 0.02 mm) in comparison with the control group (0.49±0.02 mm), starting from the age of 9 years. There were no sex differences of IMT in patients older than 9 years.Conclusion.We found that children with familial hypercholesterolemia have higher values of IMT already from the age of 9 as compared with healthy children; the increase in TCIM is an additional criterion for the early diagnostics of atherosclerosis and evaluation of cardiovascular risk. These results emphasize the relevance of lipid-lowering therapy for patients with familial hypercholesterolemia in childhood, before the first signs of atherosclerosis appear.

Abstract 15576: Cardiovascular Disease in Elderly Familial Hypercholesterolemia Individuals Attending a Cascade Screening Program

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
elaine coutinho ◽  
Marcio H Miname ◽  
Viviane Z Rocha ◽  
Marcio S Bittencourt ◽  
Cinthia Jannes ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolemia ◽  
High Intensity ◽  
Screening Program ◽  
Coronary Revascularization ◽  
Genetic Diagnosis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cvd Risk ◽  
Cascade Screening

Introduction: Familial hypercholesterolemia (FH) is associated with early onset of cardiovascular disease (CVD) and mortality. Lipid lowering treatment (LLT) may change the natural history of FH, however there is scant information about elderly individuals (older than 60 years) with FH. This study describes characteristics of elderly FH individuals presenting or not CVD. Hypothesis: Monogenic defects are important markers of CVD risk and initiation and long-term use of lipid lowering therapy (LLT) is relevant to minimize this risk. Methods: Cross-sectional analysis of clinical and laboratory of molecularly proven elderly FH (FH+) and non-affected (FH-) individuals attending a cascade screening program. FH+ were divided in those presenting or not CVD (defined as previous myocardial infarction or ischemic stroke, carotid or coronary revascularization and angina with stenosis ≥50% on angiography). Results: From 4,111 genotyped individuals, 462 (11.2%) elders were included (198 FH+ and 264 FH-). There was predominance of females in either groups, however with more men in FH+ 37.4% vs. 24.2%, p=0.002. No differences were seen between FH+ and FH- regarding age, [median (%25;75%)] 66 (62;71) and 66 (63;71) years, p=0.68; use of LLT 88.5% vs. 91.5%, p=0.29 and high intensity LLT 61.7 % vs. 55.8%, p=0.20, respectively. Despite longer LLT duration in FH+ 11(7;20) vs. 7 (3;13) years, p<0.001, in either groups LLT was started late, at 54 (47;61) and 59 (52;64) years, p <0.001, respectively in FH+ and FH-. FH+ had higher LDL-C at diagnosis, 243 (179;302) vs. 228 (209;251) mg/dL, p=0.013, as well as greater frequencies of previous CVD 40.9% vs. 27.3%, p=0.002, and early CVD 22.2% vs. 9.0%, p<0.001. In FH+, male sex [OR (95%CI)] 5.29 (2.25-12.45), p<0.001, and use of high intensity LLT 2.51 (1.08-5.87), p=0.03, were independently associated with CVD. Conclusions: The genetic diagnosis of FH was associated with higher rates of CVD and early CVD vs. FH- hypercholesterolemics. Elders with FH+ who survived despite late LLT initiation have a worse CVD history than FH- elders, emphasizing the relevance of a monogenic defect as cause of long-lasting hypercholesterolemia and CVD risk, particularly in men.

scholarly journals Lipid-Lowering Agents in Older Individuals: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

2019 ◽  
Vol 104 (5) ◽  
pp. 1585-1594 ◽  
Author(s):  
Oscar J Ponce ◽  
Laura Larrea-Mantilla ◽  
Bianca Hemmingsen ◽  
Valentina Serrano ◽  
Rene Rodriguez-Gutierrez ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Secondary Prevention ◽  
Cardiovascular Mortality ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Older Individuals ◽  
Diabetes Status ◽  
Significant Difference ◽  
Lipid Lowering Agents

