- Record: found
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Lipoprotein (a) interactions with cholesterol-containing lipids on angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion
research-article
Author(s):
Ying Shen
1 ,
Shuai Chen
2 ,
Yang Dai
2 ,
Xiao Qun Wang
1 ,
Rui Yan Zhang
1 ,
Zhen Kun Yang
1 ,
Jian Hu
1 ,
Lin Lu
1
,
2 ,
Feng Hua Ding
1
,
,
Wei Feng Shen
1
,
2
,
Publication date (Electronic):
24 June 2019
Journal:
Cardiovascular Diabetology
Publisher:
BioMed Central
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Abstract
Background
We investigated whether or to what extent the interaction of lipoprotein (a) [Lp(a)] with cholesterol-containing lipids was associated with angiographic coronary collateralization in type 2 diabetic patients with chronic total occlusion.
Methods
Serum levels of Lp(a), total cholesterol, low-density lipoprotein–cholesterol (LDL-C), high-density lipoprotein–cholesterol (HDL-C), and triglyceride were determined and non-HDL-C was calculated in 706 type 2 diabetic and 578 non-diabetic patients with stable coronary artery disease and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3).
Results
For diabetic and non-diabetic patients, Lp(a), total cholesterol, LDL-C, and non-HDL-C levels were higher in patients with poor coronary collateralization than in those with good collateralization, whereas HDL-C and triglyceride levels were similar. After adjustment for potential confounding factors, tertiles of Lp(a), total cholesterol, LDL-C and non-HDL-C remained independent determinants for poor collateralization. A significant interaction between Lp(a) and total cholesterol, LDL-C or non-HDL-C was observed in diabetic patients (all P interaction < 0.001) but not in non-diabetics. At high tertile of total cholesterol (≥ 5.35 mmol/L), LDL-C (≥ 3.36 mmol/L) and non-HDL-C (≥ 4.38 mmol/L), diabetic patients with high tertile of Lp(a) (≥ 30.23 mg/dL) had an increased risk of poor collateralization compared with those with low tertile of Lp(a) (< 12.66 mg/dL) (adjusted OR = 4.300, 3.970 and 4.386, respectively, all P < 0.001).
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Most cited references50
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- Abstract: found
- Article: found
2016 Chinese guidelines for the management of dyslipidemia in adults
(2018)
1 Introduction Over the last 30 years, the blood lipid level in the Chinese population has gradually increased, and the incidence of dyslipidemia has significantly increased. A nationwide survey in 2012 showed that the average serum total cholesterol (TC) value in adults was 4.50 mmol/L and that the prevalence of hypercholesterolemia was 4.9%; the average value of triglyceride (TG) was 1.38 mmol/L, and the prevalence of hypertriglyceridemia was 13.1%; the average value of high-density lipoprotein cholesterol (HDL-C) was 1.19 mmol/L, and the prevalence of HDL-C hypolipidemia was 33.9%.[1] The overall prevalence of dyslipidemia among Chinese adults reached 40.4%, which has substantially increased since 2002. The increase of serum cholesterol level in the population will increase by approximately 9.2 million cases of cardiovascular events in China between 2010 and 2030.[2] The prevalence of hypercholesterolemia among Chinese children and adolescents is also significantly increasing,[3] suggesting that the development of dyslipidemia and the relevant disease burdens in Chinese adults will continue to increase. Dyslipidemia characterized by the increase of low-density lipoprotein cholesterol (LDL-C) or TC is an important risk factor for atherosclerotic cardiovascular diseases. The reduction of LDL-C levels can significantly decrease the development and mortality risks of atherosclerotic cardiovascular diseases.[4] Other types of dyslipidemia (e.g., increases of TG or decreases of HDL-C) are also correlated with the increase of developing atherosclerotic cardiovascular diseases.[5]–[7] The effective control of dyslipidemia has important significance for the management of atherosclerotic cardiovascular diseases in China. Encouraging people to adopt a healthy lifestyle is the basic strategy for managing dyslipidemia and atherosclerotic cardiovascular diseases. The focus of dyslipidemia management is to increase the awareness, treatment, and control rates of dyslipidemia. Although the awareness and treatment rates of Chinese adult dyslipidemia patients have increased over recent years,[8] they remain at low levels. Therefore, the management work of dyslipidemia urgently needs to be strengthened. In 2007, a joint committee of multidisciplinary experts together formulated the “Chinese Guidelines for the Management of Dyslipidemia in Adults” (referred to as "Guidelines" hereafter). Based on the full adoption of epidemiological and clinical study results from the Chinese population and combined with international study results and guideline recommendations, the “Guidelines” proposed recommendations that were more appropriate for the management of dyslipidemia in the Chinese population. These recommendations had important guiding functions for the management of dyslipidemia in China.[9] Since 2007, more clinical study results have further validated the effectiveness and safety of cholesterol-lowering treatments on the primary and secondary prevention of atherosclerotic cardiovascular diseases. Many international academic institutions successively updated or formulated new management guidelines for dyslipidemia. During this period, studies in the clinical blood lipid field in China made significant progress. Prospective cohort studies on the Chinese population obtained new 20-year follow-up data. Based on the 10-year overall risk assessment program recommended by the 2007 Guidelines, the lifetime risk assessment program was proposed.