scholarly journals Current Causes of Death in Familial Hypercholesterolemia

2021 ◽  
Author(s):  
Victoria Marco Benedí ◽  
Ana M Bea ◽  
Ana Cenarro ◽  
Estíbaliz Jarauta ◽  
Martín Laclaustra ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Causes Of Death ◽  
Low Density Lipoprotein ◽  
Family Members ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Cvd Risk ◽  
Premature Cardiovascular Disease ◽  
And Control ◽  
Cvd Mortality

Abstract Background: Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined and effective lipid-lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heFH. Methods: Case-control study designed to analyze life-long mortality in a group of heFH and control families. Data of first-degree family members of cases and controls (non-consanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH, non-heFH, and non-consanguineous family members.Results: We analyzed 813 family members, 26.4% of them, deceased. Among deceased, mean age of death was 69.3 years in heFH, 73.5 years in non-heFH, and 73.2 years in non-consanguineous, differences that were not statistically significant. Among them, CVD cause of death was 59.7% in heFH, 37.7.% in non-heFH, and 37.4% in non-consanguineous (P=0.012). These differences were greater restricting the analyses to parents’ mortality. The hazard ratio of dying from CVD was 3.02 times higher (95% CI, 1.90-4.79) in heFH members in comparison with the other two groups (non-FH and non-consanguineous), who did not differ in their risk.Conclusions: Current CVD mortality in heFH is lower and occurs later than that described in the last century but still higher than in non-FH. This better prognosis in CVD risk is not associated with changes in non-CVD mortality.

scholarly journals Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata
Keyword(s):  
Monoclonal Antibodies ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Genetic Defect ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Premature Cardiovascular Disease

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.

scholarly journals Homozygous familial hypercholesterolemia with an update on cholesterol management

2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Anju J J Velvet ◽  
Handrean Soran ◽  
Bernard Clarke ◽  
Manish Motwani ◽  
Farzin F Ordoubadi ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Microsomal Triglyceride Transfer Protein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Management Options ◽  
Lipid Management ◽  
Premature Cardiovascular Disease ◽  
Density Lipoprotein Receptor

ABSTRACT Familial hypercholesterolemia (FH) is an autosomal dominant condition that increases the risk of premature cardiovascular disease. Despite advances in treatment, it remains under detected and under treated. As an inherited condition, it poses a risk to the patient and family members. Most cases are due to defective low-density lipoprotein receptor (LDLR) activity. Heterozygous mutations are common (1:250–1:300). Homozygous FH is very rare (2–3 in a million), with higher circulating cholesterol levels and a poorer cardiovascular prognosis. We present the management of a case of homozygous hypercholesterolemia due to homozygous LDLR mutation. The patient subsequently developed severe coronary artery and aortic valve disease despite aggressive lipid-lowering therapy. We review advanced lipid management options that include lipoprotein apheresis, Proprotein Convertase Subtilisin/Kexin type 9 inhibition, and the microsomal triglyceride transfer protein inhibitor lomitapide.

scholarly journals Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?

2018 ◽  
Vol 12 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Andromachi Reklou ◽  
Michael Doumas ◽  
Konstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Dimitris Patoulias ◽  
...  
Keyword(s):  
Vascular Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Lipid Lowering ◽  
Human Antibody ◽  
Low Grade ◽  
Cvd Risk ◽  
Expensive Drug ◽  
Arterial Inflammation

Background: Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD). Objective: In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events. Results: In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels. Conclusion: Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.

Abstract 406: Achievement of Treatment Target in Korean Patients With Familial Hypercholesterolemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chan Joo Lee ◽  
Jaewon Oh ◽  
Jung Sun Kim ◽  
Sang-Hak Lee
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Treatment Target ◽  
Evaluation Point ◽  
The Mean ◽  
Artery Disease ◽  
Primary Evaluation

Background: In many cases of familial hypercholesterolemia (FH), there remains difficulty in achievement of treatment target. However, despite growing attention to FH, data on the treatment and its results in these patients are very limited. Methods: From nine sites in Korea, 122 consecutive unrelated men and women who were diagnosed with heterozygous FH by Simon Broome criteria were initially enrolled. Atorvastatin 20 mg or similar-potency drugs were prescribed and the dose was escalated every 2 months (for the first 6 months) or 6 months (thereafter) if needed. Forty one subjects were dropped and 81 subjects who underwent regular laboratory check-up were finally analyzed. The primary evaluation points were achievement rates of low-density lipoprotein cholesterol (LDL-C) <70 mg/dL, LDL-C<100 mg/dL, and LDL-C down to 50% of baseline levels at 12 month. The secondary evaluation point was % change of LDL-C at 12 month. Results: Patients’ mean age was 53 years and 59.3% were males. 21.0% were definite type FH and 28.4% had coronary artery disease (CAD). The mean total cholesterol and LDL-C were 319 mg/dL and 232 mg/dL, respectively. At 12 month, 7.4% received atorvastatin 10mg or similar, 21.0% received atorvastatin 20mg or similar, 16.0% received atorvastatin 40mg or similar, 4.9% received atorvastatin 80mg or similar, and 49.4% received atorvastatin (mean 57 mg) or similar plus ezetimibe 10mg. The mean follow-up total cholesterol and LDL-C were 201 mg/dL and 124 mg/dL, respectively. The mean % change of LDL-C was -45.6%. The achievement rates of LDL-C<70 mg/dL, <100 mg/dL, and LDL-C down to 50% of baseline were 1%, 21%, and 44%, respectively. The achievement rates were not significantly different between the patients without or with CAD (1.8%, 26.3%, 47.4% vs. 0%, 8.7%, 34.8%, respectively, all p values > 0.05). Conclusions: The achievement rate of treatment target in FH was low in Korea even after maximum tolerable dose of lipid lowering drugs. Improvement of awareness on this issue and more aggressive treatment are needed for this population.

