P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Peripheral Artery Disease ◽  
Cardiac Death ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Lowering Therapy ◽  
Artery Disease

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.

The relation between apolipoprotein E (APOE) genotype and peripheral artery disease in patients at high risk for cardiovascular disease

2016 ◽  
Vol 246 ◽  
pp. 187-192 ◽  
Author(s):  
Charlotte Koopal ◽  
Mirjam I. Geerlings ◽  
Majon Muller ◽  
G.J. de Borst ◽  
Ale Algra ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Apolipoprotein E ◽  
Peripheral Artery Disease ◽  
Apoe Genotype ◽  
Peripheral Artery ◽  
Artery Disease

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.

Lipid-lowering therapies in peripheral artery disease: A review

2020 ◽  
pp. 1358863X2095709
Author(s):  
Nedaa Skeik ◽  
Meagan E Nowariak ◽  
Jenna E Smith ◽  
Jason Q Alexander ◽  
Jesse M Manunga ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Extensive Literature ◽  
Lipid Lowering Therapy ◽  
Current Guideline ◽  
Peripheral Artery ◽  
Pcsk9 Inhibitors ◽  
Risk Factor Modification ◽  
The Us ◽  
Artery Disease

Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, PAD patients are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.

scholarly journals Efficacy and Safety of Vorapaxar by Intensity of Background Lipid‐Lowering Therapy in Patients With Peripheral Artery Disease: Insights From the TRA2P‐TIMI 50 Trial

2021 ◽  
Author(s):  
Ian C. Gilchrist ◽  
David A. Morrow ◽  
Mark A. Creager ◽  
Jeffrey W. Olin ◽  
Benjamin M. Scirica ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Peripheral Artery Disease ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Artery Disease ◽  
Ischemic Events ◽  
Statin Use

Background Patients with peripheral artery disease are at increased risk of both major adverse cardiovascular events (MACEs) and limb events. The pathobiology of limb events is likely multifactorial. Observational studies suggest a benefit of statin therapy for reducing the risk of limb ischemic events while randomized trials demonstrate a benefit with more potent antithrombotic therapies, particularly those targeting thrombin. Whether the effects of these therapeutic pathways are independent and complementary is not known. Methods and Results The TRA 2°P‐TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–Thrombolysis in Myocardial Infarction 50) trial demonstrated that vorapaxar significantly reduced MACEs and limb events. The purpose of the current analysis was to evaluate the association of statin use and intensity and the occurrence of MACEs and limb events in 5845 patients with symptomatic peripheral artery disease randomized in TRA 2°P‐TIMI 50 and then to understand whether statin use modified the benefits of vorapaxar for MACEs or limb ischemic events. We found that statin therapy was associated with significantly lower risk of MACEs (hazard ratio [HR], 0.77; 95% CI, 0.66–0.89; P <0.001) and limb ischemic events (HR, 0.73; 95% CI, 0.60–0.89; P =0.002). The benefit of vorapaxar for reducing MACEs and limb events was consistent regardless of background statin ( P ‐interaction=0.715 and 0.073, respectively). Event rates were lowest in patients receiving the combination of statin therapy and vorapaxar. Conclusions In conclusion, statin use and intensity is associated with significantly lower rates of MACEs and limb ischemic events. Thrombin inhibition with vorapaxar is effective regardless of background statin therapy. These results suggest that targeting both lipid and thrombotic risk in peripheral artery disease is necessary in order to optimize outcomes.

A systematic review and meta-analysis of the role of statins and their intensity in peripheral artery disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Sagris ◽  
J Katsaros ◽  
S Giannopoulos ◽  
DG Kokkinidis
Keyword(s):  
Systematic Review ◽  
Peripheral Artery Disease ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Free Survival ◽  
Low Intensity ◽  
All Cause Mortality ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Peripheral artery disease (PAD) affects more than eight million Americans. However, several studies have shown that those patients are often undertreated, and that statin utilization is suboptimal.  American Heart Association guidelines highlight statins as the first-line lipid-lowering therapy to treat patients with PAD. Our objective with this meta-analysis was to further explore the impact of statins on PAD outcomes and examine whether the actual statin (high vs low intensity) dose impacts outcomes. Methods We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented a comparison of statins vs no statins for PAD patients or compared high vs low intensity statins and provided outcomes with hazard ratio was considered as potentially eligible. The Medline (PubMed) database was searched up to August 30, 2020. A random effects meta-analysis was performed. Results In total, 38 studies and 275,670 patients were included in this meta-analysis. In total, 136,025 (49.34%) were on statins vs 139,645 (50.66%) who were not on statins. Statins had an association with a reduction in all cause-mortality by 42% (HR:0.58, 95% CI: 0.49-0.67, I2= 96.26%) and cardiovascular death by 43% (HR:0.57, 95% CI: 0.40-0.74, I2= 80.39%). Statins use was associated with an increase in amputation-free survival by 56% (HR:0.44, 95% CI: 0.30-0.58, I2 = 15%). The risk of amputation and loss of patency was reduced by 35% (HR:0.65, 95% CI:0.41-0.89, I2 = 86.91%), 46% (HR:0.54, 95% CI: 0.34-0.74, Ι2 = 0%), respectively. Statins use was also associated with a reduction in the risk of major adverse cardiovascular events (MACE) by 35% (HR:0.65, 95% CI: 0.51-0.80, I2= 93.22%) and the incidence of myocardial infarction (MI) by 41% (HR:0.59, 95% CI: 0.33-0.86, I2 = 76.78%). Among patients treated with statins, high-intensity treatment group was associated with a reduction in all cause-mortality by 36% (HR:0.64, 95% CI: 0.54-0.74, I2 = 96.49%) compared to patients treated with low intensity statins. Conclusion Statin treatment among patients with PAD was associated with a statistically significant reduction in all-cause mortality, cardiovascular mortality, MI, MACE, risk for amputation or loss of patency. Statins were also associated with a higher amputation free survival.