[10] In November 2013, supported by the Department of Diseases Control of the National Health and Family Planning Commission of the People's Republic of China (NHFPC), the National Expert Committee on Cardiovascular Diseases of the National Center for Cardiovascular Diseases, the Chinese Society of Cardiology of Chinese Medical Association, the Chinese Diabetes Society of the Chinese Medical Association, the Chinese Society of Endocrinology of the Chinese Medical Association, and the Chinese Society of Laboratory Medicine of the Chinese Medical Association formed a joint committee to revise the blood lipid guidelines. These committee members extensively collected core issues to be addressed by the new guidelines. After discussion, 17 core issues across 4 aspects (the overall principle of guideline revisions, the overall cardiovascular risk assessment, the goals of lipid-lowering treatment, and lipid-lowering treatments for special populations) were eventually confirmed. The guideline-revision working group targeted these core issues to formulate specific literature retrieval and evaluation strategies as well as comprehensively evaluate and screen the relevant literature. The literature retrieval databases included the Chinese Biomedicine Literature Database (CBM), Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CKNI), the American Biomedical Literature Database (PubMed), and the Dutch Excerpta Medica database (EMBASE). In addition, new data from long-term cohort studies in China were used to conduct targeted analyses. The recommendations and suggestions proposed by the revised guidelines were developed after repeated discussion among multidisciplinary experts based on a systemic assessment. When the expert opinions disagreed, the consensus of the majority of experts was accepted based on a full consideration of the different opinions. The guideline revision referenced the standard procedures developed by the World Health Organization (WHO) and the Chinese Medical Association's clinical guidelines.[11] During the process of guideline revision, the National Center for Cardiovascular Diseases raised funds to avoid conflicts of interest with vendors. The definitions of the recommendation classifications in the “Guidelines” reference the definitions in the relevant European and American blood lipid guidelines.[12],[13] The specific descriptions are shown below: Class I: Manipulations or treatments that have been confirmed/unanimously recognized as beneficial, useful, and effective are recommended. Class II: Manipulations or treatments that still have contradictions or different opinions according to useful/effective evidence. Class IIa: Relevant evidence/opinions tend to be useful/effective. The application of these manipulations or treatments is reasonable. Class IIb: Relevant evidence/opinions cannot be fully confirmed as useful/effective. Its application can be considered. Class III: It has been confirmed/consistently recognized as useless/ineffective and manipulations or treatments might be harmful in some cases. Its application is not recommended. The definitions of the level of evidence in the “Guidelines” are described below: Evidence level A: Evidence based on many randomized clinical trials or meta-analyses. Evidence level B: Evidence based on single randomized clinical trials or many non-randomized controlled studies. Evidence level C: Only expert consensus opinion or based on the results of small-scale studies, retrospective studies, or registry studies. 2 Blood lipids and lipoproteins Highlights: Blood lipids are the collective term for cholesterol, TG, and lipoids (e.g., phospholipids) in the serum. Blood lipids that have a close clinical association are primarily cholesterol and TG. Cholesterol in the human body primarily exists in the forms of free cholesterol and cholesteryl ester. TG is formed by the fatty acid esterification of the three hydroxyl groups in the glycerol molecule. Blood lipids are insoluble in water, and they can be dissolved in water after binding to special proteins, lipoproteins (Apo), to form lipoproteins that are transferred to tissues to be metabolized. Lipoproteins are classified as CM, VLDL, IDL, LDL, HDL, and Lp (a). Blood lipids are the collective term for cholesterol, TG, and lipoids (e.g., phospholipids) in serum. Blood lipids that have close clinical association are primarily cholesterol and TG. The blood lipids that have a close clinical association are primarily cholesterol and TG. Cholesterol in the human body primarily exists in the forms of free cholesterol and cholesteryl ester. TG is formed by the fatty acid esterification of the three hydroxyl groups in the glycerol molecule. Blood lipids are insoluble in water, but they can be dissolved in water after binding to special proteins, apolipoproteins (Apo), to form lipoproteins that are transferred to tissues to be metabolized. Lipoproteins are classified as chylomicrons (CM), very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL-C, and HDL-C. One type of lipoprotein is known as lipoprotein (a) (Lp[a]). The physical properties, main components, sources, and functions of lipoproteins are listed in Table 1.[14],[15] Table 1. The characteristics and functions of lipoproteins. Classification Hydration density, g/mL Particle diameter, nm Main component Major apolipoproteins Sources Functions CM 3.4 mmol/L (300 mg/dL), the serum will exhibit emulsion luster until it becomes turbid. 