The lipid triad in type 2 diabetes - prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes.

Cardiovascular disease is the major cause of morbidity and mortality in type 2 diabetes mellitus. Among the established risk factors, the lipid triad (elevated triglycerides, decreased high-density lipoprotein cholesterol, and small dense low-density lipoprotein cholesterol) is a powerful risk factor for atherosclerosis in type 2 diabetes. The prevalence of hypertriglyceridaemia (HTG) in type 2 diabetes is two to three times higher than in non-diabetics. The Copenhagen Male study, the AMORIS study, and several other trials showed hypertriglyceridaemia to be an independent predictor of coronary heart disease (CHD). HTG may promote risk both directly and indirectly through association with alterations of lipoprotein size and composition. The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) demonstrated that raising high-density lipoprotein cholesterol (HDL-C) in patients with low (HDL-C) and low-density lipoprotein cholesterol (LDL-C) is associated with a significant reduction in CHD risk. It was shown in the Diabetes Intervention Study, AFCAPS/TexCAPS, and PROCAM studies that decreased HDL-C and elevated triglycerides are independent risk factors for atherosclerosis, particularly in patients with diabetes mellitus. Several epidemiological studies demonstrated that total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratios or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratios could be better predictors of atherosclerosis than any single lipid parameter. Intima-media thickness (IMT), a well established marker of early atherosclerosis, is associated with HTG/low HDL-cholesterol. In the Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study total and HDL-cholesterol were independent determinants of IMT in subjects at risk for type 2 diabetes. Postprandial HTG was also shown to be correlated with increased IMT in type 2 diabetic patients.     

Residual risk in statin-treated patients: Future therapeutic options

Statin therapy for aggressive low-density lipoprotein cholesterol (LDL-C) reduction reduces cardiovascular morbidity and mortality. However, even on maximal statin therapy, high-risk patients have substantial residual risk of coronary heart disease (CHD). Certain subgroups, such as individuals with diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), metabolic syndrome, or other comorbidities, have a particularly high residual risk. Patients at high risk for future CHD events often require multiple aggressive risk-reduction therapies (eg, antiplatelet agents, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blockade, cholesterol and/or diabetes management, and lifestyle interventions) to further lower their overall cardiovascular risk. For cholesterol management, combination therapy may be required to attain optimal levels of LDL-C, HDL-C, and non-HDL-C.     

What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome?

Patients with type 2 diabetes have an atherogenic lipid profile, which greatly increases their risk of coronary heart disease (CHD) compared with people without diabetes. The largest disparity in lipid levels among people with and without diabetes occurs for high-density lipoprotein cholesterol (HDL-C) and triglycerides: triglycerides tend to be markedly higher and HDL-C moderately lower in patients with diabetes, in contrast to the negligible difference observed in low-density lipoprotein cholesterol (LDL-C) and total cholesterol. However, patients with type 2 diabetes are more likely to have the atherogenic form of LDL-C than people without diabetes, as well as low HDL-C, which restricts reverse cholesterol transport and may also be associated with increased lipid oxidation. Among patients who have suffered a myocardial infarction, increased LDL-C is apparent in early adulthood, whereas a detectable difference in HDL-C levels becomes increasingly apparent with age and most pronounced after age 60 years, compared with healthy controls. Evidence indicates that the increased risk of macrovascular complications of type 2 diabetes begins long before the onset of clinical hyperglycaemia. Despite successful reduction of LDL-C with statin therapy, patients continue to be at increased risk for CHD if their HDL-C levels remain suboptimal, in part due to persistence of enhanced lipid exchange. Observational data suggest that increasing HDL-C should be much more potent therapeutically than a similar proportionate decrease in LDL-C.     

Low HDL-C: a secondary target of dyslipidemia therapy

Current guidelines for the prevention of coronary heart disease (CHD) focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary target of lipid-modifying therapy. However, there is increasing interest in high-density lipoprotein cholesterol (HDL-C) as a secondary target of therapy. A wealth of epidemiologic data demonstrate that low levels of HDL-C are associated with an increased risk of CHD events, and data from large-scale clinical trials with statins and fibrates indicate that observed clinical benefits are related, at least in part, to improvements in HDL-C levels. Raising HDL-C levels with therapeutic lifestyle changes and pharmacologic intervention might afford opportunities to further reduce the risk of CHD beyond LDL-C lowering. Statins are first-line pharmacotherapy for dyslipidemia and can also improve HDL-C levels, although the extent to which they modify HDL-C varies. Combining a fibrate or niacin with statin therapy raises HDL-C more than a statin alone but might be associated with reduced tolerability and increased adverse reactions. Several new therapeutic approaches to raising HDL-C are in development, including an HDL mimetic and inhibitors of cholesteryl ester transfer protein. Although lowering LDL-C remains the primary target of lipid-modifying therapy, dyslipidemia therapies that are efficacious for both LDL-C reduction and raising HDL-C might offer further improvements in CHD risk reduction.     