scholarly journals Prediction of basal glycaemia dynamics during treatment with 6-month lipid-lowering therapy in patients at high risk of cardiovascular disease

2017 ◽  
Vol 20 (5) ◽  
pp. 374-383
Author(s):  
Olga A. Koshelskaya ◽  
Anastasiya S. Sushkova ◽  
Olga A. Zhuravleva ◽  
Irina V. Vinnizkaya ◽  
Nataliya G. Brazovskaya ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Meta Analysis ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Linear Discriminant ◽  
Glucose Levels ◽  
Lowering Therapy ◽  
Patients With Diabetes

Background. A major meta-analysis has confirmed the ability of statins to exert both diabetogenic and hyperglycaemic effects. To date, practical recommendations for predicting glucose dynamics during lipid-lowering therapy have not been developed. Aims. Identify the combination of factors that can predict changes in basal glycaemia during 6-month lipid-lowering therapy in patients at high risk of cardiovascular disease. Methods. This study reports on 50 patients with diabetes or impaired glucose tolerance, and 18 patients with coronary artery disease without disorders of carbohydrate metabolism. Of note, 29 of the 50 diabetic or glucose intolerant patients had documented ischaemic heart disease (stable angina). Patients were randomised into three groups: Gr.1 (n=33, atorvastatin therapy), Gr.2 (n=17, atorvastatin in combination with ezetimibe) and Gr.3 (n=18, rosuvastatin therapy). After treatment for 24 weeks, we assessed lipid profile dynamics, metabolism of glucose/insulin and the HOMA-IR index. Multivariate analysis was then performed to identify factors that predicted increases in basal glycaemia. Results. All of the included patients completed 24 weeks of treatment (N=68). Lipid-lowering effect was significant in all three groups, and overall, target LDL cholesterol level was achieved in 50% of patients (n=34). In Gr.2, basal glucose level increased from 5.5(5.36.6) to 6.3(5.67.8) mmol/l (p=0.0014), which was accompanied by an increase in HOMA-IR (p=0.024). No significant change in basal glycaemia was observed in Grs.1 and 3. Moreover, an increase in the basal glycaemia was observed in 48.5% of patients in Gr.1, 70.6% in Gr.2 and 44.4% in Gr.3. Multivariate discriminant analysis across all patient groups revealed a canonical linear discriminant function that included the following factors: baseline basal glucose levels, total cholesterol levels, triglycerides and ratio of LDL/HDL cholesterol. Sensitivity and specificity of the model accounted for 75%; 51 out of the 68 cases were correctly classified when predicting the dynamics of basal glucose during lipid-lowering therapy. Conclusions. Our data demonstrate the ability to predict the dynamics of the basal glycaemia during lipid-lowering therapy. This may allow for a new way to identify patients at high risk of statin-related increases in glycaemia.

Improved lipid target level attainment in patients with peripheral artery disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Jörn F. Dopheide ◽  
Luise Adam ◽  
Sebastian Wiedmer ◽  
Mathias Kaspar ◽  
Günther Silbernagel ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Prospective Observational Study ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Target Level ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Very High ◽  
Vascular Region

Background: Patients with peripheral artery disease (PAD) fall under the category of a very high cardiovascular risk. Although, consequent lipid lowering therapy (LLT) is advised, only sparse data on attained target level in PAD exists. Objectives: We aimed to analyse contemporary guideline recommendations for LLT in symptomatic PAD patients. Methods: monocentric, prospective, observational study involving 200 symptomatic PAD patients. Guideline target level attainment and LLT were analysed between 2017 and 2019. Results: Overall 78.5% of the patients were on statin therapy, mainly of high intensity with atorvastatin in 50% and rosuvastatin in 33% of the cases. Average statin dosage adjusted for simvastatin was 55 mg/d. Low density lipoproteincholesterol (LDL-C) was <1.8 mmol/L in 53% and <1.4 mmol/L in 34% of the cases. Mean LDL-C levels were at 1.85 ± 0.88 mmol/L. We observed no difference in the treatment and the target level attainment of patients with a stable PAD (intermittent claudication) or chronic critical PAD. However, patients with ≥1 vascular region affected (i.e. coronary and/or cerebrovascular) were treated more intensively and had lower LDL-C levels than patients with PAD alone. Conclusion: It appears that there is more awareness and improvement of previously documented undertreatment of LDL-C levels in symptomatic PAD patients. Although statin treatment is initiated in the majority of patients, our findings call for a continuously intensified LLT in symptomatic PAD patients.

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