The use of lipid-lowering therapies should be considered in paediatric patients at high risk of atherosclerosis

2010 ◽  
Vol 26 (12) ◽  
pp. 9-11
Author(s):  
&NA;
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hermann Yao ◽  
Michel Farnier ◽  
Laura Tribouillard ◽  
Frédéric Chague ◽  
Philippe Brunel ◽  
...  

Abstract Background Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. Methods The data for all consecutive patients hospitalized in 2012–2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0–2) (n = 234) after matching for age, sex, and diabetes (1:2). Results Although LDL-cholesterol was high (208 [174–239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090–3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014–1.057, P = 0.001). Conclusions FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
H Subbiah Ponniah ◽  
M Ahmed ◽  
T Edwards ◽  
J Cobb ◽  
E Dean ◽  
...  

Abstract Introduction There are now over 2.5 million NHS patients awaiting elective surgery, with the most in orthopaedics. We present an algorithm and results for safely and equitably restarting surgery at COVID-light sites. Method An MDT applied the COVID-19 Algorithm for Resuming Elective Surgery (CARES) on 1169 patients awaiting elective orthopaedic surgery. It assessed safety, procedural efficacy, and biopsychosocial factors, to prioritise patients. They were assigned to five categories and underwent surgery at one of three COVID-light sites (1. access to HDU/ITU/Paediatrics/specialist equipment, 2. an NHS elective surgical unit and 3. a private elective surgical unit). Results 21 ‘Urgent’ patients received expedited care; 118 were Level 1/2; 222 were Level 3; 808 were Level 4. In 6 weeks, 355 surgeries were performed, with Urgent and Level 1/2 cases performed soonest (mean 18 days, p < 0.001). 33 high-risk/complex/paediatric patients had surgery at Site 1 and the rest at Sites 2 and 3. No patients contracted COVID-19 within 2 weeks of surgery. Conclusions We validated a widely generalisable model to facilitate resumption of elective surgery in COVID-light sites. It enabled surgery for patients in most suffering, undergoing the most efficacious procedures and/or at highest risk of deterioration, without compromising patient-safety.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
S Bray ◽  
A.L Catapano ◽  
N Poulter ◽  
G Villa

Abstract Background/Introduction For patients at very-high risk of cardiovascular (CV) events, the 2016 ESC/EAS dyslipidaemia guidelines recommended lipid-lowering therapy (LLT) to achieve an LDL-C level below 70 mg/dL. This was lowered to an LDL-C level below 55 mg/dL in the 2019 guidelines. Purpose To assess: 1) the risk profile of European patients with established atherosclerotic CV disease (ASCVD) receiving LLT; and 2) the treatment gap between the estimated risk and the population benefits if all patients were to achieve LDL-C levels of 70 mg/dL and 55 mg/dL. Methods We used data from Da Vinci, an observational cross-sectional study conducted across 18 European countries. Data were collected at a single visit between June 2017 and November 2018, for consented adults who had received any LLT in the prior 12 months and had an LDL-C measurement in the prior 14 months. LDL-C level was assessed at least 28 days after starting the most recent LLT (stabilised LLT). For each patient with established ASCVD receiving stabilised LLT, we: 1) calculated their absolute LDL-C reduction required to achieve LDL-C levels of 70 mg/dL and 55 mg/dL; 2) predicted their 10-year CV risk using the REACH score based on demographic and medical history; 3) simulated their relative risk reduction (RRR) by randomly sampling from the probability distribution of the rate ratio per 38.7 mg/dL (1 mmol/L) estimated by the Cholesterol Treatment Trialists Collaboration meta-analysis; and 4) calculated their absolute risk reduction (ARR) achieved by meeting LDL-C levels of 70 mg/dL and 55 mg/dL. Results A total of 2039 patients with established ASCVD were included in the analysis. Mean (SD) LDL-C was 83.1 (35.2) mg/dL. 40.4% and 19.3% of patients achieved LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. Mean (SD) 10-year CV risk calculated using the REACH score was 36.3% (15.4%). Mean absolute LDL-C reductions of 19.6 mg/dL and 30.4 mg/dL were needed to reach LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. When adjusted for the LDL-C reduction required to achieve an LDL-C level of 70 mg/dL, mean ARR was 3.0%, leaving a mean (SD) residual 10-year CV risk of 33.3% (15.5%). When adjusted for the LDL-C reduction required to achieve an LDL-C level of 55 mg/dL, mean ARR was 4.6%, leaving a mean (SD) residual 10-year CV risk of 31.7% (15.2%). Conclusion(s) In a contemporary European cohort with ASCVD receiving LLT, the 10-year risk of CV events is high and many patients do not achieve LDL-C levels of 55 mg/dL or even of 70 mg/dL. Moreover, even if all patients were to achieve recommended LDL-C levels, they would still remain at a high residual risk of CV events. These data suggest these patients require even more intensive LLT. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen


2011 ◽  
Vol 19 (4) ◽  
pp. 781-794 ◽  
Author(s):  
Jeong Euy Park ◽  
Chern-En Chiang ◽  
Muhammad Munawar ◽  
Gia Khai Pham ◽  
Apichard Sukonthasarn ◽  
...  

Background: Treatment of hypercholesterolaemia in Asia is rarely evaluated on a large scale, and data on treatment outcome are scarce. The Pan-Asian CEPHEUS study aimed to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among patients on lipid-lowering therapy. Methods: This survey was conducted in eight Asian countries. Hypercholesterolaemic patients aged ≥18 years who had been on lipid-lowering treatment for ≥3 months (stable medication for ≥6 weeks) were recruited, and lipid concentrations were measured. Demographic and other clinically relevant information were collected, and the cardiovascular risk of each patient was determined. Definitions and criteria set by the updated 2004 National Cholesterol Education Program guidelines were applied. Results: In this survey, 501 physicians enrolled 8064 patients, of whom 7281 were included in the final analysis. The mean age was 61.0 years, 44.4% were female, and 85.1% were on statin monotherapy. LDL-C goal attainment was reported in 49.1% of patients overall, including 51.2% of primary and 48.7% of secondary prevention patients, and 36.6% of patients with familial hypercholesterolaemia. The LDL-C goal was attained in 75.4% of moderate risk, 55.4% of high risk, and only 34.9% of very high-risk patients. Goal attainment was directly related to age and inversely related to cardiovascular risk and baseline LDL-C. Conclusion: A large proportion of Asian hypercholesterolaemic patients on lipid-lowering drugs are not at recommended LDL-C levels and remain at risk for cardiovascular disease. Given the proven efficacy of lipid-lowering drugs in the reduction of LDL-C, there is room for further optimization of treatments to maximize benefits and improve outcomes.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jacob Hartz ◽  
Ronald M. Krauss ◽  
Mikael Göttsater ◽  
Olle Melander ◽  
Peter Nilsson ◽  
...  

Background. Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods. Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results. The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions. The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.


2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
David M Kern ◽  
Sanjeev Balu ◽  
Ozgur Tunceli ◽  
Swetha Raparla ◽  
Deborah Anzalone

