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%.

4944The contribution of familial hypercholesterolemia (FH) to premature coronary artery disease decreased by 2-fold between 1998 and 2018 in a founder population with high prevalence of FH

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Lauziere ◽  
D Brisson ◽  
S Bedard ◽  
E Khoury ◽  
G Tremblay ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Founder Population ◽  
High Prevalence ◽  
Artery Disease ◽  
The Impact

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant trait associated with high risk of premature coronary artery disease (CAD). The worldwide prevalence of FH is estimated at 1:250 to 1:500. In certain populations, including French Canadians (FC), the prevalence is significantly higher however. From 1995 to 1998, FH contributed to 9.6% of angiographically proven CAD in a FC founder population, the burden being the highest in men aged <50 years (20.6%). In the past 2 decades, powerful statins, ezetimibe and other low-density lipoprotein-Cholesterol (LDL-C) modulators, such as PCSK9 inhibitors, have been progressively introduced and several FH diagnosis scoring systems or guidelines have been developed and disseminated in order to facilitate FH recognition and management. The impact of these measures on the FH burden is however not documented. Purpose To compare the burden of FH twenty years apart in FC patients hospitalized for CAD. Methods Lipid profiles, cardiovascular risk factors and FH status of 1,132 FC patients who were hospitalized for a CAD event and who consecutively attended the cardiovascular disease clinic in 2017 and 2018 were compared to those of 2,506 who consecutively presented angiographically proven CAD two decades ago. FH status was based on Simon Broome and FH Canada definitions. In 1998, all consenting CAD patients were also molecularly screened for the most prevalent FH causing mutations in FC. Comparisons between groups were performed using Chi-square and independent samples Student's t-test. Results Most patients in both cohorts were males (74.5% vs 73.9% in 1998 vs. 2018, respectively). At admission, mean LDL-C (± SD) was 3.99±1.67 in 1998 vs. 2.22±1.06 in 2018 (p<0.001). The proportion of patients who were treated with a statin or another lipid lowering agent was 32.9% in 1998 compared to 67.6% in 2018 (p<0.001) and the drug regimen was also significantly different. In 1998, 24.6% of patients had LDL-C >5.0 mmol/L at admission compared to 4.2% in 2018. Definite FH was diagnosed in 9.6% of patients in the 1998 cohort compared to 4.7% in the 2018 cohort (p<0.001). FH patients hospitalized for CAD were significantly older in 2018 than in 1998 (56.3±11.3 vs. 49.2±10.9 in men, p=0.001; 61.1±11.8 vs. 53.2±12.3 in women, p=0.02). In the same period, the relative burden of diabetes and other lipid disorders, including high-density lipoprotein dysmetabolism significantly increased (p<0.001). Conclusions Over a period of 20 years, in a founder population with a high prevalence of FH, the contribution of FH to hospitalizations for CAD decreased by 2-fold and affected patients now tend to be hospitalized at an older age than 2 decades ago. This suggests that early diagnosis and more effective management of FH in the last 2 decades have contributed to significantly decrease its burden. Acknowledgement/Funding ECOGENE-21, Amgen, Sanofi

scholarly journals Response to Polygenic Risk: Results of the MyGeneRank Mobile Application-Based Coronary Artery Disease Study

2021 ◽  
Author(s):  
Evan D. Muse ◽  
Shang-Fu Chen ◽  
Shuchen Liu ◽  
Brianna Fernandez ◽  
Brian Schrader ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Risk ◽  
Lipid Lowering ◽  
P Value ◽  
Lipid Lowering Therapy ◽  
Polygenic Risk ◽  
Lowering Therapy ◽  
Artery Disease

AbstractThe degree to which polygenic risk scores (PRS) influence preventive health is the subject of debate, with few prospective studies completed to date. We developed a smartphone application for the prospective and automated generation, communication, and electronic capture of response to a PRS for coronary artery disease (CAD). We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid lowering therapy (NCT03277365). 20% of high genetic risk (n=95) vs 7.9% of low genetic risk individuals (n=101) initiated lipid lowering therapy at follow-up (p-value = 0.002). The initiation of both statin and non-statin lipid lowering therapy was associated with degree of genetic risk – 15.2% (n=92) vs 6.0% (n=100) for statins (p-value = 0.018) and 6.8% (n=118) vs 1.6% (n=123) for non-statins (p-value = 0.022) in high vs low genetic risk, respectively. Overall, degree of genetic risk was associated with use of any lipid lowering therapy at follow-up - 42.4% (n=132) vs 28.5% (n=130) (p-value = 0.009). We also find that CAD PRS information is perceived to be understandable, actionable, and does not induce health anxiety.

scholarly journals A case of familial hypercholesterolemia with premature coronary artery disease

Heart India ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 156
Author(s):  
DigvijayDeeliprao Nalawade ◽  
JaywantM Nawale ◽  
AjayS Chaurasia ◽  
Dhirendra Tiwari
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Premature Coronary Artery Disease ◽  
Artery Disease

Long-term prognosis after percutaneous or surgical revascularization in patients with diabetes mellitus and complex coronary artery disease- a systematic review and meta analysis