Abstract Background The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. Methods We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. Pairs of reviewers selected and appraised the trials. Results We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

scholarly journals Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy

2019 ◽  
Vol 8 (12) ◽  
pp. 2209 ◽  
Author(s):  
Victoria Marco-Benedí ◽  
Martin Laclaustra ◽  
Juan M. Casado-Dominguez ◽  
Rosa Villa-Pobo ◽  
Rocío Mateo-Gallego ◽  
...  
Keyword(s):  
Risk Factors ◽  
Aortic Valve ◽  
Familial Hypercholesterolemia ◽  
Genetic Diagnosis ◽  
Statin Treatment ◽  
Valvular Disease ◽  
Lipid Lowering ◽  
Elderly Subjects ◽  
Lipid Lowering Therapy ◽  
Aortic Sclerosis

Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ≥65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl, and statin treatment ≥5 years. Controls were relatives of HeFH patients, with LDLc <190 mg/dl. Participants underwent a cardiac ultrasound for aortic valve analysis. We studied 205 subjects, 112 HeFH and 93 controls, with mean age 71.8(6.5) years and 70.0(7.3) years, respectively. HeHF, with respect to controls, presented greater gradients of aortic transvalvular pressure, 7.4(7.3) mmHg versus 5.0(2.8) mmHg, and maximum aortic velocity, 1.7(0.7) m/s versus 1.5(0.4) m/s, and lower aortic valve opening area, 2.0(0.7) cm2 versus 2.4(0.6) cm2 (all p < 0.05). AoVC and ASc were also more prevalent in HeFH (p < 0.05 between groups). Moderate/severe AS prevalence was higher among HeFH: 7.1% versus 1.1% (age- and sex-adjusted odds ratio (OR) 8.33, p = 0.03). Independent risk factors for aortic valve disease in HeFH were age and LDLc before treatment. The number of years under statin treatment was not associated with any aortic valve measurement. Subjects ≥65 years with HeFH in prolonged statin treatment show more aortic valvular disease and higher frequency of AS than controls. Life-long elevated LDLc exposure, rather than time of exposure to statins, explains this higher risk.

Abstract 3699: Efficacy and Safety of Colesevelam HCl in Pediatric Patients with Heterozygous Familial Hypercholesterolemia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Evan A Stein ◽  
David Marais ◽  
Tamas Szamosi ◽  
Frederick Raal ◽  
Daniel Schurr ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Degree Relative ◽  
Double Blind ◽  
Heterozygous Familial Hypercholesterolemia

Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder resulting in elevated LDL-C, which confers a high risk for a coronary event. Colesevelam HCl (COL), a non-absorbable bile acid sequestrant, is approved to lower LDL-C in adults with primary hypercholesterolemia. This is the first data demonstrating the efficacy and safety of COL in pediatric pts with heFH. This 32wk multicenter, randomized, double-blind (DB), placebo (PLA)-controlled study included: a 4wk PLA run-in (to measure compliance); an 8wk DB period (pts randomized 1:1:1 to PLA, 1.875 g/d COL, or 3.75 g/d COL); an 18wk open-label (OL) treatment to goal (LDL-C <110 mg/dL) wherein all pts received COL 3.75 g/d (and were eligible to receive a statin); and a 2wk follow-up. Males and females, aged 10 –17yrs, with either genetic diagnosis of heFH or history of untreated LDL-C >160 mg/dL combined with familial dyslipidemia in a first degree relative, who had a baseline LDL-C >160 mg/dL (if naíve to lipid-lowering therapy) or >130 mg/dL (if on a statin [≥6wks]) and following a NCEP step 1 diet were included. Additional inclusion criteria were TG <250 mg/dL, ≥Tanner stage 2, and compliance ≥75% during the PLA run-in. Primary efficacy parameter was % change in LDL-C from baseline/Day 1 to Wk 8. The ITT population (randomized pts with a baseline and ≥1 post-baseline measurement) was used to evaluate efficacy parameters. Of the 194 pts randomized, 95.9% and 89.2% completed the DB and OL periods, respectively. Approximately 25% were on a statin at entry into the DB period; a further 10% added a statin during the OL period. At wk 8, LDL-C, TC, and apoB significantly decreased while HDL-C and apoA-I significantly increased with COL 3.75 g/d ( P <0.01 vs PLA for all; Table ). Adverse events were as expected; no choking was recorded. No effects were noted on growth, sexual maturation, hormone levels, absorption of fat-soluble vitamins, or clotting parameters. In summary, COL lowered LDL-C and was well tolerated in pediatric pts.

