Management of type IIb dyslipidemia

Although the Japan Atherosclerosis Society guideline for the diagnosis and prevention of atherosclerosis cardiovascular diseases for the Japanese population provides targets for low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol to prevent cardiovascular disease in patients with dyslipidemia, there is no guideline specifically targeting the treatment of type IIb dyslipidemia, which is one of the most common types of dyslipidemia, along with type IIa and type IV dyslipidemia. Type IIb dyslipidemia is important because it sometimes accompanies atherogenic lipid profiles, such as small, dense LDL, remnants, low HDL cholesterolemia. It is also associated with type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease (CKD), and most patients with familial combined hyperlipidemia (FCHL) show this phenotype; therefore, it is assumed that patients with type IIb dyslipidemia have a high risk for cardiovascular disease. Thus, the management of type IIb dyslipidemia is very important for the prevention of cardiovascular disease, so we have attempted to provide a guideline for the management of type IIb dyslipidemia.     

Eisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology

Eisenmenger syndrome is the most severe and extreme phenotype of pulmonary arterial hypertension associated with congenital heart disease. A large nonrestrictive systemic left-to-right shunt triggers the development of pulmonary vascular disease, progressive pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal. Herein, we review the changing epidemiological patterns and pathophysiology of Eisenmenger syndrome. Multiorgan disease is an integral manifestation of Eisenmenger syndrome and includes involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems. Standardized practical guidelines for the assessment, management, risk stratification, and follow-up of this very fragile and vulnerable population are discussed. Multidisciplinary care is the best clinical practice. An approach to the prevention and management of a broad spectrum of complications is provided. Relevant therapeutic questions are discussed, including anticoagulation, noncardiac surgery, physical activity, transplantation, and advanced-care planning (palliative care). Advanced pulmonary arterial hypertension therapies are indicated in patients with Eisenmenger syndrome and World Health Organization functional class II or higher symptoms to improve functional capacity, quality of life, and—less well documented—survival. Specific recommendations regarding monotherapy or combination therapy are provided according to functional class and clinical response. The ultimate challenge for all care providers remains early detection and management of intracardiac and extracardiac shunts, considering that Eisenmenger syndrome is a preventable condition.     

Management of diabetic dyslipidemia.

Identification and management of dyslipidemia is an important element in the multi-factorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol, predominance of small, dense low-density lipoprotein (LDL) particles, and average LDL cholesterol (LDL-C). Lipid-lowering therapy has a beneficial effect on cardiovascular outcomes. Statin treatment is beneficial in patients who are older than 40 years of age, irrespective of the LDL-C value. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions, such as diet, exercise, smoking cessation, weight loss, and improving glycemic control. Although statin therapy is recommended for most subjects, judicious use of combination therapy should be considered in the highest risk subjects.     

Raising low levels of high-density lipoprotein cholesterol is an important target of therapy

Recent clinical trials in patients with coronary heart disease indicate, for the very first time, that increasing low levels of high-density lipoprotein (HDL) cholesterol significantly reduces the cumulative occurrence of cardiovascular and cerebrovascular events in patients whose only lipid abnormality was low HDL with normal levels of low-density lipoprotein (LDL) cholesterol and triglycerides. These data provide a compelling scientific basis for a more targeted and segmental approach to managing patients with dyslipidemia, where decreasing elevated levels of LDL cholesterol and increasing low levels of HDL cholesterol should comprise dual targets of pharmacotherapy.     

Emerging importance of HDL cholesterol in developing high-risk coronary plaques in acute coronary syndromes

Cardiovascular disease is the principal cause of death in industrialized countries. Hyperlipidemia, with high low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol levels (<40 mg/dL in men and <45 mg/dL in women), is a known major cardiovascular risk factor. Statins are considered the most potent and effective agents to reduce low-density lipoprotein cholesterol, but they have a variable effect on high-density lipoprotein cholesterol and triglycerides. Different clinical trials with statins have shown a decrease in low-density lipoprotein cholesterol by 35% and a reduction of the incidence of coronary events by as much as 30%. However, 60 to 70% of events still occur, despite remarkable reduction of low-density lipoprotein cholesterol concentration. Recent National Cholesterol Education Program guidelines highlighted the importance of high-density lipoprotein cholesterol concentration in the prevention and treatment of cardiovascular disease. High-density lipoprotein cholesterol is considered an independent risk factor and has an inverse relation with coronary events. The association of low levels of high-density lipoprotein cholesterol with an increased incidence of cardiovascular events implies a critical role of high-density lipoprotein in the protection against atherosclerotic disease and in the progression of coronary atherosclerotic disease. High-density lipoprotein cholesterol appears to exert this protective effect through multiple mechanisms. High-density lipoprotein is not only involved in reverse cholesterol transport, but also prevents endothelial dysfunction; inhibits the homing of monocytes, apoptosis, platelet activation, and factor X activation; and has antioxidant properties. In this article the authors review the available experimental and clinical evidence supporting the importance of high-density lipoprotein cholesterol as a protective factor in coronary artery disease, and the strategies developed to increase high-density lipoprotein cholesterol.     