scholarly journals Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China

Circulation ◽  
2020 ◽  
Vol 141 (7) ◽  
pp. 530-539 ◽  
Author(s):  
Shijun Xia ◽  
Xin Du ◽  
Lizhu Guo ◽  
Jing Du ◽  
Clare Arnott ◽  
...  
Keyword(s):  
Sex Differences ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Education Level ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Primary And Secondary Prevention ◽  
Cvd Risk ◽  
Cvd Prevention

Background: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. Methods: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. Results: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)–lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65–0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56–0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45–0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52–0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14–1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57–0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24–17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61–2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38–0.55]; OR, 0.60 [95% CI, 0.52–0.69]; OR, 0.55 [95% CI, 0.48–0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01–1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. Conclusions: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.

scholarly journals Non-HDL Cholesterol Versus LDL Cholesterol as a CVD Risk Factor in Diabetic Subjects

2014 ◽  
Vol 31 (4) ◽  
pp. 199-203
Author(s):  
M Saiedullah ◽  
S Begum ◽  
S Hayat ◽  
SM Kamahuddin ◽  
MR Rahman ◽  
...  
Keyword(s):  
Risk Factor ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Upward Trend ◽  
Cvd Risk ◽  
Cross Sectional

Objective: Serum low density lipoprotein (LDL) cholesterol is considered as the primary target of lipid lowering therapy and non-high density lipoprotein (HDL) cholesterol is the recommended second target. Recent studies claimed that non-HDL cholesterol is a better predictor of cardiovascular diseases (CVD) than LDL cholesterol. In this study we aimed to compare non-HDL cholesterol and LDL cholesterol as a CVD risk factor in confirmed diabetic subjects. Materials and methods: In this cross-sectional observational study, 1042 confirmed diabetic subjects selected randomly were included. HbA1cResults: In the total subjects, 767 (74%) subjects had LDL cholesterol > 100 mg/dL and 822 (79%) subjects had non- HDL cholesterol > 130 mg/dL. HbA1c values were different (p<0.02) in five groups and showed upward trend (p<0.01). All the lipid parameters studied were significantly different in five groups (p<0.0001) and TC, TG and non-HDL cholesterol showed upward trend (p<0.0001), but HDL cholesterol and LDL cholesterol showed downward trend (p<0.0001). Odds ratio (OR) of likelihood of risk individuals regarding non-HDL cholesterol compared to LDL cholesterol were 0.50 (p<0.001), 1.32 (p>0.05), 2.96 (p<0.001), 6.49 (p<0.001) and 9.37 (p<0.001) for TG concentrations of up to 150 mg/dL, 151-200 mg/dL, 201-250 mg/dL, 251-300 mg/dL and 301-400 mg/dL respectively with relative risk of 0.60, 1.24, 2.43, 4.83, 5.10. Conclusion: LDL cholesterol is a better tool for the detection of high-risk individuals than non-HDL cholesterol at TG concentration up to 150 mg/dL, whereas non-HDL cholesterol is better than LDL cholesterol at TG concentration above 200 mg/dL as a CVD risk factor. DOI: http://dx.doi.org/10.3329/jbcps.v31i4.21004 J Bangladesh Coll Phys Surg 2013; 31: 199-203

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study

2020 ◽  
Vol 26 (1) ◽  
pp. 51-58
Author(s):  
Vana Kolovou ◽  
Niki Katsiki ◽  
Stamatis Makrygiannis ◽  
Sophie Mavrogieni ◽  
Nikoletta Karampetsou ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein Apheresis ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Previously Treated

Aim: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). Patients and Methods: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. Results: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively ( P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively ( P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. Conclusions: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.

Abstract 14270: The Effect of Evinacumab on Apheresis Eligibility in Patients With Homozygous Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Frederick J Raal ◽  
Robert S Rosenson ◽  
Laurens F Reeskamp ◽  
G. Kees Hovingh ◽  
John J Kastelein ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Human Monoclonal Antibody ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Homozygous Familial Hypercholesterolemia ◽  
Double Blind ◽  
Lipid Disorder ◽  
Artery Disease

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C >160 mg/dL [primary prevention] or >120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.

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