The effects of oral anti-hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes

Aim:  Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti-hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes.
Methods:  medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p-values and statistical tests.
Results:  Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC.
Conclusions:  Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti-diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.     

Dyslipidaemia in diabetic patients: time for a rethink

Patients with type 2 diabetes have a marked increase in the risk of premature coronary heart disease (CHD). One of the underlying reasons for this increased risk is atherogenic dyslipidaemia, which is common in this patient group and characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-C), increased levels of serum triglycerides, specifically very low-density lipoprotein triglycerides, and an increase in small, dense low-density lipoprotein (LDL) particles. Current management strategies focus on the initial use of statin or fibrate therapy (the latter approach indicated in patients with pronounced hypertriglyceridaemia). Recent treatment guidelines also emphasize the need for reduction in LDL-cholesterol (LDL-C) below 100 mg/dl (2.6 mmol/l) in diabetic patients, as this patient group has a clustering of cardiovascular risk factors that collectively lead to an excess risk of premature mortality. Multidrug lipid-modifying therapy has been proposed to further reduce CHD risk in diabetic patients. Adding nicotinic acid to primary statin therapy would be a logical approach based on the complementary therapeutic benefits of these treatments. Nicotinic acid is the most potent agent currently available for raising HDL-C and is also effective in reducing triglycerides and LDL-C. Moreover, clinical trial data have shown that nicotinic acid can be safely used in diabetic patients. Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study in patients with established CHD and low HDL-C (27% of whom had type 2 diabetes) show the atheroprotective effects of nicotinic acid/statin combination therapy. The clinical benefits of this combination therapy are indicated by subgroup analyses from the HDL-Atherosclerosis Treatment Study, which showed 40% reduction in coronary event frequency in patients with impaired glucose tolerance. Together, these data support the proposed strategy of aggressive multidrug treatment of diabetic dyslipidaemia to improve patient outcome.     

Effect of antihypertensive therapy on serum lipids in newly diagnosed essential hypertensive men

The effect of antihypertensives on serum lipids in newly diagnosed male essential hypertensive patients was studied. The participants (n = 99) were randomly allocated to receive amlodipine, atenolol, enalapril, hydrochlorothiazide, and a combination of amlodipine and atenolol. Lipid parameters were estimated before and after 8 weeks of therapy. The atenolol and thiazide group showed a significant increase in triglycerides (TGs) and very-low-density lipoprotein cholesterol (VLDL-C). High-density lipoprotein cholesterol (HDL-C) and HDL-C to low-density lipoprotein cholesterol (LDL-C) ratio were significantly increased and TC to HDL-C ratio was significantly decreased in the amlodipine and amlodipine- atenolol combination groups. In the enalapril group, we found a significant reduction in TC, TGs, VLDL-C, non-HDL-C, and TG to HDL-C ratio after treatment. It can be concluded from the present study that some drugs have beneficial effects on the lipid status, whereas others adversely affect the lipid status in hypertension.     

Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study)

International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.     

Non-HDL cholesterol as a measure of atherosclerotic risk

Elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, hallmarks of the atherogenic lipid profile found in the metabolic syndrome and type 2 diabetes, are commonly seen in Japanese patients with coronary heart disease (CHD). In the setting of mildly to moderately elevated plasma TG (150-500 mg/dl), very-low-density lipoprotein (VLDL) accumulates and so do high levels of atherogenic TG-rich, cholesterol-enriched remnant particles. Indeed, in hypertriglyceridemia, abnormalities are seen in the quantity and quality of all lipoprotein B-containing lipoproteins. Non-HDL-C (total cholesterol minus HDL-C) provides a convenient measure of the cholesterol content of all atherogenic lipoproteins, and thus incorporates the potential risk conferred by elevated levels of atherogenic TG-rich remnants that is additional to the risk associated with low-density lipoprotein cholesterol (LDL-C). Non-HDL-C level has been found to be a strong predictor of future cardiovascular risk among patients whether or not they exhibit symptoms of vascular disease, and was recently recommended as a secondary treatment target (after LDL-C) in patients with elevated TG by the National Cholesterol Education Program Adult Treatment Panel III. Adoption of this readily available measure to assess risk and response to treatment in patients with elevated TG would improve treatment of dyslipidemia in a substantial number at risk for CHD.     

