Pub Date : 2022-12-01DOI: 10.1016/j.athplu.2022.07.001
Andreja Rehberger Likozar , Miran Šebeštjen
Background and aims
Elevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab.
Methods
One hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV.
Results
There were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p < 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p < 0.0001) after treatment with PCSK9 inhibitors were observed.
Conclusion
These data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.
{"title":"Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels","authors":"Andreja Rehberger Likozar , Miran Šebeštjen","doi":"10.1016/j.athplu.2022.07.001","DOIUrl":"10.1016/j.athplu.2022.07.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Elevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab.</p></div><div><h3>Methods</h3><p>One hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV.</p></div><div><h3>Results</h3><p>There were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p < 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p < 0.0001) after treatment with PCSK9 inhibitors were observed.</p></div><div><h3>Conclusion</h3><p>These data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/e0/main.PMC9833244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.athplu.2022.08.002
Manuel Odín De los Ríos-Ibarra , José Luis Leiva-Pons , Humberto Rodríguez-Reyes , Marco Antonio Alcocer-Gamba , Jorge Cortés-Lawrenz , Frida María Vizcaíno-Rios , Jaime Barragán-Luna , Julio Iván Farjat-Ruiz , Luis R. Virgen-Carrillo , Francisco Padilla-Padilla , Abel Pavia-López , Enrique C. Morales-Villegas , Natalie C. Ward , Leslie Marisol Lugo-Gavidia
Background and aims
Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aimed to describe the baseline LDL-c levels of patients presenting to cardiovascular clinics and evaluate the proportion who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines.
Methods
The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP.
Results
A total of 5443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid-lowering treatment at entry, while 12.4% were receiving high-intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9 ± 40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–55 mg/dL and 19.3% were achieving LDL-c levels <55 mg/dL. In diabetic patients at very high risk, only 25.7% achieved their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals.
Conclusions
An important number of patients were not receiving any lipid-lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimization of lipid-lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.
{"title":"Risk stratification and lipid evaluation in mexican patients, evidence of lipid and cardiovascular analysis in REMECAR. The mexican registry of cardiovascular diseases (REMECAR group)","authors":"Manuel Odín De los Ríos-Ibarra , José Luis Leiva-Pons , Humberto Rodríguez-Reyes , Marco Antonio Alcocer-Gamba , Jorge Cortés-Lawrenz , Frida María Vizcaíno-Rios , Jaime Barragán-Luna , Julio Iván Farjat-Ruiz , Luis R. Virgen-Carrillo , Francisco Padilla-Padilla , Abel Pavia-López , Enrique C. Morales-Villegas , Natalie C. Ward , Leslie Marisol Lugo-Gavidia","doi":"10.1016/j.athplu.2022.08.002","DOIUrl":"10.1016/j.athplu.2022.08.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aimed to describe the baseline LDL-c levels of patients presenting to cardiovascular clinics and evaluate the proportion who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines.</p></div><div><h3>Methods</h3><p>The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP.</p></div><div><h3>Results</h3><p>A total of 5443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid-lowering treatment at entry, while 12.4% were receiving high-intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9 ± 40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–55 mg/dL and 19.3% were achieving LDL-c levels <55 mg/dL. In diabetic patients at very high risk, only 25.7% achieved their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals.</p></div><div><h3>Conclusions</h3><p>An important number of patients were not receiving any lipid-lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimization of lipid-lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/2c/main.PMC9833238.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.athplu.2022.10.002
Sanna á Borg , Christian Sørensen Bork , Michael René Skjelbo Nielsen , Jan Jóanesarson , Tomas Zaremba , Ihab Bishara Yousef Lolas , Søren Lundbye-Christensen , Peter Søgaard , Erik Berg Schmidt , Albert Marni Joensen
Background and aims
Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls.
Methods
In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18–75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association.
Results
A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause.
Conclusion
We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.