2.3 LDL-C LDL-C is converted from VLDL and IDL (of which TG forms LDL-C after lipase hydrolysis). The LDL-C particle contains approximately 50% cholesterol, and it is the lipoprotein in blood with the highest cholesterol content; therefore, it is called a “cholesterol-rich” lipoprotein. In simple hypercholesterolemia, the increase of the cholesterol concentration parallels the serum LDL-C level. Because LDL-C particles are small even when the concentration of LDL-C is high, the serum will not become turbid. More than 95% of the Apo in LDL-C is Apo B100. Based on particle size and different density levels, LDL-C can be divided into different sub-components. LDL-C transfers cholesterol to the peripheral tissues. Most LDL-C is catabolized by hepatocytes and extrahepatic LDL-C receptors. 2.4 HDL-C HDL-C is primarily synthesized by the liver and small intestine. HDL-C is the smallest particle lipoprotein. Lipid and protein portions almost account for half of the mass. The Apo in HDL-C is primarily Apo A1. HDL-C represents a group of heterogeneous lipoprotein because the quantity and quality of lipids, Apo, enzymes, and lipid transfer proteins in HDL-C particles are different. Using different separation methods, HDL-C can be divided into different sub-components. These HDL-C sub-components have different shapes, densities, particle sizes, electric charges, and anti-atherosclerotic characteristics. HDL-C transfers cholesterol from the peripheral tissues (including atherosclerotic plaques) to the liver for recycling or excretion in the form of cholic acid. This process is called “reverse cholesterol transport”. 2.5 Lp (a) Lp (a) represents a group of special lipoprotein discovered using immunization methods. The lipid components of Lp (a) are similar to those of LDL-C. In addition to one molecule of Apo B100, however, its Apo fraction also contains one molecule of Apo (a). Little is known about the exact mechanisms of Lp (a) synthesis and catabolism. 2.6 Non-HDL-C Non-HDL-C refers to the sum of cholesterol in other lipoproteins except for HDL-C. The calculation formula is non-HDL-C = TC − HDL-C. As a secondary target of lipid-lowering treatment during the management of atherosclerotic cardiovascular disease (ASCVD) and the high-risk population, non-HDL-C is applicable for individuals with LDL-C levels that are not high or have already reached the treatment goal when the TG level is 2.3–5.6 mmol/L (200–500 mg/dL). International blood lipid guidelines recommend using non-HDL-C as the marker for the primary and secondary prevention of ASCVD.[16] 3 Blood lipid examination Highlights: The basic items in clinical blood lipid examination are TC, TG, LDL-C, and HDL-C. The clinical application values of other blood lipid items (e.g., Apo A1, Apo B, and Lp [a]) have also received increasing attention. The basic items in clinical blood lipid detection are TC, TG, LDL-C, and HDL-C. The clinical application values of other blood lipid items (e.g., Apo A1, Apo B, and Lp [a]) have also received increasing attention.[17] 3.1 TC TC refers to the total amount of cholesterol in the various lipids in the blood. The major factors affecting the TC level include the following: (1) Age and gender. TC levels usually increase with age; however, it no longer increases or decreases after 70 years old. The level of TC in young and middle-aged women is lower than that in men. The TC level in women after menopause is higher than that in age-matched men. (2) Eating habits. Long-term high cholesterol and high-saturated fatty acid intake can increase TC. (3) Genetic factors. Mutations in lipoprotein metabolism-related enzymes or receptor genes are the major causes of significant increases in TC. The risk assessment and prediction values of TC on ASCVD are not as accurate as those of LDL-C. The calculation of non-HDL-C and VLDL-C should detect TC. 3.2 TG TG level is affected by the effects of genetic and environmental factors and is associated with race, age, gender, and living habits (e.g., diet and exercise). Unlike TC, TG shows large variations within and between individuals. The TG level in the same individual is influenced by factors such as diet and different time points. Therefore, when the same individual receives multiple detections, the TG values might have significant differences. The serum TG levels in the population show an obvious positive skew. Mild-to-moderate increases in TG usually reflect increases in VLDL and its remnant particles (VLDL with smaller particles). These remnant lipoproteins might directly cause atherosclerosis because the particles become smaller. However, most studies suggest that the increase of TG causes atherosclerosis through the influence of the structures of LDL-C or HDL-C. Survey data indicate that people with mild-to-moderate increases in serum TG levels are at increased risk for the development of coronary heart disease.[18] Severely increased TG is usually accompanied by acute pancreatitis. 3.3 LDL-C Cholesterol accounts for approximately 50% of LDL-C. Therefore, the LDL-C concentration basically reflects the total amount of LDL-C in the blood. The factors that affect TC can also affect the LDL-C level. The increase of LDL-C is a major risk factor for the initiation and progression of atherosclerosis.[12],[16] LDL-C enters into the vascular wall through the vascular endothelia. LDL-C retained in the subcutaneous layer is modified into oxidized-LDL (Ox-LDL). After being phagocytized by macrophages, Ox-LDL forms a foam cell; the latter continues to increase and fuse to become the lipid core of atherosclerotic plaques. Although the pathology of atherosclerosis exhibits chronic inflammatory reaction features, LDL-C might be the basic element for the initiation and maintenance of this chronic inflammatory reaction. Under general conditions, LDL-C parallels TC; however, the TC level is also influenced by the HDL-C level. Therefore, it is better to use LDL-C as the assessment indicator for the risk of ASCVD. 