scholarly journals Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Hofit Cohen ◽  
◽  
Claudia Stefanutti
Keyword(s):  
Cardiovascular Disease ◽  
Early Detection ◽  
Children And Adolescents ◽  
Cardiovascular Events ◽  
Current Approach ◽  
Young Age ◽  
New Drugs ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels ◽  
Atherosclerotic Changes

Abstract Purpose of Review To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation

2021 ◽  
pp. 152692482110246
Author(s):  
Grace Hsu ◽  
Tracy M. Sparkes ◽  
Brent N. Reed ◽  
Stormi E. Gale ◽  
Brian E. Crossley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Renal Transplant ◽  
Cardiovascular Events ◽  
Graft Failure ◽  
Deceased Donor ◽  
Low Risk ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease

Introduction: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. Research question: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. Design: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. Results: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; ( P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. Discussion: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

Abstract P019: A Single Model For Predicting Major Adverse Cardiovascular Events In Individuals With And Without History Of Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk In Communities (aric) Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Yejin Mok ◽  
Lena Mathews ◽  
Ron C Hoogeveen ◽  
Michael J Blaha ◽  
Christie M Ballantyne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Risk Stratification ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Single Model ◽  
History Of ◽  
Very High

Background: In the 2018 AHA/ACC Cholesterol guideline, risk stratification is an essential element. The use of a Pooled Cohort Equation (PCE) is recommended for individuals without atherosclerotic cardiovascular disease (ASCVD), and the new dichotomous classification of very high-risk vs. high-risk has been introduced for patients with ASCVD. These distinct risk stratification systems mainly rely on traditional risk factors, raising the possibility that a single model can predict major adverse cardiovascular events (MACEs) in persons with and without ASCVD. Methods: We studied 11,335 ARIC participants with (n=885) and without (n=10,450) a history of ASCVD (myocardial infarction, ischemic stroke, and symptomatic peripheral artery disease) at baseline (1996-98). We modeled factors in the PCE and the new classification for ASCVD patients (Figure legend) in a single CVD prediction model. We examined their associations with MACEs (myocardial infarction, stroke, and heart failure) using Cox models and evaluated the discrimination and calibration for a single model including those factors. Results: During a median follow-up of 18.4 years, there were 3,658 MACEs (3,105 in participants without ASCVD). In general, the factors in the PCE and the risk classification system for ASCVD patients were associated similarly with MACEs regardless of baseline ASCVD status, although age and systolic blood pressure showed significant interactions. A single model with these predictors and the relevant interaction terms showed good calibration and discrimination for those with and without ASCVD (c-statistic=0.729 and 0.704, respectively) (Figure). Conclusion: A single CVD prediction model performed well in persons with and without ASCVD. This approach will provide a specific predicted risk to ASCVD patients (instead of dichotomy of very high vs. high risk) and eliminate a practice gap between primary vs. secondary prevention due to different risk prediction tools.

Cardiovascular Prognosis in Drug-Resistant Hypertension Stratified by 24-Hour Ambulatory Blood Pressure: The JAMP Study

Hypertension ◽  
2021 ◽  
Author(s):  
Kazuomi Kario ◽  
Satoshi Hoshide ◽  
Keisuke Narita ◽  
Yukie Okawara ◽  
Hiroshi Kanegae ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Ambulatory Blood Pressure ◽  
Resistant Hypertension ◽  
Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Artery Disease

Resistant hypertension is an important cardiovascular risk factor. This analysis of the JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) data investigated the effects of uncontrolled resistant hypertension diagnosed using ambulatory blood pressure (BP) monitoring on the risk of heart failure (HF) and overall cardiovascular events. The JAMP study patients with hypertension and no HF history were included. They had true resistant hypertension (24-hour BP ≥130/80 mm Hg), pseudoresistant hypertension (24-hour BP <130/80 mm Hg), well-controlled nonresistant hypertension (24-hour BP <130/80 mm Hg), or uncontrolled nonresistant hypertension (24-hour BP ≥130/80 mm Hg). The primary end point was total cardiovascular events, including atherosclerotic cardiovascular disease (fatal/nonfatal stroke and fatal/nonfatal coronary artery disease), and HF. During 4.5±2.4 years of follow-up the overall incidence per 1000 person-years was 10.1 for total cardiovascular disease, 4.1 for stroke, 3.5 for coronary artery disease, and 2.6 for HF. The adjusted risk of total cardiovascular and HF events was significantly increased in patients with true resistant versus controlled nonresistant hypertension (hazard ratio, 1.66 [95% CI, 1.12–2.48]; P =0.012 and 2.24 [95% CI, 1.17–4.30]; P =0.015, respectively) and versus uncontrolled nonresistant hypertension (1.51 [1.03–2.20]; P =0.034 and 3.03 [1.58–5.83]; P <0.001, respectively). The findings were robust in a sensitivity analysis using a slightly different definition of resistant hypertension. True resistant hypertension diagnosed using ambulatory BP monitoring is a significant independent risk factor for cardiovascular disease events, especially for HF. This highlights the importance of diagnosing and effectively treating resistant hypertension. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000020377.

Dyslipidaemia

2019 ◽  
pp. 33-48
Author(s):  
Heinz Drexel
Keyword(s):  
Cardiovascular Disease ◽  
Randomized Clinical Trials ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

scholarly journals Whole grains protect against atherosclerotic cardiovascular disease

2003 ◽  
Vol 62 (1) ◽  
pp. 135-142 ◽  
Author(s):  
James W. Anderson
Keyword(s):  
Cardiovascular Disease ◽  
Vascular Reactivity ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Whole Grains ◽  
Atherosclerotic Cardiovascular Disease ◽  
Protective Effects ◽  
Whole Grain ◽  
Cholesterol Levels ◽  
Diabetes And Obesity

Atherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in most Western countries. Nutrition factors contribute importantly to this high risk for ASCVD. Favourable alterations in diet can reduce six of the nine major risk factors for ASCVD, i.e. high serum LDL-cholesterol levels, high fasting serum triacylglycerol levels, low HDL-cholesterol levels, hypertension, diabetes and obesity. Wholegrain foods may be one the healthiest choices individuals can make to lower the risk for ASCVD. Epidemiological studies indicate that individuals with higher levels (in the highest quintile) of whole-grain intake have a 29% lower risk for ASCVD than individuals with lower levels (lowest quintile) of whole-grain intake. It is of interest that neither the highest levels of cereal fibre nor the highest levels of refined cereals provide appreciable protection against ASCVD. Generous intake of whole grains also provides protection from development of diabetes and obesity. Diets rich in whole-grain foods tend to decrease serum LDL-cholesterol and triacylglycerol levels as well as blood pressure while increasing serum HDL-cholesterol levels. Whole-grain intake may also favourably alter antioxidant status, serum homocysteine levels, vascular reactivity and the inflammatory state. Whole-grain components that appear to make major contributions to these protective effects are: dietary fibre; vitamins; minerals; antioxidants; phytosterols; other phytochemicals. Three servings of whole grains daily are recommended to provide these health benefits.

Sign in / Sign up

Export Citation Format

Share Document