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
S Mandava ◽  
S Pothuru ◽  
S Adeel Hassan ◽  
D Missael Rocha Castellanos ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Artery Bypass ◽  
Left Main ◽  
All Cause Mortality ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background-Whether Coronary artery bypass grafting (CABG) confers a survival benefit in patients with diabetes mellitus(DM) and complex coronary artery disease (CAD), including left main CAD and multivessel coronary disease (MVD) after a follow up period ≥ 5 years remains unknown. Methods- Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception to December 12th 2020. Using a generic invariance weighted random effects model, Hazard ratios (HRs) and their 95% confidence intervals (CIs) from individual studies were converted to Log HRs and corresponding standard errors, which were then pooled. The primary outcome of interest was all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) which was defined as a composite of death, myocardial reinfarction and stroke at ≥ 5 years. Results-A total of 8 studies with 13336 participants(PCI = 6783, CABG = 6553)were included in our analysis. Mean age was 54.6 and 55.3 in the PCI-DES and CABG groups respectively. The 5-yr follow-up outcomes including all-cause mortality (HR 1.37; 95%CI 1.15-1.65; p = 0.0006, I2 = 0)and MACCE (HR 1.48; 95%CI 1.29-1.69; p &lt; 0.00001, I2 = 0) were significantly higher with PCI as compared to CABG. Furthermore, at &gt;5 year follow-up, all-cause mortality (HR 1.35; 95%CI 1.10-1.66; p = 0.004, I2 = 37) and MACCE (HR 1.98; 95%CI 1.85-2.12; p &lt; 0.00001, I2 = 0) had similar outcomes. Conclusion-Amongst patients with DM and Complex CAD ( left main/MVD), CABG was associated with improved long-term mortality and freedom from MACCEs as opposed to PCI-DES. CABG is the preferred revascularization strategy in patients with complex anatomic disease and concurrent diabetes. Abstract Figure.

scholarly journals Familial Hypercholesterolaemia With Premature Coronary Artery Disease: A Case Report

2020 ◽  
Vol 1 (3-4) ◽  
pp. 150-153
Author(s):  
Chandramukhi Sunehra ◽  
Krishnaswamy Raghu
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systolic Function ◽  
Color Doppler ◽  
Artery Bypass ◽  
Density Lipoprotein ◽  
Left Ventricular ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Artery Disease

A young, 18-year-old lady presented with history of chest pain on exertion typical of angina. General examination revealed multiple tendon xanthomas. Systemic examination was unremarkable. Electrocardiogram showed segment (ST) depression in inferior and lateral leads. Echocardiogram revealed normal left ventricular systolic function and no left ventricular regional wall motion abnormalities. Diastolic flow turbulence was noted in the left main coronary artery and proximal left anterior descending artery on color Doppler interrogation across the coronary arteries. Lipid profile showed unusually high total cholesterol and low-density lipoprotein cholesterol. Subsequent evaluation with coronary angiogram revealed triple vessel coronary artery disease. The patient underwent coronary artery bypass surgery and is on antiplatelet and lipid-lowering drug therapy.

P5508Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Yamamoto ◽  
H Otake ◽  
T Shinke ◽  
T Yamashita ◽  
H Kawamori ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Plaque ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Plaque Vulnerability ◽  
Glucose Fluctuation ◽  
Fibrous Cap ◽  
Lipid Rich Plaque ◽  
Artery Disease

Abstract Background Diabetes mellitus has been known as an important factor of coronary artery disease (CAD) progression despite of widespread with lipid-lowering therapy. Although we have reported that large glucose fluctuation is associated with the development of cardiovascular disease in both diabetes mellitus (DM) and non-DM patients, the underlying mechanisms remain unclear. Monocytes play a key role for atherosclerotic plaque formation. Monocytes in human peripheral blood are divided into three subsets: CD14++CD16− monocytes, CD14++CD16+ monocytes, and CD14+CD16++ monocytes. The CD14++CD16+ monocyte subset has recently received attention because it is reported to be associated with future cardiovascular events such as acute myocardial infarction. However, their impact on coronary plaque vulnerability in coronary artery disease (CAD) patients with or without DM remains unclear. Purpose The aim of this study was to investigate the impact of CD14++CD16+ monocyte levels on coronary plaque vulnerability and glucose fluctuation in stable CAD patients with well-regulated lipid levels. Methods This prospective observational study included 50 consecutive patients with CAD (DM [n=22], Non-DM [n=28]), receiving lipid-lowering therapy and undergoing coronary angiography and optical coherence tomography (OCT). Patients were divided into 3 tertiles according to the CD14++CD16+ monocyte percentages assessed by flow cytometry. Standard OCT parameters including lipid arc, lipid length, fibrous cap thickness (FCT) on lipid rich plaque, were assessed for 97 angiographically intermediate lesions (diameter stenosis: 30–70%). The presence of thin-cap fibroatheroma (TCFA), defined as a thin fibrous cap (<65μm) overlying a lipid-rich plaque (>90°), was also assessed. Daily glucose fluctuation assessed by using continuous glucose monitoring system was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). Results CD14++CD16+ monocytes negatively correlated with FCT on lipid rich plaque (r=0.508, p<0.01) (Figure. 1). The presence of thin-cap fibroatheroma (TCFA) was increased stepwise according to the tertile of CD14++CD16+ monocytes (0 [tertile 1] vs. 5 [tertile 2] vs. 10 [tertile 3], p<0.01). CD14++CD16+ monocytes were a significant determinant of TCFA (OR 1.279, p=0.001). Although CD14++CD16+ monocytes were not significantly correlated with MAGE in DM patients (r=0.259, p=0.244), a significant relationship was found between CD14++CD16+ monocytes and MAGE in non-DM patients (r=0.477, p=0.018) (Figure 2). Conclusions CD14++CD16+ monocytes were associated with coronary plaque vulnerability in CAD patients with well-regulated lipid levels both in DM and non-DM patients. Cross-talk between glucose fluctuation and CD14++CD16+ monocytes may enhance plaque vulnerability, particularly in non-DM patients. CD14++CD16+ monocytes could be a possible therapeutic target for coronary plaque stabilization.

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