Standard and intensive lipid-lowering therapy with statins for the primary prevention of vascular diseases: a population-based study

2013 ◽  
Vol 70 (1) ◽  
pp. 99-108 ◽  
Author(s):  
D. Macías Saint-Gerons ◽  
C. de la Fuente Honrubia ◽  
D. Montero Corominas ◽  
M. J. Gil ◽  
F. de Andrés-Trelles ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Vascular Diseases ◽  
Population Based ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Population Based Study ◽  
Lowering Therapy

Evaluation on the compliance with secondary prevention and influence factors of ischemic stroke in Hainan province, China

Vascular ◽  
2013 ◽  
Vol 22 (3) ◽  
pp. 181-187 ◽  
Author(s):  
Qingjie Su ◽  
Kunxiong Yuan ◽  
Faqing Long ◽  
Zhongqin Wan ◽  
Chaoyun Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Health Education ◽  
Secondary Prevention ◽  
Antiplatelet Therapy ◽  
Influence Factors ◽  
Significant Risk ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Logistic Regression Models ◽  
Prevention Therapy

Survivors of ischemic stroke are still at a significant risk for recurrence. Numerous effective strategies for the secondary prevention of ischemic stroke have now been established; however, these guidelines are not widely known. In this retrospective, a multicenter study was conducted from January 2011 to February 2012 in 10 general hospitals, which included 1300 elderly patients who had previously been diagnosed with ischemic stroke and re-admitted to hospitals. Logistic regression models were fitted to determine the relationship between compliance with secondary prevention therapy and each variable of interest. The treatment rates of antihypertensive, antiplatelet and lipid-lowering therapy were only 56.3%, 48.9% and 19.6%, respectively. Multivariate analysis presented that cardiovascular risk factors would motivate patients with hypertension and hyperlipidemia to receive corresponding treatments. However, it is worth noting that they did not influence the use of antiplatelet therapy. In addition, high education, health education and insurance promote the use of secondary prevention in patients. In conclusion, the importance of antiplatelet therapy should not be ignored any more. Besides, health education will raise patients’ attention to ischemic stroke.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

2019 ◽  
Vol 12 (9) ◽  
pp. 1797-1804 ◽  
Author(s):  
Marcio H. Miname ◽  
Marcio Sommer Bittencourt ◽  
Sérgio R. Moraes ◽  
Rômulo I.M. Alves ◽  
Pamela R.S. Silva ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Coronary Artery Calcium ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

scholarly journals Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e020309 ◽  
Author(s):  
Sofia Axia Karlsson ◽  
Christel Hero ◽  
Ann-Marie Svensson ◽  
Stefan Franzén ◽  
Mervete Miftaraj ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Primary Prevention ◽  
Secondary Prevention ◽  
Exposure Period ◽  
Lipid Lowering ◽  
Refill Adherence

ObjectivesTo analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus.DesignCohort study.SettingNational population-based cohort of Swedish patients with type 2 diabetes mellitus.Participants86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007–2010, 87% for primary prevention.Exposure and outcome measuresRefill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%–40%, 41%–60%, 61%–80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics.ResultsThe hazard ratios for CVD ranged 1.33–2.36 in primary prevention patients and 1.19–1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001).ConclusionsHigher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.

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