The triglyceride-high-density lipoprotein axis: an important target of therapy?

Coronary heart disease is the single largest cause of morbidity and mortality in the United States. The link between elevated low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) has been clearly established. However, triglycerides (TG) are increasingly believed to be independently associated with CHD, while high-density lipoprotein cholesterol (HDL-C) is inversely associated with CHD risk. High TG and low HDL often occur together, often with normal levels of LDL-C, and can be described as abnormalities of the TG-HDL axis. This lipid abnormality is a fundamental characteristic of patients with the metabolic syndrome, a condition strongly associated with the development of both type 2 diabetes and CHD. Patients with high TG and low HDL-C should be aggressively treated with therapeutic lifestyle changes. For high-risk patients, lipid-modifying therapy that specifically addresses the TG-HDL axis should also be considered. Current pharmacologic treatment options for such patients include statins, fibrates, niacin, fish oils, and combinations thereof. Several new pharmacologic approaches to treating the TG-HDL axis are currently being investigated. More clinical trial data is needed to test the hypothesis that pharmacologic therapy targeting the TG-HDL axis reduces atherosclerosis and cardiovascular events.     

The role of lipid-lowering therapy in preventing coronary heart disease in patients with type 2 diabetes

Coronary heart disease is the most common cause of death among diabetic patients. The increased risk of coronary heart disease in type 2 diabetes is due, in part, to lipid abnormalities often present in the diabetic patient. Diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C) and an increased preponderance of small, dense low-density lipoprotein cholesterol (LDL-C) particles. Current guidelines for the prevention of coronary heart disease in diabetic patients identify elevated LDL-C as the primary target of lipid-lowering therapy, and recommend statins as the first-line treatment for diabetic dyslipidemia. This review evaluates the large statin trials that have included diabetic patients, and discusses the role of combination therapy in managing dyslipidemia in diabetic patients.     

Does statin monotherapy address the multiple lipid abnormalities in type 2 diabetes?

Lipid abnormalities, which are common in type 2 diabetes, predispose to a greatly increased risk of coronary heart disease. This characteristic dyslipidaemia includes decreased concentrations of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and a small, dense, atherogenic form of low-density lipoprotein cholesterol (LDL-C). Insulin resistance and obesity, which is commonly present in type 2 diabetes, act in concert to disrupt normal lipoprotein metabolism; reverse cholesterol transport in particular. The proatherogenic changes, which result from this process include enrichment of very-low-density lipoprotein with cholesteryl esters and enrichment of LDL with triglycerides. Results from both the Pravastatin Pooling Project and the Heart Protection Study demonstrate that, although people with diabetes obtain the same relative risk reduction with statin therapy, the absolute benefit derived is much lower than for comparable individuals without diabetes. In order to achieve improved outcomes in diabetes patients, it will be important to address other abnormalities in their lipid profiles, including elevated triglycerides and low HDL-C.     

Therapy to reduce risk of coronary heart disease

Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.     

Lipid peroxidation,antioxidants, lipid profile,and HbA1c in diabetic patients

Diabetes mellitus is characterized by hyperglycemia together with biochemical changes in glucose, lipid profile, lipid peroxidation, and antioxidants status. This study aims to assess lipid profile, lipid peroxidation, antioxidants, and glycated hemoglobin (HbA1c) in type 1 and type 2 diabetic subjects. Type 1 and type 2 diabetic patients were selected from the subjects attending OPD in Nepalgunj Medical College, Nepal, for medical checkup. Fasting blood sugar (FBS), lipid profile, lipid peroxidation (malondialdehyde), and antioxidants status (reduced glutathione and vitamin E) were estimated in both groups and were compared with healthy controls. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was calculated to assess the cardiovascular risk factors. When type 1 diabetic patients were compared with type 2 diabetic patients, it showed statistically significant increase in the levels of HbA1c, triglycerides (TGs), and high-density lipoprotein cholesterol (HDL-C), whereas statistically significant decreased level was found in malondialdehyde (MDA). FBS, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), vitamin E, and HDL/LDL ratio were not significant. Early diagnosis of dyslipidemia and oxidative stress can be used as a preventive measure for the development of microvascular and macrovascular complications in type 1 and type 2 diabetes mellitus.     