3.4 HDL-C HDL-C can transport cholesterol in peripheral tissues such as the vascular wall to the liver for catabolism (i.e., reverse cholesterol transport). HDL-C can reduce cholesterol deposition in the vascular wall to as an anti-atherosclerosis function. Because the cholesterol content in HDL-C is stable, its current cholesterol content is primarily measured to indirectly understand HDL-C levels in the blood. Genetic factors also significantly influence the level of HDL-C. With the significant reduction of serum TC, people with severe malnutrition have decreased HDL-C. The HDL-C levels of obese people are also lower. Smoking can reduce HDL-C. Diseases such as diabetes, hepatitis, and cirrhosis can be accompanied by low HDL-C; however, exercise and a small amount of alcohol increase HDL-C. Much epidemiological data indicate that serum HDL-C levels are negatively correlated with the incidence of ASCVD.[19] 3.5 Apo A1 The Apo A1 levels in the normal population are primarily within the range of 1.2–1.6 g/L. The levels in women are slightly higher than those in men. The protein component of HDL-C particles (i.e., apolipoprotein) accounts for approximately 50% of its mass. In proteins, Apo A1 accounts for approximately 65%–75%, whereas little Apo A1 is present in other lipoproteins. Therefore, serum Apo A1 reflects the HDL-C level. It is positively correlated with HDL-C levels and has a similar clinical significance. 3.6 Apo B The Apo B levels in the healthy population are primarily within the range of 0.8–1.1 g/L. Under normal conditions, LDL-C, IDL, VLDL, and Lp (a) particles have one molecule of Apo B. Because LDL-C particles account for the majority of these molecules, approximately 90% Apo B is distributed in LDL-C. There are two types of Apo B: Apo B48 and Apo B100. The former is primarily present in CM, whereas the latter is primarily present in LDL-C. Except for special instances, the Apo B routinely measured in clinics usually refers to Apo B100. Serum Apo B primarily reflects the LDL-C level and is positively correlated with the serum LDL-C level. These two types have a similar clinical significance. In a few cases, Apo B hyperlipidemia and normal LDL-C concentrations can occur, suggesting the presence of increased small and dense LDL (sLDL) in the blood. During hypertriglyceridemia (high VLDL), sLDL (LDL pattern B) increases. However, compared with large and light LDL (LDL pattern A), sLDL particles have a high Apo B content and less cholesterol; therefore, this condition when LDL-C is not high but serum Apo B increases is called “Apo B hyperlipidemia”. This situation reflects the increase of LDL pattern B. Therefore, the measurement of ApoB and LDL-C together can help clinical diagnoses. 3.7 Lp (a) Serum Lp (a) concentration is primarily associated with genetics. Gender, age, body weight, and most cholesterol-lowering drugs do not often affect this concentration. The Lp (a) level in the healthy population shows an obvious skew. Although the level in individuals can reach above 1,000 mg/L, the level in 80% healthy individuals is less than 200 mg/L. Usually, 300 mg/L is used as the cutoff point. People with levels higher than this cutoff are at a significantly increased risk for coronary heart disease, suggesting that Lp (a) causes atherosclerosis. However, clinical evidence is lacking.[20] Furthermore, an increase of Lp (a) can also be observed during various acute phase responses, nephrotic syndrome, diabetic nephropathy, pregnancy, and the administration of growth hormone. After all types of stress increase are excluded, Lp (a) is considered as an independent risk factor for ASCVD. The expression unit of the values of all blood lipid measurement items is mmol/L according to the national standard of China. Some other countries use mg/dL. The conversion coefficients are: TC, HDL-C, LDL-C: 1 mg/dL = 0.0259 mmol/L; and TG: 1 mg/dL = 0.0113 mmol/L. 4 Appropriate levels and abnormal cutoff points Highlights: The appropriate levels and abnormal cutoff points of blood lipids are primarily applicable for the target population regarding the primary prevention of ASCVD. The major hazard of dyslipidemia is the increase of the risk for developing ASCVD. The “Guidelines” recommend the appropriate levels and abnormal cutoff points for the blood lipid components in the Chinese population (Table 2) based on the results of many long-term observatory studies concerning the risk of developing ASCVD in Chinese populations with different blood lipid levels, including the independent influence of different blood lipid levels with regard to the cumulative risk for developing ASCVD in the study populations in 10 and 20 years. In addition, the recommendations and the references for the appropriate levels of blood lipid components in the many blood-lipid-related guidelines worldwide are referenced.[12],[16],[21],[22] Importantly, these appropriate levels and abnormal cutoff points of blood lipids are primarily applicable for the target population regarding the primary prevention of ASCVD. Table 2. The appropriate levels and abnormal stratified standards of blood lipids for the primary prevention population of ASCVD in China [mmol/L (mg/dL)]. TC LDL-C HDL-C Non-HDL TG Ideal level 10 mmol/L), and the incidence rate is 1/1000,000. Mild and moderate hypertriglyceridemia are usually associated with multiple gene mutations.