非高密度脂蛋白胆固醇可以替代低密度脂蛋白胆固醇吗?

非高密度脂蛋白胆固醇(non-HDL-C)等于总胆固醇减去高密度脂蛋白胆固醇.流行病学研究认为,在糖尿病、甘油三酯过高和低密度脂蛋白胆固醇(LDL-C)过低的人群中,non-HDL-C比LDL-C更能反映动脉粥样硬化性心血管疾病的发病风险,预测能力更强.对于动脉粥样硬化性心血管疾病患者,non-HDL-C的目标值已被写...     

The Use of Fibric Acid Derivatives in Cardiovascular Prevention

Clinical trials have demonstrated the benefit of reduction of low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerotic cardiovascular disease. Evidence is less robust for the effect of reduction of triglyceride levels and increase of high-density lipoprotein (HDL) cholesterol levels. In spite of the decrease of cardiovascular events in trials of LDL cholesterol–lowering medications, considerable residual risk remains, even with the use of high-dose statins. The fibric acid derivatives or fibrates reduce triglyceride and increase HDL cholesterol levels, effects that would be expected to affect cardiovascular events. However, clinical outcomes trials with fibrates have shown mixed results. Post-hoc analyses of fibrate trials as well as several meta-analyses suggest an overall decrease in primarily non-fatal coronary events without decrease in total mortality. The effects are most apparent in patients with elevated triglycerides and low HDL cholesterol levels. Statin therapy is the treatment of choice for most patients with dyslipidemia. The addition of a fibrate appears to be most beneficial in high-risk patients who continue to have significant dyslipidemia on statin therapy, most notably patients with diabetes mellitus or the metabolic syndrome. Thus, fibrates are not first-line drugs, but they do have a place in the management of the atherogenic lipid profile.     

Inhibition of cholesteryl ester transfer protein activity: A new therapeutic approach to raising high-density lipoprotein

High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease (ASCVD), leading to the concept that pharmacologic therapy to raise HDL cholesterol levels may reduce ASCVD risk. There is substantial interest in the concept of inhibition of the cholesteryl ester transfer protein (CETP) as a novel strategy for raising HDL cholesterol levels, as well as reducing levels of atherogenic lipoproteins. This article reviews the physiology of CETP in lipoprotein metabolism and the data in animals and humans that are relevant to the question of whether CETP inhibition may some day be part of the clinical armamentarium for treating dyslipidemia and atherosclerotic vascular disease.     

代谢综合征血脂异常的特点及治疗研究进展

代谢综合征具有多种心血管疾病的危险因素。其核心成分之一血脂异常易致动脉粥样硬化,主要有高三酰甘油、低高密度脂蛋白胆固醇和小而密低密度脂蛋白胆固醇升高。降脂治疗的基本措施是改善生活方式,药物治疗包括他汀类、贝特类、烟酸、依折麦布、胆固醇酯转运蛋白抑制剂等及联合治疗。     

Low high-density lipoprotein cholesterol disorders and cardiovascular risk: contribution of associated low-density lipoprotein subclass abnormalities

PURPOSE OF REVIEW: Discuss the contribution of low-density lipoprotein subclass abnormalities to cardiovascular risk among individuals with low high-density lipoprotein cholesterol levels. RECENT FINDINGS: Low high-density lipoprotein cholesterol levels are commonly encountered among patients with early onset cardiovascular disease. Most often, a low high-density lipoprotein cholesterol level is not an isolated abnormality, but it is usually associated with a number of other lipoprotein abnormalities. Data from the Framingham Offspring Study demonstrate that among subjects with high-density lipoprotein cholesterol, 1.0 mmol/L (39 mg/dL), low-density lipoprotein particle numbers were considerably higher than indicated by the level of low-density lipoprotein cholesterol because these subjects had excess numbers of small cholesterol-depleted low-density lipoprotein particles. Elevated numbers of low-density lipoprotein particles identify individuals at highest risk for atherosclerotic vascular disease and cardiovascular events. SUMMARY: As high levels of low-density lipoprotein particles are a robust predictor of cardiovascular events, strategies targeted at raising low levels of high-density lipoprotein cholesterol must account for low-density lipoprotein particle interactions.     

