Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients with familial hypercholesterolemia

2019 ◽  
pp. 204748731988098 ◽  
Author(s):  
Ye-Xuan Cao ◽  
Hui-Hui Liu ◽  
Jing-Lu Jin ◽  
Di Sun ◽  
Yuan-Lin Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Coronary Artery Calcification ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipid Lowering Therapy ◽  
Gensini Score ◽  
Proprotein Convertase

Aims Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. Methods A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. Results Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan–Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11–1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. Conclusions Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.

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

Abstract 18995: Statins in Familial Hypercholesterolemia - Effects on Coronary Artery Disease and All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Joost Besseling ◽  
Gerard K Hovingh ◽  
John J Kastelein ◽  
Barbara A Hutten
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Lipid Lowering Therapy ◽  
Time Varying ◽  
All Cause Mortality ◽  
Artery Disease

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.

scholarly journals SAT-566 Avoiding the Heartache: A Case of Familial Hypercholesterolemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mustafa Kinaan ◽  
Arelys Ramos Rivera ◽  
Hanford Yau
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Risk Stratification ◽  
Total Cholesterol ◽  
Cardiovascular Events ◽  
Total Cholesterol Level ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
History Of

Abstract More than 70% of individuals with atherosclerotic cardiovascular disease are believed to have underlying gene-linked mechanisms leading to hyperlipidemia. It is estimated that 1 in 200 individuals in the United States has heterozygous Familial Hypercholesterolemia (FH). We present a case that highlights the importance of comprehensive care for a patient with heterozygous FH, from screening and risk stratification, to therapy. Our patient is a 43-year-old gentleman with history of hyperlipidemia. At age 25, he was diagnosed with hyperlipidemia and was started on statin therapy. He has strong family history of cardiovascular disease. His mother had her first myocardial infarction (MI) at age 40 and required coronary artery bypass. She also suffered from three strokes. His maternal aunt and uncle suffered from MIs at age 38 and 40, respectively. Additionally, his maternal grandfather passed away from MI at age 38. The patient’s daughter was found to have total cholesterol level &gt; 300 mg/dL at age 8. He does not have history of obesity, diabetes, previous cardiovascular events, or hypothyroidism. He is athletic and follows a healthy diet. He did not have any xanthomas, xanthelasmas, nor arcus cornealis. At time of initial evaluation, the patient had low-density lipid (LDL) level of 180 mg/dL despite therapy with rosuvastatin, ezetimibe, and niacin. Based on these findings, we proceeded with genetic testing. Results of testing showed a heterozygous c.6delG (p.Trp4Glyfs*202) pathogenic mutation of the LDL receptor. We also obtained cardiovascular risk stratification studies. On cardiac CT angiogram, he was found to have extensive, four-vessel disease with 80-90% stenosis of the left ascending artery (LAD) with coronary calcium score of 136 and total score of 219 (99th percentile). Exercise, stress myocardial perfusion scan showed small reversible anteroseptal perfusion abnormality suggestive of mild to moderate ischemia. LAD stenosis was confirmed on a left heart catheter, but no intervention was required. We proceeded with aggressive lipid-lowering therapy with rosuvastatin 40mg daily and alirocumab 300mg monthly. He was also started on aspirin and beta-blocker given coronary artery disease. Following initiation of therapy, the patient’s LDL level dropped to 51 mg/dL with total cholesterol level of 153 mg/dL, HDL of 47mg/dL, and triglycerides of 109 mg/dL. The patient was encouraged to seek genetic counseling for his children and first degree relatives. His daughter was started on rosuvastatin 7.5mg daily by her pediatrician. The patient has not suffered any cardiovascular events and continues to follow up for therapy. Without aggressive lipid-lowering therapy, the lifespan of FH patients can be significantly shortened. Therefore, identifying FH patients is imperative to prevent cardiovascular disease in these patients and their afflicted family members.