背景和目的关于临床家族性高胆固醇血症(FH)患者冠状动脉钙(CAC)沉积与FH亚型(如多基因原因)之间的关系，目前的知识有限。我们研究了临床FH患者和FH亚型(包括多基因病因)与健康对照的CAC评分。方法在一项病例对照研究中，我们在法罗群岛的全国临床实验室数据库中发现LDL-C为6.7 mmol/l的潜在临床FH病例，并邀请他们根据临床FH评分系统进行诊断评估。对照是在背景人群中确定的。所有受试者年龄在18-75岁之间，无心血管疾病史。在选定的个体中，采用常规方法测定了12种LDL-C相关单核苷酸多态性的FH突变检测和基因型。通过心脏CT评估CAC评分。使用多变量逻辑回归获得的优势比作为关联的度量。结果共纳入120例临床FH患者和117例年龄和性别匹配的对照组。我们发现单基因FH的发生率很低(3%)，但多基因FH的发生率很高(60%)(54%)。CAC评分与临床FH诊断之间有统计学意义的关联，观察到的最高比值比为5.59 (95% CI 1.65;(18.94, p = 0.006)， CAC评分≥300的患者与CAC评分为0的患者相比有显著性差异。在补充分析中，CAC评分与多基因原因的临床FH有很强的相关性。结论:我们发现CAC水平与临床FH之间存在统计学意义上的关联，在假定的多基因原因的临床FH病例中，观察到的风险估计最高。
{"title":"Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia","authors":"Sanna á Borg , Christian Sørensen Bork , Michael René Skjelbo Nielsen , Jan Jóanesarson , Tomas Zaremba , Ihab Bishara Yousef Lolas , Søren Lundbye-Christensen , Peter Søgaard , Erik Berg Schmidt , Albert Marni Joensen","doi":"10.1016/j.athplu.2022.10.002","DOIUrl":"10.1016/j.athplu.2022.10.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls.</p></div><div><h3>Methods</h3><p>In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18–75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association.</p></div><div><h3>Results</h3><p>A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause.</p></div><div><h3>Conclusion</h3><p>We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/8c/main.PMC9833248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.athplu.2022.07.024
Ioanna Gouni-Berthold , Frank Schaper , Ulrike Schatz , Anja Tabbert-Zitzler , Uwe Fraass , Sarah Sauer , Kausik K. Ray
Background and aims
Cardiovascular mortality is high in Germany. For patients with high or very high cardiovascular risk, the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT). This study aimed to assess dyslipidaemia management and achievement of the ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals.
Methods
This European 18-country, cross-sectional, observational DA VINCI study (EUPAS22075) collected data during a single visit between June 2017 and November 2018 and included LLT in the preceding 12 months and the patients' most recent LDL-C measurement. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL-C goals while receiving stabilized LLT was assessed. Data from the German cohort are presented here.
Results
Seven German sites enrolled a total of 421 primary and secondary prevention patients, 327 were receiving stabilized LLT at the time of LDL-C measurement, i.e. statin monotherapy of high (16%; n = 53), moderate (49%; n = 160) or low (7%; n = 24) intensity, ezetimibe combination (18%; n = 58), proprotein convertase subtilisin/kexin type 9 antibody combination (3%; n = 9), and other LLT (7%; n = 23). The 2016 and 2019 risk-based LDL-C goals were attained by 46% (n = 149) and 28% (n = 92) of patients, respectively.
Conclusions
There is a large gap between ESC/EAS recommendations and LDL-C goal achievement in routine clinical practice in high and very high-risk patients in Germany. Low-to-moderate-intensity statin monotherapy was the most frequently used LLT; use of high-intensity statins and combination therapy was limited. In addition to optimizing statin intensity, combination with non-statin LLT may be needed in most of these patients.
{"title":"Low-density lipoprotein cholesterol goal attainment in Germany: Results from the DA VINCI study","authors":"Ioanna Gouni-Berthold , Frank Schaper , Ulrike Schatz , Anja Tabbert-Zitzler , Uwe Fraass , Sarah Sauer , Kausik K. Ray","doi":"10.1016/j.athplu.2022.07.024","DOIUrl":"10.1016/j.athplu.2022.07.024","url":null,"abstract":"<div><h3>Background and aims</h3><p>Cardiovascular mortality is high in Germany. For patients with high or very high cardiovascular risk, the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT). This study aimed to assess dyslipidaemia management and achievement of the ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals.</p></div><div><h3>Methods</h3><p>This European 18-country, cross-sectional, observational DA VINCI study (EUPAS22075) collected data during a single visit between June 2017 and November 2018 and included LLT in the preceding 12 months and the patients' most recent LDL-C measurement. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL-C goals while receiving stabilized LLT was assessed. Data from the German cohort are presented here.</p></div><div><h3>Results</h3><p>Seven German sites enrolled a total of 421 primary and secondary prevention patients, 327 were receiving stabilized LLT at the time of LDL-C measurement, i.e. statin monotherapy of high (16%; n = 53), moderate (49%; n = 160) or low (7%; n = 24) intensity, ezetimibe combination (18%; n = 58), proprotein convertase subtilisin/kexin type 9 antibody combination (3%; n = 9), and other LLT (7%; n = 23). The 2016 and 2019 risk-based LDL-C goals were attained by 46% (n = 149) and 28% (n = 92) of patients, respectively.</p></div><div><h3>Conclusions</h3><p>There is a large gap between ESC/EAS recommendations and LDL-C goal achievement in routine clinical practice in high and very high-risk patients in Germany. Low-to-moderate-intensity statin monotherapy was the most frequently used LLT; use of high-intensity statins and combination therapy was limited. In addition to optimizing statin intensity, combination with non-statin LLT may be needed in most of these patients.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10533990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI).
Methods
We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level.
Results
One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan–Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06–3.45, p = 0.03) on events than other known atherosclerosis risk factors.
Conclusions
The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words)
{"title":"The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction","authors":"Jun Sawaguchi , Yasuhiko Saeki , Minako Oda , Taka-aki Takamura , Kosuke Fujibayashi , Minoru Wakasa , Hironobu Akao , Michihiko Kitayama , Yasuyuki Kawai , Kouji Kajinami","doi":"10.1016/j.athplu.2022.09.002","DOIUrl":"10.1016/j.athplu.2022.09.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI).</p></div><div><h3>Methods</h3><p>We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level.</p></div><div><h3>Results</h3><p>One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both <em>p</em> < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan–Meier analysis (<em>p</em> = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06–3.45, <em>p</em> = 0.03) on events than other known atherosclerosis risk factors.</p></div><div><h3>Conclusions</h3><p>The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words)</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/02/main.PMC9833232.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.athplu.2022.08.001
Jean Ferrières , Michel Farnier , Eric Bruckert , Alexandre Vimont , Vincent Durlach , Emile Ferrari , Antonio Gallo , Franck Boccara , Dorota Ferrières , Sophie Béliard
Background and aims
Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL).
Methods
We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system.
Results
The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention.
Conclusions
The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.
{"title":"Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia","authors":"Jean Ferrières , Michel Farnier , Eric Bruckert , Alexandre Vimont , Vincent Durlach , Emile Ferrari , Antonio Gallo , Franck Boccara , Dorota Ferrières , Sophie Béliard","doi":"10.1016/j.athplu.2022.08.001","DOIUrl":"10.1016/j.athplu.2022.08.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL).</p></div><div><h3>Methods</h3><p>We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system.</p></div><div><h3>Results</h3><p>The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention.</p></div><div><h3>Conclusions</h3><p>The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/e1/main.PMC9833221.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/j.athplu.2022.07.016
M. Dorrian
{"title":"A primary Care based Familial Hypercholesterolaemia screening service in Guernsey, from concept to delivery","authors":"M. Dorrian","doi":"10.1016/j.athplu.2022.07.016","DOIUrl":"10.1016/j.athplu.2022.07.016","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089522000360/pdfft?md5=287eb33404decf7933a04cb4f3ec361a&pid=1-s2.0-S2667089522000360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48621711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/j.athplu.2022.07.019
A. Pottle, T. Gondo, C. Huggett, L. Jones, T. Khan, S. Mower, E. Neves, J. Senior, J. Wagg, M. Barbir
{"title":"I used to dream that my cholesterol could be in single figures, and now it is!!!","authors":"A. Pottle, T. Gondo, C. Huggett, L. Jones, T. Khan, S. Mower, E. Neves, J. Senior, J. Wagg, M. Barbir","doi":"10.1016/j.athplu.2022.07.019","DOIUrl":"10.1016/j.athplu.2022.07.019","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089522000396/pdfft?md5=b94837006120e1725a82b2cbb09c3de9&pid=1-s2.0-S2667089522000396-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43933838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/j.athplu.2022.07.022
C. Tucker, S. Barrett, S. Pattman
{"title":"An outreaching lipid clinic model supporting PCSK9i uptake and lipid optimisation in secondary prevention across primary/secondary care interface","authors":"C. Tucker, S. Barrett, S. Pattman","doi":"10.1016/j.athplu.2022.07.022","DOIUrl":"10.1016/j.athplu.2022.07.022","url":null,"abstract":"","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089522000426/pdfft?md5=0759cacbf84f696def0df0889aa25acc&pid=1-s2.0-S2667089522000426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45766222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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