New approaches in the intensive management of cardiovascular risk in the metabolic syndrome

When risk factors such as dyslipidemia and hypertension are inadequately controlled in subjects with the metabolic syndrome by lifestyle interventions, pharmacologic approaches are warranted. Statins are first-line pharmacotherapy for dyslipidemia due to their efficacy for lowering low-density lipoprotein (LDL) cholesterol and may also improve high-density lipoprotein (HDL) cholesterol and triglyceride levels. Fibrates and niacin may be useful in combination with a statin for additionally lowering triglycerides or raising HDL cholesterol. Adequate control of hypertension will usually require two or more drugs; agents that block the renin-angiotensin system are particularly useful in this population, given their demonstrated benefits for reducing the burden of cardiovascular events and end-stage renal disease independent of blood-pressure lowering. A multifaceted approach to risk factor management for the metabolic syndrome will have benefits for prevention of type 2 diabetes and cardiovascular disease.     

Dyslipoprotein?mie und k?rperliche Aktivit?t

Cardiovascular disease is a major health problem in developed countries. A sedentary lifestyle and unhealthy diet increase cardiovascular risk factors, such as dyslipidemia, hypertension and insulin resistance. Life style modification is strongly recommended for prevention and therapy of cardiometabolic diseases and dyslipidemia. Regular physical activity can positively influence the lipoprotein profile by reducing triglycerides and increasing high-density lipoprotein cholesterol (HDL-C). Exercise seems to have little effect on total cholesterol and low-density lipoprotein cholesterol (LDL-C) but improves LDL subfractions by reducing small dense -LDL particles and increases the average size of LDL particles. The beneficial effect of physical activity on the lipoprotein profile seems to be more dependent on the amount of exercise than on the intensity. High-intensity training seems to have less effect than moderate aerobic exercise training on lipoproteins but is superior or equal in improving other metabolic risk factors.     

Dyslipidemia in patients with nonalcoholic fatty liver disease

Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein particles and dysregulated clearance of lipoproteins from the circulation. There is unequivocal evidence that cardiovascular disease is the most common cause of mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a critical role in the overall management of patients with NAFLD. Statins are the first-line agents to treat high cholesterol and their dosage should be adjusted based on achieving therapeutic targets and tolerability. Although all statins appear to be effective in improving cholesterol levels in patients with NAFLD, there is more experience with atorvastatin in patients with NAFLD; furthermore, it is the only statin to date to show a reduced cardiovascular morbidity in patients with NAFLD. The risk for serious liver injury from statins is quite rare and patients with NAFLD are not at increased risk for statin hepatotoxicity. Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia because of their safety, tolerability, and efficacy in improving serum triglycerides, as well as their potential to improve liver disease.     

Novel Biomarkers for Predicting Cardiovascular Disease in Patients With Diabetes

It is generally acknowledged that patients with diabetes comprise a high-risk population for the development of cardiovascular disease. However, it is perhaps less well recognized that there actually exists considerable heterogeneity in vascular risk within this patient population, with a sizable subset of individuals seemingly at low risk for major cardiovascular events despite the presence of diabetes. Because traditional clinical risk calculators have shown wide variability in their performance in the setting of diabetes, there exists a need for additional risk predictors in this patient population. In this context, there has been considerable interest in the potential utility of circulating biomarkers as clinical tools that might facilitate risk stratification and thereby guide therapeutic and preventative decision-making. Coupled with the current era of dedicated cardiovascular outcome trials in type 2 diabetes, this interest has spawned a growing literature of recent studies that evaluated potential biomarkers. To date, these studies have identified N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponins, and growth differentiation factor-15 as cardiovascular biomarkers of particular potential in patients with diabetes. Furthermore, recognizing the potential benefit of collective consideration of different biomarkers reflecting distinct pathophysiologic processes that might contribute to the development of cardiovascular disease, there is emerging emphasis on the evaluation of combinations of biomarkers for optimal risk prediction. Although not currently ready for clinical practice, this rapidly-growing topic of biomarker research might ultimately facilitate the goal of individualized risk stratification and thereby enable truly personalized management of diabetes.     