Introduction: This study aimed to compare the demographic and clinical characteristics of patients with different risk factors for CHD as defined by NCEP ATP III guidelines. Methods: Dyslipidemia patients (≥1 medical claim for dyslipidemia, ≥1 pharmacy claim for a statin, or ≥1 LDL-C value ≥100 mg/dL [index date]) aged ≥18 y were identified from the HealthCore Integrated Research Environment from 1/1/2007-7/31/2012. Patients were classified as low risk (0 or 1 risk factor): hypertension, age ≥45 y [men] or ≥55 y [women], or low HDL-C), moderate/moderately high risk (≥2 risk factors), high risk (having CHD or CHD risk equivalent), or very high risk (having ACS or other established cardiovascular disease plus diabetes or metabolic syndrome). Demographics, comorbidities, medication use and lipid levels during the 12 months prior, and statin use during the 6 months post-index date were compared across risk groups (very high vs each other risk group). Results: There were 1,524,351 low-risk (mean age: 47 y; 45% men), 242,357 moderate-risk (mean age: 58 y; 59% men), 188,222 high-risk (mean age: 57 y; 52% men), and 57,469 very-high-risk (mean age: 63 y; 61% men) patients identified. Mean Deyo-Charlson comorbidity score differed greatly across risk strata: 0.20, 0.33, 1.26, and 2.22 from low to very high risk (p<.0001 for each). Compared with high-risk patients, very-high-risk patients had a higher rate of ischemic stroke: 5.4% vs 4.1%; peripheral artery disease: 17.1% vs 11.6%; coronary artery disease: 8.5% vs 8.2%; and abdominal aortic aneurysm: 2.3% vs 2.0% (p<.05 for each). Less than 1% of the total population had a prior prescription for each non-statin lipid-lowering medication (bile acid sequestrants, fibrates, ezetimibe, niacin, and omega-3). Very-high-risk patients had lower total cholesterol (very-high-risk mean: 194 mg/dL vs 207, 205, and 198 mg/dL for low-, moderate-/moderately-high-, and high-risk patients, respectively) and LDL-C (very-high-risk mean: 110 mg/dL vs 126, 126, and 116 mg/dL for the other risk groups; p<.0001 for each); higher triglycerides (TG) (very-high-risk mean: 206 mg/dL vs 123, 177, and 167 mg/dL for the other groups; p<.0001 for each); and lower HDL-C (very-high-risk mean: 45 mg/dL vs 57 [p<.0001], 45 [p=.006], and 51 mg/dL [p<.0001]). Statin use was low overall (15%), but higher in the very-high-risk group (45%) vs the high- (29%), moderate-/moderately-high- (18%), and low- (12%) risk groups (p<.0001 for each). Conclusions: Despite a large proportion of patients having high lipid levels, statin use after a dyslipidemia diagnosis was low: ≥80% of all patients (and more than half at very high risk) failed to receive a statin, indicating a potentially large population of patients who could benefit from statin treatment. Prior use of non-statin lipid-lowering medications was also low considering the high TG and low HDL-C levels among high-risk patients.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.


BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019041 ◽  
Author(s):  
Farshid Hajati ◽  
Evan Atlantis ◽  
Katy J L Bell ◽  
Federico Girosi

ObjectivesWe examine the extent to which the adult Australian population on lipid-lowering medications receives the level of high-density lipoprotein cholesterol (HDL-C) testing recommended by national guidelines.DataWe analysed records from 7 years (2008–2014) of the 10% publicly available sample of deidentified, individual level, linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) electronic databases of Australia.MethodsThe PBS data were used to identify individuals on stable prescriptions of lipid-lowering treatment. The MBS data were used to estimate the annual frequency of HDL-C testing. We developed a methodology to address the issue of ‘episode coning’ in the MBS data, which causes an undercounting of pathology tests. We used a published figure on the proportion of unreported HDL-C tests to correct for the undercounting and estimate the probability that an HDL-C test was performed. We judged appropriateness of testing frequency by comparing the HDL-C testing rate to guidelines’ recommendations of annual testing for people at high risk for cardiovascular disease.ResultsWe estimated that approximately 49% of the population on stable lipid-lowering treatment did not receive any HDL-C test in a given year. We also found that approximately 19% of the same population received two or more HDL-C tests within the year. These levels of underutilisation and overutilisation have been changing at an average rate of 2% and −4% a year, respectively, since 2009. The yearly expenditure associated with test overutilisation was approximately $A4.3 million during the study period, while the cost averted because of test underutilisation was approximately $A11.3 million a year.ConclusionsWe found that approximately half of Australians on stable lipid-lowering treatment may be having fewer HDL-C testing than recommended by national guidelines, while nearly one-fifth are having more tests than recommended.


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