scholarly journals GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyoeun Kim ◽  
Chan Joo Lee ◽  
Hayeon Pak ◽  
Doo-Il Kim ◽  
Moo-Yong Rhee ◽  
...  

Abstract Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiao Gong ◽  
Yaqiong Chen ◽  
Yusheng Jie ◽  
Mingkai Tan ◽  
Zhaofang Jiang ◽  
...  

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.


Author(s):  
Suzanne V. Arnold ◽  
Christopher P. Cannon ◽  
James A. de Lemos ◽  
Robert S. Rosenson ◽  
Christie M. Ballantyne ◽  
...  

Background Because of an increasing number and complexity of treatment options for lipid‐lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision‐making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid‐lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low‐density lipoprotein cholesterol (LDL‐C) control (LDL‐C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low‐Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid‐lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL‐C level, and 69% did not know their LDL‐C goal. Patients on PCSK9 inhibitors (versus LDL‐C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient‐reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid‐lowering medications, current LDL‐C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision‐making and treatment adherence. Registration URL: https://www.clinicaltrials.org ; Unique identifier: NCT02993120.


Author(s):  
Karl J. Krobot ◽  
Donald D. Yin ◽  
Evo Alemao ◽  
Elisabeth Steinhagen-Thiessen

Background Determinants of the real-world effectiveness of lipid-lowering therapy have been rarely assessed in an unselected observational coronary heart disease (CHD) community cohort over time. Design Randomly drawn patients (n = 605) from randomly drawn practices (n = 62) were retrospectively followed for a median of 3.6 years (1998-2002) on lipid-lowering therapy (98% statins). Methods Coronary heart disease population-averaged estimates and variances accounting for repeated measurements within patients were obtained using generalized estimating equations. Results Post-treatment low-density lipoprotein-cholesterol (LDL-C) was 124 mg/dl in men and 141 mg/dl in women and was independently associated (all P<0.05) with pre-treatment LDL-C (+ 3.7 mg/dl per 10 mg/dl increment), female sex (+ 14.0 mg/dl), coronary bypass (-9.5 mg/dl), drug-treated diabetes mellitus (-6.8 mg/dl), and era 2002/2001 versus 1999/2000 (- 6.4 mg/dl) in age-adjusted multivariate analyses. Holding pre-treatment LDL-C constant post-treatment LDL-C was associated with pre-treatment Framingham CHD risk in men (- 13.9 mg/dl per doubling of risk), whereas LDL-C control in women resembled that in low-risk men. The likelihood of attaining LDL-C < 100 mg/dl was 0.28 in men and 0.17 in women and was likewise associated with the above factors. Conclusion Low-density lipoprotein-cholesterol control remained low despite lipid-lowering therapy across a wide range of pre-treatment LDL-C and pre-treatment CHD risk. Low-density lipoprotein-cholesterol control in women was inferior to that in men, a finding that warrants attention and clarification. Eur J Cardiovasc Prev Rehabil 12:37-45 © 2005 The European Society of Cardiology


2020 ◽  
Vol 16 (1) ◽  
pp. 33-39
Author(s):  
A. E. Nikitin ◽  
E. E. Averin ◽  
D. E. Rozhkov ◽  
A. V. Sozykin ◽  
G. A. Procenko

Aim. To study the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, on lipid levels in patients who receive secondary prevention of cardiovascular diseases (CVD) and require enhanced lipid-lowering therapy.Material and methods. The study included 49 patients (aged of 61.53±1.14 years; 31 [63.3%] men) receiving alirocumab who did not reach the target low density lipoprotein cholesterol (LDL-C) concentrations despite the ongoing optimal lipid-lowering therapy. In all patients, the initial level of lipids was evaluated, as well as their parameters after subsequent alirocumab injections.Results. LDL-C serum level significantly decreased after the first injection compared to the initial level from 2.92±0.22 to 1.65±0.19 mmol/L (p<0.001; Δ45.31±3.61%) and down to 1.74±0.17 mmol/L for the entire study period (p<0.001; Δ41.52±2.69%). The change in LDL-C level between injections did not show statistically significant differences (p=0.141). A direct strong statistically significant correlation between the LDL-C level after the first injection and its average values for the entire observation period was found (r=0.958, p<0.001).Conclusion. The results of the study indicate that the PCSK9 inhibitor, alirocumab, in patients who need secondary prevention of CVD shows a significant additional decrease in the concentration of LDL-C after the first injection. At the same time, approximately half of the patients were able to achieve the recommended levels of LDL-C. The persistence of the achieved low LDL-C levels over time demonstrated that the average concentration of LDL-C during the observation corresponded to the values after the first injection. This finding shows that there is no need for constant monitoring of lipid metabolism parameters when prescribing such therapy.


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