Combination therapy of dyslipidemia

Clinical trials have demonstrated the benefit of low-density lipoprotein (LDL) cholesterol reduction and, with less robust evidence, reduction of triglyceride levels and increased high-density lipoprotein (HDL) cholesterol in the prevention of atherosclerotic cardiovascular disease. Although the statins are the cornerstone of lipid-lowering therapy, they may not be adequate to accomplish all of the changes in lipid and lipoprotein levels called for in current guidelines. Combinations of one or more lipid-modifying drugs in addition to lifestyle changes are now part of clinical guidelines and are being used extensively in practice. Clinicians need to be familiar with the individual drugs and how they interact. There is also a need for outcome data with combination therapy, especially for statin-fibrate and statin-niacin combinations. Several clinical trials are underway and should provide further evidence for the benefit of combination therapy of dyslipidemia. New drug classes have the potential to provide additive effects with currently available medications to provide substantial LDL reduction and increased HDL level that may lead to a substantial reduction in the burden of atherosclerotic vascular disease.     

Management of dyslipidemia in diabetes

Diabetes is associated with a high risk of cardiovascular disease. The management of dyslipidemia, a well-recognized and modifiable risk factor among patients with type 2 diabetes, is an important element in the multifactorial approach to prevent coronary heart disease. Diabetic dyslipidemia typically consists of elevated triglyceride, low high-density lipoprotein cholesterol (HDL-C), and the predominance of small dense low-density lipoprotein (LDL) particles. LDL cholesterol (LDL-C) levels in patients with diabetes are similar to those found in the rest of the population. During the past few years, clinical trials have provided evidence that lipid-lowering therapy has a similar beneficial effect on cardiovascular outcomes in diabetic and nondiabetic individuals. According to current guidelines, the primary lipid target is an LDL-C <100 mg/dL (<70 mg/dL in very high-risk patients) and, to this end, statins are the agents of choice. The appropriate management of dyslipidemia in patients with diabetes, particularly in individuals with low LDL-C, remains controversial. To achieve lipid targets, attention should be directed first toward nonpharmacologic therapeutic interventions to control dyslipidemia, such as diet, exercise, smoking cessation, weight loss, and glycemic control. Statin therapy is recommended for most subjects but, frequently, a combination of lipid-lowering agents is required. A number of combinations are possible, and several factors should be considered to improve the safety of this strategy.     

Treatment goals for the management of lipids and inflammation for patients with coronary artery disease

Opinion statement Appropriate management of lipids is a central component of risk reduction in patients with coronary artery disease (CAD). According to the most recent guidelines, low-density lipoprotein cholesterol (LDLC) is the principal target of lipid-lowering therapy and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the mainstay of this therapy. The actual target level of LDL lowering is being reassessed in light of recent clinical trials. Once appropriate LDL lowering has been achieved, treatment of other targets such as high-density lipoprotein cholesterol (HDLC), triglycerides, and non-HDLC should be considered. In addition to dyslipidemia, multiple observational studies suggest that inflammatory markers such as C-reactive protein (CRP) are associated with risk of cardiovascular events and that treatment with statins may lower CRP levels. However, there are insufficient data at this time supporting treatment of CRP as a principal target in CAD.     

Approach to Lipid Therapy in the Patient With Atherosclerotic Vascular Disease

Hyperlipidemia increases the incidence of atherosclerotic vascular disease and is associated with greater rates of recurrent cardiovascular events among individuals with established vascular disease. Several large population studies have confirmed the link between all cholesterol components (including elevated low-density lipoprotein [LDL] cholesterol, total cholesterol, and triglyceride levels, and reduced high-density lipoprotein [HDL] levels) with coronary heart disease and other manifestations of systemic atherosclerosis. In addition, landmark clinical trials have clearly established that lowering LDL cholesterol levels with statins (HMG-CoA reductase inhibitors) can lower recurrent cardiovascular events by nearly 25%. The benefits of altering non-LDL cholesterol levels (eg, triglycerides and HDL) are less clear, but several other medications are often used in conjunction with statins for cholesterol lowering. First-line therapy for lipid lowering in patients with atherosclerotic vascular disease includes statins and a recommendation for lifestyle changes (including diet and exercise). Second-line options for lowering cholesterol include fibrates, nicotinic acid, bile acid sequestrants, and ezetimibe. Therapeutic goals for patients with vascular disease are to achieve an LDL cholesterol level < 100 mg/dL, or <70 mg/dL in individuals at particularly high risk.     

Saturated Fatty Acids and Risk of Coronary Heart Disease: Modulation by Replacement Nutrients

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat.