scholarly journals Analysis of Arterial Stiffness and Sexual Function after Adding on PCSK9 Inhibitor Treatment in Male Patients with Familial Hypercholesterolemia: A Single Lipid Center Real-World Experience

2020 ◽  
Vol 9 (11) ◽  
pp. 3597
Author(s):  
Roberto Scicali ◽  
Giorgio Ivan Russo ◽  
Marina Di Mauro ◽  
Flavia Manuele ◽  
Grazia Di Marco ◽  
...  
Keyword(s):  
Sexual Function ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
P Value ◽  
Pcsk9 Inhibitor ◽  
Male Patients ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Male Subjects ◽  
Inhibitor Treatment

Familial hypercholesterolemia (FH) subjects have high low-density lipoprotein cholesterol (LDL-C) and may be at high risk of erectile dysfunction and atherosclerotic cardiovascular diseases. We evaluated the effect of PCSK9-i on sexual function evaluated by the Male Sexual Health Questionnaire (MSHQ) and the International Index of Erectile Function (IIEF-5) questionnaire and on pulse wave velocity (PWV) in FH male subjects. In this prospective observational study, we evaluated 30 FH male patients on high-intensity statins plus ezetimibe and with an LDL-C off-target. All patients added PCSK9-i treatment and obtained clinical assessment at baseline and after six months of PCSK9-i. As expected, LDL-C significantly decreased after adding-on PCSK9-i (−48.73%, p < 0.001). MSHQ and PWV significantly improved after adding-on PCSK9-i (for MSHQ 93.63 ± 6.28 vs. 105.41 ± 5.86, p < 0.05; for PWV 9.86 ± 1.51 vs. 7.7 ± 1.42, p < 0.05); no significant change of IIEF-5 was found. Finally, a simple regression showed that ∆ MSHQ was significantly associated with ∆ LDL-C and ∆ PWV (p value for both <0.05). In conclusion, PCSK9-i therapy significantly improves lipid profile, PWV, and sexual function in FH male patients; our results support the favorable function of PCSK9-i on these parameters.

scholarly journals Incidence of Cardiovascular Disease in Patients with Familial Hypercholesterolemia Phenotype: Analysis of 5 Years Follow-Up of Real-World Data from More than 1.5 Million Patients

2019 ◽  
Vol 8 (7) ◽  
pp. 1080 ◽  
Author(s):  
Luís Masana ◽  
Alberto Zamora ◽  
Núria Plana ◽  
Marc Comas-Cufí ◽  
Maria Garcia-Gil ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Primary Care System ◽  
Low Density Lipoprotein Cholesterol ◽  
Real World Data ◽  
Old Patients ◽  
Phenotype Analysis ◽  
Atherosclerotic Cardiovascular Diseases

In the statin era, the incidence of atherosclerotic cardiovascular diseases (ASCVD) in patients with familial hypercholesterolemia (FH) has not been updated. We aimed to determine the incidence of ASCVD in patients with FH-phenotype (FH-P) and to compare it with that of normal low-density lipoprotein cholesterol (LDL-C) patients. We performed a retrospective cohort study using the Database of the Catalan primary care system, including ≥18-year-old patients with an LDL-C measurement. From 1,589,264 patients available before 2009, 12,823 fulfilled FH-P criteria and 514,176 patients were normolipidemic (LDL-C < 115 mg/dL). In primary prevention, patients with FH-P had incidences of ASCVD and coronary heart disease (CHD) of 14.9/1000 and 5.8/1000 person-years, respectively, compared to 7.1/1000 and 2.1/1000 person-years in the normolipidemic group. FH-P showed hazard ratio (HR) of 7.1 and 16.7 for ASCVD and CHD, respectively, in patients younger than 35 years. In secondary prevention, patients with FH-P had incidences of ASCVD and CHD of 89.7/1000 and 34.5/1000 person-years, respectively, compared to 90.9/1000 and 28.2/1000 person-years in the normolipidemic group (HR in patients younger than 35 years: 2.4 and 6.0). In the statin era, FH-P remains associated with high cardiovascular risk, compared with the normolipidemic population. This excess of risk is markedly high in young individuals.

scholarly journals PCSK9 Inhibitors in a Statin-Intolerant Transgender Man With Heterozygous Familial Hypercholesterolemia: A Case Report

2019 ◽  
Vol 3 (8) ◽  
pp. 1461-1464 ◽  
Author(s):  
Carlo Pirazzi ◽  
Federica Tavaglione ◽  
Åsa Tivesten ◽  
Stefano Romeo
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Genetic Diagnosis ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Lipid Clinic ◽  
High Doses

Abstract In female-to-male transgender individuals, testosterone is used to induce masculinization. Sex steroid therapy may increase circulating triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and may decrease high-density lipoprotein cholesterol (HDL-C) levels, resulting in a more atherogenic lipid profile. These potentially adverse effects of androgen therapy may be exacerbated by the presence of familial hypercholesterolemia (FH). We describe the case of a transgender man with genetically diagnosed FH who was intolerant to statins and was started on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to control his lipoproteins more effectively. The 35-year-old female-to-male transgender individual was referred to our center with a history of elevated LDL-C levels. Despite treatment with high doses of high-potency statins and ezetimibe, he had never achieved a sustained reduction in LDL-C; his levels of LDL-C were fluctuating between 170 and 344 mg/dL (4.4 and 8.9 mmol/L). Moreover, he developed side effects to statins in the form of myalgia and discontinued statin treatment. At the Sahlgrenska Lipid Clinic, a genetic diagnosis of heterozygous FH was established, and PCSK9 inhibitor therapy was started. The patient’s LDL-C level has been reduced by approximately 40% for 23 months, and no adverse events have been reported.

scholarly journals The Prevalence of Heterozygous Familial Hypercholesterolemia in Selected Regions of the Russian Federation: The FH-ESSE-RF Study

2021 ◽  
Vol 11 (6) ◽  
pp. 464
Author(s):  
Alexey N. Meshkov ◽  
Alexandra I. Ershova ◽  
Anna V. Kiseleva ◽  
Svetlana A. Shalnova ◽  
Oxana M. Drapkina ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Russian Federation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitor ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic ◽  
The Russian Federation ◽  
Artery Disease

Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic conditions but remains substantially underdiagnosed. The aim of our study was to investigate the prevalence of HeFH in the population of 11 different regions of Russia. Individuals were selected from the Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study. All participants who had low-density lipoprotein cholesterol (LDL-C) higher than 4.9 mmol/L, or LDL-C lower than 4.9 mmol/L, but had statin therapy, were additionally examined by FH experts. FH was diagnosed using the Dutch Lipid Clinic Network criteria, incorporating genetic testing. HeFH prevalence was assessed for 18,142 participants. The prevalence of patients with definite or probable HeFH combined was 0.58% (1 in 173). A total of 16.1% of patients with definite or probable HeFH had tendon xanthomas; 36.2% had mutations in one of the three genes; 45.6% of FH patients had coronary artery disease; 63% of HeFH patients received statins; one patient received an additional PCSK9 inhibitor; no patients received ezetimibe. Only 3% of patients reached the LDL-C goal based on 2019 ESC/EAS guidelines. Underdiagnosis and undertreatment of FH in Russia underline the need for the intensification of FH detection with early and aggressive cholesterol-lowering treatment.

scholarly journals The LDLR c.501C>A is a disease-causing variant in familial hypercholesterolemia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Haochang Hu ◽  
Ruoyu Chen ◽  
Yingchu Hu ◽  
Jian Wang ◽  
Shaoyi Lin ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Lipid Level ◽  
Density Lipoprotein ◽  
Hek293 Cells ◽  
Lipid Lowering ◽  
Therapeutic Effects ◽  
Autosomal Dominant Disorder ◽  
Pcsk9 Inhibitor ◽  
Inhibitor Treatment

Abstract Background As an autosomal dominant disorder, familial hypercholesterolemia (FH) is mainly attributed to disease-causing variants in the low-density lipoprotein receptor (LDLR) gene. The aim of this study was to explore the molecular mechanism of LDLR c.501C>A variant in FH and assess the efficacy of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor treatment for FH patients. Methods The whole-exome sequencing was performed on two families to identify disease-causing variants, which were verified by Sanger sequencing. The function of LDLR variant was further explored in HEK293 cells by Western Blot and confocal microscopy. Besides, the therapeutic effects of PCSK9 inhibitor treatment for two probands were assessed for 3 months. Results All members of the two families with the LDLR c.501C>A variant showed high levels of LDLC. The relationship between the clinical phenotype and LDLR variants was confirmed in the current study. Both in silico and in vitro analyses showed that LDLR c.501C>A variant decreased LDLR expression and LDL uptake. PCSK9 inhibitor treatment lowered the lipid level in proband 1 by 24.91%. However, the treatment was ineffective for proband 2. A follow-up study revealed that the PCSK9 inhibitor treatment had low ability of lipid-lowering effect in the patients. Conclusions LDLR c.501C>A variant might be pathogenic for FH. The PCSK9 inhibitor therapy is not a highly effective option for treatment of FH patients with LDLR c.501C>A variant.

Comparison of sexual function changes in recipients of kidney transplant in females receiving kidney from the living donor and deceased donor

2020 ◽  
Vol 87 (4) ◽  
pp. 203-208
Author(s):  
Mohammadreza Nikoobakht ◽  
Negar Behtash ◽  
Mahdi Ramezani-Binabaj ◽  
Erfan Jelveh-Moghaddam ◽  
Alimohammad Fakhr Yasseri ◽  
...  
Keyword(s):  
Sexual Function ◽  
Kidney Transplant ◽  
Living Donor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Deceased Donor ◽  
Female Sexual Function Index ◽  
P Value ◽  
Female Sexual Function ◽  
Function Index

Background and Aim: Chronic renal failure can result in different sexual and reproductive problems for women. Due to lack of information about sexual dysfunction of women with transplanted kidney and superiority of either living or deceased donor, we designed this retrospective cohort study to compare sexual function changes in recipients of kidney transplant in two groups receiving kidney from the living donor and deceased donor using Female Sexual Function Index score. Methods and Materials: We included 55 female patients who underwent kidney transplant from 22 May 2015 to 22 May 2016 in Sina Hospital (Tehran, Iran). Laboratory factors, including creatinine, blood urea nitrogen, hemoglobin, fasting blood glucose, triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein, were evaluated before and after the transplantation. Female Sexual Function Index questionnaire was used to evaluate sexual function of the patients before the transplant, 3 months after the transplant, and 9 months after the transplant. Results: Our results revealed that there is significant improvement in the Female Sexual Function Index score of the patients after the transplant (p-value < .001). However, we found no significant difference between the scores of the patients with living donor and deceased donor (p-value > .05). Patients’ age, creatinine level, low-density lipoprotein, and diastolic blood pressure are negative predictors of Female Sexual Function Index scores.

scholarly journals Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies

2020 ◽  
pp. 204748732091580 ◽  
Author(s):  
Tahir Mahmood ◽  
Jessica Minnier ◽  
Matthew K Ito ◽  
Qian H Li ◽  
Andrew Koren ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Pooled Analysis ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Phase 3 ◽  
Pcsk9 Inhibitor

Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50–60% and lipoprotein(a) (Lp(a)) by 20–30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab. Methods This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%. Results Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance. Conclusion A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.

Gefäßdarstellung mit 131I-low-density Lipoprotein bei Patienten mit Hypertonie und frühen atherosklerotischen Läsionen der Arteria carotis

VASA ◽  
1999 ◽  
Vol 28 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Lupattelli ◽  
Siepi ◽  
Palumbo ◽  
Fedeli ◽  
Ciuffetti ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Low Density ◽  
Atherosclerotic Lesions ◽  
Uptake Pattern ◽  
Lipoprotein Uptake ◽  
Lipid Pattern ◽  
Male Patients ◽  
Male Subjects

Background: The reinjection of autologous 131I-labelled low-density lipoprotein (LDL) followed by vascular scintigraphy has been used to investigate lipid-containing plaques, but no information is available on the early stages of plaques in hypertensives. Vascular scintigraphy after re-injection of autologous 131I-labelled LDL was used to investigate early atherosclerotic lesions visualized by sonography in the carotid arteries of patients with hypertension. Patients and methods: 10 male patients (4 smokers; mean age 56 ± 8 years;) with early carotid atherosclerosis (mono- or bilateral; intima-media-thickness ranging from 1.5 to 3.5mm) as shown by sonography were studied. All these normolipemic patients suffered from primary hypertension and were treated with diuretics. As controls 6 healthy male subjects (3 smokers; mean age 54 ± 9 years;), with normal blood pressure and lipid pattern were recruited. Results: Hot spots appeared in the areas with early atherosclerosis in 7 patients, while none were seen in controls. Positive kinetic curves were observed in 4 patients. No significant differences emerged in the target/non-target ratios. Conclusions: Vascular lipoprotein uptake in hypertensive patients is apparently late and rather limited; the uptake pattern may depend on plaque composition.

scholarly journals Use of PCSK9 Inhibitor in a Mexican Boy with Compound Heterozygous Familial Hypercholesterolemia: A Case Report

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
José Juan Ceballos-Macías ◽  
Ramón Madriz-Prado ◽  
Norma Alejandra Vázquez Cárdenas ◽  
Carlos Aguilar-Salinas ◽  
Maria Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Compound Heterozygous ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Functional Studies ◽  
Dietary Plan

Abstract We report on the case of an 8-year-old Mexican male, with a 3-year-old clinical diagnosis of familial hypercholesterolemia, and the difficulties encountered in his treatment while in our care. His treatment started with a regimen consisting of ezetimibe/simvastatin, cholestyramine, and a dietary plan of 1600 calories, with a limited intake of 200 mg of cholesterol per day. Problems arose when the patient’s low-density lipoprotein cholesterol (LDL) levels did not meet ideal targets, which prompted the use of LDL cholesterol apheresis (not available in Mexico) for 6 months. As a last resort, PCSK9 inhibitors were administered but the LDL levels remained in the 600 mg/dL range. AmbryGenetics conducted a genetic test employing the Sanger method. The results suggested that there were 2 different mutations for each allele of the same LDL receptor gene (c.249delTinsGG and p.(Cys109Arg)), located in exons 3 and 4, respectively. We identified compound heterozygous mutations in our index case, with him having both the p.C109R mutation (from the maternal lineage), as well as a c.249delTinsGG mutation (from the paternal lineage). The p.C109R mutation has been previously reported, not only in Mexico, but in European regions (Germany, Czech Republic, Ireland, Italy) as well. Functional studies indicated a residual enzymatic activity of 15% to 30% for heterozygotes. To date, the variant c.249delTinsGG has not been reported. This case study illustrates the fact that in Mexico there are limited options available for treatment in such a scenario. As medical professionals, we are limited by the tools at our disposal.

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