Effects of pioglitazone on lipid and lipoprotein metabolism

Type 2 diabetes is associated with an increased risk of cardiovascular disease (CVD). A major contributing factor to this risk is the abnormal lipid profile known as dyslipidaemia, which is characterized by low HDL cholesterol (HDL-C), raised triglycerides (TGs) and a predominance of small, dense LDL cholesterol (LDL-C) particles. Statins are now widely used first-line in patients with type 2 diabetes due to their proven efficacy in reducing LDL-C and cardiovascular risk. However, despite the use of statins, the absolute risk of CVD in patients remains elevated, highlighting the need to target all aspects of the diabetic lipid profile such as raised TGs or low HDL-C levels. Insulin resistance is thought to be central in the pathogenesis of diabetic dyslipidaemia; therefore, improving insulin sensitivity with a thiazolidinedione offers an attractive treatment option. Indeed, pioglitazone, a member of the peroxisome proliferator-activated receptor-gamma family, has been shown in clinical trials to improve both blood glucose levels and the lipid profile when used either as monotherapy or in combination with other oral antidiabetic agents. In the monotherapy setting, pioglitazone has been associated with greater decreases in TGs and increases in HDL-C when compared with glibenclamide or metformin. Studies investigating the effects of pioglitazone add-on therapy to either metformin or sulphonylurea treatments have shown sustained improvements in serum levels of TGs and HDL-C and favourable effects on LDL-C particle size. In comparison with rosiglitazone, pioglitazone has different and potentially favourable effects on plasma lipids. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events study has given weight to the hypothesis that the beneficial metabolic effects of pioglitazone may be associated with reductions in cardiovascular risk in patients with type 2 diabetes.     

血清尿酸水平与老年冠心病患者易感风险因素的相关性研究

目的分析血清尿酸水平与老年冠心病易感风险因素的相关性。方法回顾性采集2017年1月至2019年1月我医院老年冠心病患者200例(冠心病组)和同期医院门诊接诊的非冠心病老年患者150例(对照组)的临床资料。患者入院后即刻采集外周静脉血,测定血清尿酸水平;并记录各基线资料情况,将冠心病可能的易感风险因素纳入,经单因素与多因素分析找出风险因素,分析血清尿酸水平与老年冠心病患者各易感风险因素的相关性。结果初步单因素分析发现,吸烟、合并糖尿病、低高密度脂蛋白胆固醇(HDL-C)血症、冠心病家族史、肾小球滤过率等均可能是老年冠心病患者易感风险因素(χ^2=6.739、15.655、6.331、9.615、23.279,P均<0.05);多因素分析证实,吸烟、合并糖尿病、低HDL-C血症、冠心病家族史、肾小球滤过率均是老年冠心病易感风险因素(OR=1.777、2.381、1.883、1.967、3.205,均P<0.05);吸烟、合并糖尿病、低HDL-C血症、有冠心病家族史、肾小球滤过率<100 ml/min的老年冠心病患者,其血清尿酸水平均高于其他患者(t=8.017、5.907、8.509、7.164、13.839,均P<0.001);经Spearman相关性分析检验证实,血清尿酸水平与老年冠心病患者吸烟、合并糖尿病、冠心病家族史等易感风险因素均呈正相关(r=0.409、0.422、0.422,均P<0.001),与低HDL-C血症、肾小球滤过率呈负相关(r=-0.428、-0.481,均P<0.001)。结论血清高尿酸水平与吸烟、糖尿病等诸多冠心病易感风险因素有紧密联系,可能是冠心病发病的独立危险因素。     