[25],[26] 5.2 Clinical classification of dyslipidemia In practice, dyslipidemia can be stratified based on a simple clinical classification (Table 3). Table 3. Clinical classification of dyslipidemia. Type TC TG HDL-C Equal to WHO phenotype Hypercholesterolemia Increase IIa Hypertriglyceridemia Increase IV, I Mixed hyperlipidemia Increase Increase IIb, III, IV, V HDL-C hypolipidemia Decrease LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol; TG: triglyceride; WHO: world health organization. 6 Dyslipidemia screening Highlights: Regular blood lipid examinations are an important measure for managing blood lipid levels and cardiovascular disease. The early detection of individuals with dyslipidemia and the monitoring of their blood lipid level changes are important for the effective implementation of management measures for ASCVD. All MAST institutions in China have the ability to determine blood lipid levels. The detection and monitoring work for patients with dyslipidemia is primarily implemented through routine blood lipid examination in the populations who visit medical institutions. These populations include those who already have ASCVD as well as those who have not developed ASCVD. Health examinations are also an important route to detect dyslipidemia. For the early detection of dyslipidemia, adults between 20–40 years old should receive at least one blood lipid measurement (including TC, LDL-C, HDL-C, and TG) every 5 years. Men older than 40 years of age and postmenopausal women should receive blood lipid measurements every year. Patients with ASCVD and high-risk populations should receive one blood lipid measurement every 3–6 months. Patients who are admitted into hospitals because of ASCVD should receive blood lipid measurements at admission or within 24 h of admission. The key participants for blood lipid examination are (1) people with a history of ASCVD; (2) populations with multiple ASCVD risk factors (e.g., hypertension, diabetes, obesity, and smoking); (3) people with a family history of early-onset cardiovascular diseases (i.e., immediate male family members younger than 55 years old or immediate female family members younger than 65 years old who develop ischemic cardiovascular disease) or patients with familial hyperlipidemia; and (4) people with skin or tendon xanthomas and Achilles tendon thickening. Many factors influence blood lipid detection results. Implementing blood lipid detection should work according to the requirements of the clinical recommendations for determining blood lipids (Supplement 1). 7 Overall cardiovascular risk assessment Highlights: Using different intensities of intervention measures based on the risk of developing ASCVD is the core strategy for the management of dyslipidemia. Overall cardiovascular risk assessment is the basis of dyslipidemia treatment decisions. Overall cardiovascular risk assessment should be performed according to recommended procedures. For people younger than 55 years old, a lifetime risk for cardiovascular disease should be considered. LDL-C or TC levels are independent predictors of the risk of developing ASCVD in individuals and populations.[27]–[29] However, the risk levels of developing ASCVD in individuals are determined not only by the level of cholesterol but also by the number and levels of comorbid risk factors of ASCVD.[29]–[31] Individuals with the same LDL-C level might have significantly different overall risks regarding the development of ASCVD because of the different numbers and levels of other risk factors. More importantly, the overall ASCVD risk is not simply an addition of the cholesterol level and the independent functions of other risk factors; rather, it is the result of the complicated interaction between the cholesterol level and many combined risk factors. Therefore, the same cholesterol level can cause greater harm because of the presence of other risk factors. The comprehensive assessment of the overall risk of ASCVD is a necessary prerequisite for the management of dyslipidemia. The assessment of the overall risk of ASCVD can not only help to confirm the decision of lipid-lowering treatment for patients dyslipidemia but also help clinical physicians make personalized comprehensive treatment decisions targeting multiple risk factors, thereby reducing the overall risk of ASCVD in patients to the greatest degree. Currently, the core content of the dyslipidemia management guidelines released by China and other countries include the assessment methods and risk stratification standards for the overall risk of developing ASCVD.[9],[12],[13],[16],[22],[32]–[35] The 2007 blood lipid guidelines proposed using the risk of development of “ischemic cardiovascular disease” (i.e., coronary heart disease and ischemic stroke) to reflect the comprehensive pathogenic risk of the major risk factors of dyslipidemia and other cardiovascular diseases. For people at moderate risk of developing ASCVD in 10 years who are 3 times of the upper limit of the normal value) was more than 10 times higher than that among European patients, and the risk of myopathy was also 10 times higher. Currently, no safety data exist regarding high-intensity statin therapy in the Chinese population. One feature of the efficacy of lipid-lowering statin drugs is that the initial dose of every statin has excellent lipid-lowering efficacy. When the dose is doubled, LDL-C is further reduced by 6% (the statin efficacy “rule of six”). When the statin dose is doubled, the drug cost proportionally increases, whereas the increase of the efficacy for LDL-C reduction is relative small. Therefore, the use of medium-intensity statins is recommended for initial treatment. The dose is properly adjusted according to individual lipid-lowering efficacy and tolerance conditions. If the cholesterol level does not reach the target, then other lipid-lowering drugs (e.g., ezetimibe) can be used in combination to obtain safe and effective lipid-lowering effects (Class I recommendation, Level B evidence). 8.5 Other dyslipidemia interventions In addition to active cholesterol interventions, whether other dyslipidemia conditions also require treatment lacks the evidence of relevant clinical trial benefits. The appropriate level of serum TG is 20%–30% total energy, especially for high-risk people for ASCVD and other similar conditions. Saturated fatty acid intake should be 4.5 mmol/L (400 mg/day). 10.1.5 Other lipid-lowering drugs Zhibitai is a compound preparation of monascus and traditional Chinese medicine (i.e., hawthorn, alisma, and atractylodes). The most commonly used dose is 0.24–0.48 g twice per day. This compound has mild-to-moderate cholesterol-reducing functions.[85],[86] This drug has few adverse reactions. Policosanol is a mixture containing 8 types of advanced aliphatic alcohol purified from sugarcane wax. The most commonly used dose is 10–20 mg/day. Its lipid-lowering effect is slow, and rare but adverse reactions are known.[87],[88] 10.2 Major TG-lowering drugs Three major TG-lowering drugs exist: fibrates, niacin, and high-purity fish oil preparations. 10.2.1 Fibrates Fibrates reduce serum TG levels and increase HDL-C levels through the activation of peroxisome proliferator activated receptor-α (PPARα) and lipoprotein lipase (LPL).[89]–[93] The most commonly used fibrates include fenofibrate tablets 0.1 g three times per day, micronized fenofibrate 0.2 g once per day, gemfibrozil 0.6 g twice per day, and bezafibrate 0.2 g three times per day. The most common adverse reactions are similar to those of statins, including liver, muscle, and kidney toxicities. The incidence rates of increased serum creatine kinase and ALT levels are both 2.6 mmol/L can also use PCSK9 inhibitors, constituting the combined application of three lipid-lowering drugs with different action mechanisms. 10.4.4 Combined application of statins and n-3 fatty acids The combined application of statins and fish oil preparation n-3 fatty acids can be used to treat mixed hyperlipidemia without increasing adverse reactions. Because taking larger doses of n-3 polyunsaturated fatty acids has a bleeding risk and increases calorie intake in obese patients with diabetes, long-term application is not appropriate. Whether this combination can reduce cardiovascular events is currently under investigation. 11 Other measures for dyslipidemia treatment 11.1 Lipoprotein-plasma exchange Highlights: Lipoprotein-plasma exchange, liver transplantation, partial ileal bypass surgery, and portacaval shunt are used as adjuvant treatment measures for patients with FH. The effect of lipoprotein-plasma exchange has been recognized. Lipoprotein-plasma exchange is an important adjuvant treatment measure for patients with FH,[116] especially for those with HoFH. This treatment can reduce LDL-C levels by 55%–70%. Long-term treatment can cause a reduction of skin xanthomas. The best treatment frequency is once each week. Currently, however, treatments are typically performed once every two weeks. Lipoprotein-plasma exchange can be persistently performed during pregnancy. This treatment measure is expensive, time-consuming, and risks infection. Adverse reactions include hypotension, abdominal pain, nausea, hypocalcemia, iron-deficiency anemia, and allergic reaction. However, with the development of science, technology, and materials, the incidence of relevant adverse reactions has already decreased. 11.2 Liver transplantation and other surgical treatments Liver transplantation can significantly improve LDL-C levels. Although simple liver transplantation or liver transplantation combined with heart transplantation is a successful treatment strategy, many problems exist including many post-transplantation complications, high mortality rates, a lack of donors, and the lifetime administration of immunosuppressive agents. Therefore, this treatment is rarely performed in clinical practice. Although partial ileal bypass surgery and portacaval shunt are not recommended, they should be considered when more effective treatment is lacking for patients with severe HoFH.[116] 12 Management of dyslipidemia in special populations 12.1 Diabetes The major presentations of diabetes combined with dyslipidemia are increased TG, decreased HDL-C, and increased or normal LDL-C.[117] Lipid-lowering treatment can significantly reduce the risk of developing cardiovascular events in patients with diabetes.[61] The target level of LDL-C should be confirmed based on the severity of cardiovascular risks.[118] Patients with diabetes aged 40 years or older should control their serum LDL-C levels below 2.6 mmol/L (100 mg/dL) and maintain their target values of HDL-C above 1.0 mmol/L (40 mg/dL). The principle of dyslipidemia treatment in patients with diabetes follows the ASCVD risk assessment flow chart (Figure 1) for intervention management. According to the features of dyslipidemia, the preferred choice is statin therapy. If patients have combined high TG levels or do not have combined low HDL-C levels, a combination application of statins and fibrates can be used. 12.2 Hypertension For patients with hypertension and dyslipidemia, lipid-lowering treatments should be applied to determine lipid-lowering target values according to different risk levels (Figure 1). Lipid-lowering treatments enable most patients with hypertension to obtain adequate benefits. The results are often more prominent with regard to the reduction of coronary heart disease events.[66] Therefore, the hypertension guidelines recommend that patients with hypertension and medium risk should initiate statin therapy. The newly released HOPE-3 study results suggest that statin therapy significantly reduces cardiovascular events for people at medium risk.