Atherosclerotic Cardiovascular Risk in Adult Patients with Hemophilia: What We Can Do to Reduce Risk of Cardiovascular Events? Implementation of 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol in Patients with Hemophilia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4687-4687
Author(s):  
Kamila Izabela Cisak ◽  
Jianmin Pan ◽  
Shesh Nath Rai ◽  
Patricia Ashby ◽  
Vivek R. Sharma
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction Hemophilia A and B are genetic disorders characterized by deficiency of clotting factors resulting in delayed bleeding. Despite hypocoagulable state, patients with hemophilia are prone to developing coronary artery disease or its equivalents. It is known that proper treatment of dyslipidemia has relevant impact of atherosclerotic cardiovascular events reduction. The goal of our study was to determine implementation of newest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol in our patients with hemophilia and assess how many more patients currently may require lipid-lowering therapy. Methods We performed retrospective chart review of patients followed at single hemophilia treatment center in United States. We included 30 patients with factor VIII or IX deficiency, age 30 and older, followed in clinic between 2005 and 2014 with available lipid profile results. Patients with acquired hemophilia were excluded from study. We used stepwise approach proposed by above guidelines and divided patients into four groups. Results 4 patients among 30 were already on lipid lowering therapy. 1 (3.3%) additional patient [95% CI 0.001-0.17] required lipid lowering therapy due to presence of clinical atherosclerotic cardiovascular disease (group 1), 0 patients had LDL-C at least 190 mg/dl (group 2), 2 (6.7%) additional patients [95% CI 0.008-0.21] required therapy due to presence of diabetes mellitus and 40 to 75 year of age and LDL-C levels of 70 to 189 mg/dl (group 3); 9 (30%) additional patients [95% CI 0.17-0.51] should receive therapy due to age 40 to 75 and estimated 10-year ASCVD risk above 7.5%. We had total 12 (40%) additional patients among 30 with known lipid profile who were not on lipid lowering therapy but who require such therapy based on the latest 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. Conclusion Aggressive cardiovascular risk factor modifications play a significant role in prevention of coronary artery disease, stroke and peripheral vascular disease. This may be even more relevant in patients with hemophilia who have an increased baseline risk of bleeding and may therefore be at greater risk of complications from anti-thrombotic therapies used for treating cardiovascular disease. Above results suggest that according to actual 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol, a significant number of patients with hemophilia may require lipid lowering therapy. It is important for hemophilia treatment centers to screen their patients with regard to this since many of them may either not have primary care physicians or may not be perceived as having high risk for cardiovascular disease due to their bleeding disorder. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prevalence, prescriptions, outcomes and costs of type 2 diabetes patients with or without prior coronary artery disease or stroke: a longitudinal 5-year claims-data analysis of over 7 million inhabitants

2021 ◽  
Vol 12 ◽  
pp. 204062232110263
Author(s):  
Aldo Pietro Maggioni ◽  
Letizia Dondi ◽  
Felicita Andreotti ◽  
Giulia Ronconi ◽  
Silvia Calabria ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Hospital Admissions ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Recommended Treatment ◽  
Artery Disease