Metabolisches Syndrom bei Patienten mit Diabetes mellitus Typ 1

BACKGROUND AND PURPOSE: Type 1 diabetes is known to be associated with increased cardiovascular disease in the presence of nephropathy and hypertension. It was the aim of the present study to elucidate whether or not clinical findings of metabolic syndrome (MS) are further increasing cardiovascular morbidity among type 1 diabetics. METHODS: In the present cross-sectional study, 1,241 type 1 diabetics were included. These patients attended the Diabetes Clinic Karlsburg, Germany, from February 1, 2002 to December 31, 2003. The presence of the following findings was taken into consideration as clinical features of MS in type 1 diabetes: fasting triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), daily insulin requirement/kg body weight (b.w.), increased blood pressure > 130/85 mmHg, including overt arterial hypertension. In each of the five categories the highest quintile in each sample was assessed: TG 2.9 +/- 3.6 mmol/l, HDL-C 1.48 +/- 0.46 mmol/l, BMI 29.1 +/- 4.98 kg/m(2) height, insulin requirement 0.71 +/- 0.23 IU/kg b.w., systolic blood pressure 130 +/- 12.3 mmHg. MS was defined as the presence of at least three categories. Among 1,241 type 1 diabetics (651 men, 590 women), 226 patients (129 men, 97 women) fulfilled the criteria of MS. The risk of MS was assessed by multiple regression analysis. Risk variables were: age, diabetes duration, sex, glycated hemoglobin (HbA(1c)), actual smoking, neuropathy, albumin excretion rate (AER), regular alcohol consumption, retinopathy, peripheral vascular disease (PVD), coronary heart disease (CHD), TGs, HDL-C, low-density lipoprotein cholesterol (LDL-C), cholesterol, blood pressure increase, BMI, increased insulin requirement, and foot syndrome. After adjusting for age, the variables were separately included into the mathematical model. The risk of MS was assessed after excluding the variables defining MS. RESULTS: Type 1 diabetics with MS were characterized by higher age (46 vs. 36 years; p < 0.01), and longer diabetes duration (19 vs. 16 years; p < 0.01). The risk of MS was independently associated (odds ratios) with higher age (40-59 years; 4.21; p < 0.01), increased HbA(1c) (1.41; p < 0.01), PVD (2.28; p < 0.01), CHD (2.19; p < 0.01), and the foot syndrome (4.17; p < 0.01). There were no significant associations of MS with type 2 diabetes heredity (first and second degree). CONCLUSION: Patients with type 1 diabetes and the presence of findings of MS are suffering from increased cardiovascular morbidity. The risk of MS increases with the age and HbA(1c). Life style factors such as weight gain and muscular inactivity seem to have an influence on the pathogenesis of MS in type 1 diabetes, thereby increasing cardiovascular morbidity.     

Low high-density lipoprotein cholesterol and cardiovascular disease: risk reduction with statin therapy

A low level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular disease; however, patients with low levels of HDL-C without raised low-density lipoprotein cholesterol (LDL-C) levels are not currently eligible for lipid-lowering therapy. Many individuals with low levels of HDL-C have a combination of cardiovascular risk factors that include high LDL particle concentrations. Lowering LDL particle concentration and its surrogate measure, LDL-C, is an important approach to reducing cardiovascular risk. Statins are the most effective agents for lowering levels of LDL and can significantly increase levels of HDL-C. Extending statin therapy to patients with low levels of HDL-C but with LDL-C levels below target may have benefits for cardiovascular disease reduction in these patients.     

The Role of Non-HDL Cholesterol in Risk Stratification for Coronary Artery Disease

Despite aggressive lipid-lowering therapy, patients continue to be at significant risk of coronary heart disease (CHD). Assessment of non–high-density lipoprotein cholesterol (non–HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the third Adult Treatment Panel (ATP III) guidelines of the US National Cholesterol Education Program, non–HDL-C was introduced as a secondary target of therapy in persons with triglycerides ≥200 mg/dL. A recent meta-analysis of the relationship between non–HDL-C reduction and CHD risk showed non–HDL-C as an important target of therapy for CHD prevention. Most lipid-modifying drugs used as monotherapy have a 1:1 relationship between percent non–HDL-C lowering and percent CHD reduction. In the EPIC-Norfolk prospective population study, 21,448 participants without diabetes or CHD between 45 and 79 years of age were followed for 11.0 years. Participants with high non–HDL-C levels were at increased CHD risk independently of their LDL-C levels. Also, compared to apolipoprotein B, non–HDL-C appears to be a better choice given the fact that no additional tests or costs are needed and established cut points are already available. Future guidelines should emphasize the importance of non–HDL-C for guiding cardiovascular prevention strategies with an increased need to have non–HDL-C reported on routine lipid panels.     

Managing the high-risk patient: therapeutic approaches in 2002

Populations of patients at high risk of coronary heart disease (CHD) include those with type 2 diabetes and those with heterozygous familial hypercholesterolemia (HeFH). Despite benefits of statin lipid-lowering therapy in reducing CHD risk in diabetic patients, screening for dyslipidemia in such patients is inadequate, and patients frequently fail to achieve recommended low-density lipoprotein goals. Diagnosis of HeFH is also suboptimal, despite the reliability of family lipid screening in confirming clinical diagnosis and utility of screening in identifying other family members who are at risk. Patients with HeFH frequently require large reductions in low-density lipoprotein (LDL) cholesterol to achieve target levels. In both of these populations, statins that produce large reductions in LDL cholesterol offer advantages in achieving lipid-lowering goals and in simplifying medical therapy to reduce CHD risk.