[119],[120] For the subgroup population with systolic pressure >143.5 mmHg, the combined application of statins and antihypertensive drugs reduces cardiovascular risks more significantly. 12.3 Metabolic syndrome Metabolic syndrome is a group of clinical conditions that combine the development of obesity, high blood glucose (sugar regulation impairment or diabetes), hypertension, and dyslipidemia (hypertriglyceridemia, HDL-C hypolipidemia, or both). One feature is the combination of interrelated risk factors in the body metabolism of the same individual. These factors directly promote ASCVD development and increase the risk of developing type 2 diabetes. Some evidence indicates that patients with metabolic syndrome are most likely to develop cardiovascular disease. Compared with people without metabolic syndrome, their risks for developing cardiovascular disease and type 2 diabetes are significantly increased. The current cutoff points for determining the hyperglycemia, hypertension, and dyslipidemia aspects of metabolic syndrome were reached via a worldwide consensus. However, the core indicator of metabolic syndrome, obesity (especially central obesity), has different diagnostic criteria. The diagnostic criteria of metabolic syndrome formulated based on study evidence taken from the Chinese population should include three or more of the following items: (1) Central obesity/abdominal obesity: a waist circumference for men of ≥ 90 cm and that for women of ≥ 85 cm; (2) Hyperglycemia: fasting blood glucose ≥ 6.10 mmol/L (110 mg/dL) or 2-h blood glucose after glycemic load ≥ 7.80 mmol/L (140 mg/dL) or patients with confirmed diabetes who have received treatment; (3) Hypertension: blood pressure ≥ 130/85 mmHg or patients with hypertension who have received treatment; (4) Fasting TG ≥ 1.7 mmol/L (150 mg/dL); and (5) Fasting HDL-C 8.5 mmol/L (328 mg/dl), and the serum TC level of HoFH is usually >13.5 mmol/L (521 mg/dl). Left untreated, HeFH patients usually develop cardiovascular disease after 40 years (men) or 50 years (women) of age. HoFH patients typically develop severe cardiovascular disease during childhood, and the mortality rate from cardiovascular diseases in early adulthood is 100 times higher than that among non-FH patients. The ultimate goal of FH treatment is to reduce the risk of ASCVD and decrease the development of fatal and disabling cardiovascular diseases.[116] One focus of treatment is that all patients with FH (including HoFH and HeFH patients) should make enhanced therapeutic lifestyle changes to their diets (i.e., reduce lipid and cholesterol intake and consume a comprehensive balanced diet), exercise, and behavioral habits (i.e., quit smoking and reduce body weight). In addition, the management of other risk factors (e.g., hypertension and diabetes) should be emphasized. Next, patients with FH should adhere to long-term statin therapy beginning in adolescence to significantly reduce the risk of ASCVD. The target level of lipid-lowering treatment is the same as that for people at high cardiovascular risk. LDL-C is reduced by 25% in people with low LDL-C receptors after receiving statin therapy but only by 15% in people without LDL-C receptors. In fact, patients with FH usually require combined treatment with two or more types of lipid-lowering drugs. Patients at very high cardiovascular risk whose cholesterol levels still do not reach target levels after a combined lipid-lowering treatment, especially those with disease in progress, should consider receiving lipoprotein-plasma exchange as an adjuvant therapy. 12.6 Stroke Whether other evidence of combined treatments with atherosclerosis exists, the use of long-term statin therapy for patients with non-cardiogenic ischemic stroke or TIA is recommended to reduce the risk of stroke and cardiovascular events (Class I recommendation, Level A evidence).[63] If the baseline LDL-C level of patients is ≥ 2.6 mmol/L (100 mg/dL), then evidence of the treatment effect of statins is clear; if the baseline level of LDL-C is < 2.6 mmol/L (100 mg/dl), then clinical evidence is lacking. For patients with ischemic stroke resulting from intracranial large atherosclerotic stenosis (stenosis rate: 70%–99%) or patients with TIA, the recommended target value is LDL-C <1.8 mmol/L (70 mg/dL; Class I recommendation, Level B evidence). The long-term administration of statin therapy is safe in general. For patients with non-cardiogenic ischemic stroke and a history of cerebral hemorrhage or patients with TIA, statins can be reasonably used after weighing the risks and benefits. 12.7 Elderly people Elderly people ≥ 80 years old usually have many types of chronic diseases and take various types of drugs. Attention should be paid to the interaction among drugs and their adverse reactions. Most elderly patients have different degrees of liver and kidney dysfunction; therefore, the selection of doses of lipid-lowering drugs should be individualized. The initial dose should not be too high, and the doses of lipid-lowering drugs should be adjusted based on treatment effects; in addition, liver and kidney function and creatine kinase should be closely monitored. Because no randomized controlled studies regarding the target goals of statin therapy have been conducted among elderly patients, there are no special recommendations concerning these patients. Current studies indicate that elderly patients with hypercholesterolemia combined with cardiovascular disease or diabetes benefit from lipid-lowering therapy. Click here for additional data file. Click here for additional data file. Click here for additional data file.