Aims: To analyze the prevalence, comorbidities, outcomes and costs of type 2 diabetes mellitus (T2DM) patients with and without coronary artery disease (CAD) or stroke in a population of over 7 million inhabitants. Methods: T2DM patients were identified in 2015 (accrual period) from the Ricerca e Salute (ReS) database linking administrative records to demographics. Based on 2013–2015 information, four cohorts were considered: #1 with CAD and/or stroke; #2 without CAD and/or stroke; #3 with chronic CAD but no myocardial infarction or stroke; #4 with chronic CAD undergoing percutaneous coronary interventions (PCI). Hospitalizations, drugs and other outpatient care were assessed from 2015 to 2017. Results: The prevalence of T2DM was 6% (441,085/7,365,954). CAD and/or stroke in the previous 3 years affected 7.5% of T2DM patients (33,153); this cohort was generally older, of male sex, with more comorbidities, prescriptions, and hospital admissions (50.5% versus 13.4% during the first follow-up year) compared to cohort #2. Yearly costs were over three-fold for cohort #1 versus #2, main drivers being hospitalizations in the former and drugs in the latter. Two-year cardiovascular events were recorded significantly more commonly in cohort #4 compared to the other cohorts. Guideline-recommended lipid-lowering therapy was <80% in all but cohort #4. Conclusions: The present analysis points to three areas of potential improvement in T2DM management: (a) guideline-recommended treatment patterns of T2DM patients; (b) three-fold recurrences and costs in T2DM patients with, compared to those without, prior cardiovascular events; (c) high event rates associated with chronic CAD and PCI, warranting specific studies aimed at improved prevention.

scholarly journals Familial hypercholesterolemia: case series of a rare condition

2021 ◽  
Vol 26 (3S) ◽  
pp. 4610
Author(s):  
O. P. Ishevskaia ◽  
A. M. Namitokov ◽  
S. V. Kruchinova ◽  
E. D. Kosmacheva
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Genetic Research ◽  
Case Series ◽  
Young Age ◽  
Diagnostic Methods ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy

Introduction. Cardiovascular events at a young age are often the first manifestation of a genetic disorder such as familial hypercholesterolemia. High cholesterol levels, xanthomas and xanthelasmas, as well as a positive family history of cardiovascular disease, make it possible to identify a group of patients subject to genetic research. The identification of a specific mutation helps to determine further strategy not only for a patient, but also to his or her immediate relatives, thereby effectively conducting both secondary and primary prevention of atherosclerosis complications.Brief description. Using the example of patients from the Krasnodar Lipid Center, the relevance of genetic testing and cascade screening is demonstrated. We show problems of delayed diagnosis and low medical adherence, as well as the ways to optimize care for patients with genetic lipid metabolism disorders.Discussion. The rise in the incidence of cardiovascular events at a young age in developed countries prompts the search for more improved screening and diagnostic methods for familial hypercholesterolemia. The optimal age of initiation of lipid-lowering therapy in children with established familial hypercholesterolemia is also discussed. While secondary prevention appears to be clearer, there is still insufficient achievement of low-density lipoprotein cholesterol targets in patients with a previous cardiovascular event.

Abstract 16263: Association Between Visit-to-Visit Lipid Variability and Cardiovascular Events in Patients With Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yexuan Cao ◽  
Ruixia Xu ◽  
Huiwen Zhang ◽  
Jinglu Jin ◽  
Huihui Liu ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Prognostic Value ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Major Adverse Cardiovascular Events ◽  
Lipid Lowering Therapy ◽  
Cox Analysis

Introduction: Visit-to-visit variability in lipid has been suggested as an predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). Hypothesis: This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy. Methods: A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM). Results: During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In multivariate Cox analysis, only Lp(a) variability parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival (Log-rank p <0.05). The results were consistent in various subgroups. Conclusions: This is the first report to evaluate the prognostic value of lipid variability in real-world patients with FH and showed that Lp(a), but not LDL-C variability, was associated with MACEs, which emphasized the importance of regular lipid monitoring in patients with high risk.

Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk

2019 ◽  
Vol 26 (12) ◽  
pp. 1262-1270 ◽  
Author(s):  
Seohyuk Lee ◽  
Leo E Akioyamen ◽  
Sumayah Aljenedil ◽  
Jean-Baptiste Rivière ◽  
Isabelle Ruel ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Odds Ratio ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
The Impact

Aims Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of ‘definite familial hypercholesterolemia’, 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. Methods We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. Results After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28–80%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7–2.5% of subjects with an LDL-C > 4.9 mmol/L (190 mg/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n = 4181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75–9.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34–8.26), compared with controls. Conclusion DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change.

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