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Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects.
K. Peter Rentrop, Marc Cohen, Heiner Blanke … (1985)
Transluminal coronary angioplasty can serve as a model for controlled coronary artery occlusion and reperfusion which enables assessment of short-term changes in collateral vessel filling in patients with severe atherosclerotic coronary artery disease. In 16 patients with isolated left anterior descending or right coronary artery disease (greater than or equal to 75% stenosis) and normal left ventricular function, collateral filling to the artery being dilated was visualized by contrast injection into the contralateral artery using a second arterial catheter. During balloon inflation, contralateral dye injection was performed as soon as the patient developed angina or ST-T changes or at 90 seconds in those patients without symptoms or signs of ischemia. Grades of collateral filling from the contralateral vessel were: 0 = none; 1 = filling of side branches of the artery to be dilated via collateral channels without visualization of the epicardial segment; 2 = partial filling of the epicardial segment via collateral channels; 3 = complete filling of the epicardial segment of the artery being dilated via collateral channels. At baseline angiography, nine patients had grade 0 collateral filling, seven had grade 1 and none had grade 2 or 3. During coronary occlusion by balloon inflation, collateral filling improved by one grade in eight patients, two grades in five patients, three grades in two patients and remained the same in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus
Jindrich Spinar, Ramon Corbalan, Christopher Cannon … (2018)
Ezetimibe, when added to simvastatin, reduces cardiovascular events after acute coronary syndrome. We explored outcomes stratified by diabetes mellitus (DM).
Author and article information
Contributors
Feng Hua Ding: ruijindfh@126.com
Wei Feng Shen: rjshenweifeng@126.com
Journal
Journal ID (nlm-ta): Cardiovasc Diabetol
Journal ID (iso-abbrev): Cardiovasc Diabetol
Title:
Cardiovascular Diabetology
Publisher:
BioMed Central
(London
)
ISSN
(Electronic):
1475-2840
Publication date
(Electronic):
24
June
2019
Publication date PMC-release: 24
June
2019
Publication date Collection: 2019
Volume: 18
Electronic Location Identifier: 82
Affiliations
Article
Publisher ID: 888DOI: 10.1186/s12933-019-0888-z
PMC ID: 6589890
PubMed ID: 31234867
SO-VID: 8420076d-5144-4f05-85ae-d8bf8ca08b16
Copyright © © The Author(s) 2019
License:
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
History
Date
received
: 21
April
2019
Date
accepted
: 16
June
2019
Funding
Funded by: the Research Foundation of Chinese National Natural Science
Award ID: 81670451
Award ID: 81770437
Award ID: 81770447
Award Recipient
:
Xiao Qun Wang
Feng Hua Ding
Wei Feng Shen
Funded by: Shanghai Science & Technology Committee
Award ID: 14ZR1425800
Award Recipient
:
Ying Shen
Funded by: Medico-engineering Project
Award ID: GY2016MS66
Award Recipient
:
Ying Shen
Funded by: Talent Young Investigators of Shanghai Jiao Tong University School of Medicine
Award ID: 17XJ11009
Award Recipient
:
Ying Shen
Funded by: Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support
Award ID: 20181801
Award Recipient
:
Feng Hua Ding
Categories
Subject:
Original Investigation
Custom metadata
issue-copyright-statement © The Author(s) 2019
ScienceOpen disciplines: Endocrinology & Diabetes
Data availability:
ScienceOpen disciplines: Endocrinology & Diabetes