Low serum high-density lipoprotein cholesterol in obese subjects with normal serum triglycerides: the role of insulin resistance and inflammatory cytokines

BACKGROUND: The cause of obesity-related low HDLc in the absence of hypertriglyceridemia is not known. SUBJECTS & METHODS: A total of 32 subjects with a body mass index (BMI)(kg/m(2)) greater than 30 and normal serum triglycerides (<150 mg/dl) were identified. RESULTS: People with low HDLc (n = 16) compared to those with normal HDLc (n = 16) had higher BMI (37.53 +/- 4.54 vs. 33.99 +/- 3.65 kg/m(2), p < 0.021), higher body fat weight (42.59 +/- 9.51 vs. 34.76 +/- 8.7 kg, p < 0.023), and higher insulin resistance index (3.75 +/- 2.51 vs. 1.95 +/- 1.10, p < 0.013). Seven subjects with low HDLc and none of those with normal HDLc, had elevated serum tumor necrosis factor alpha and/or interleukin-6 (p < 0.010). CONCLUSIONS: Low HDLc levels can occur in obesity independently of elevated serum triglycerides and may be secondary to elevated serum levels of inflammatory cytokines.     

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.     

Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.     

Independent role of blood pressure on cardiovascular risk factors in nondiabetic,obese African-American women with family history of type 2 diabetes: Implications for metabolic syndrome components

African-American women (AAW) suffer disproportionately from hypertension and its consequences. We investigated the significance of systolic and diastolic blood pressure (SBP/DBP) as components of metabolic syndrome (MetS) in nondiabetic, overweight/obese AAW. We studied 258 AAW (mean age, 42.4 ± 8.4 years and body mass index (BMI), 33.4 ± 8.0 kg/m²) in a cross-sectional manner. We estimated the prevalence of MetS and its components using Adult Treatment Panel (ATP III) criteria, insulin sensitivity (Si), insulin resistance (HOMA-IR), and cardiovascular disease risk factors according to the tertiles of blood pressure (BP). Mean age and BMI did not differ with increases in BP tertiles. At screening, 35.7% of our subjects were hypertensive. MetS was found in 32.2% of our AAW. Prevalence of MetS increased as the tertiles of BP increased (SBP = first [10.5%], second [15.1%], third [58.1%], and DBP = first [9.3%], second [23.3%], third [54.7%]). We found that the components of Adult Treatment Panel (ATP) did not track with the corresponding BP tertiles. However, the prevalence of individuals meeting ATP III criteria for BP was highest in the third tertile of both SBP and DBP. Consequently, the prevalence of MetS was highest in the third vs. first and second tertiles. Using linear regression analysis, SBP and DBP did not correlate with the conventional cardiovascular risk factors, HOMA-IR, or Si. In overweight/obese AAW, we found the components of MetS do not track with BP. In the absence of elevated BP, the prevalence of MetS appears to be very low in overweight and obese AAW. Conversely, elevated BP or hypertension was associated with remarkably higher rates of MetS in our AAW. Therefore BP criteria constitute an important and independent determinant of ATP III definition of MetS in AAW.     

High triglycerides/low high-density lipoprotein cholesterol,ischemic electrocardiogram changes,and risk of ischemic heart disease

Background High triglycerides (TG)/low high-density lipoprotein cholesterol (HDL-C)(TG ≥1.60 and HDL-C ≤1.18 mmol/L) and ischemic ST-T changes in the resting electrocardiogram (ECG) are both strong risk factors of ischemic heart disease (IHD) in men without clinical cardiovascular diseases. This study tested the hypothesis that men free of clinical IHD with high TG/low HDL-C and resting ischemic ECG changes would have a particularly poor prognosis with respect to IHD.Methods We conducted a cohort study of 2906 men, aged 53 to 74 years, without overt IHD at baseline.Results During 8 years, IHD developed in 229 men; 61 cases were fatal. Of the risk factors recorded, ischemic ECG changes and high TG/low HDL-C were the strongest risk factors of IHD. Compared with men without high TG/low HDL-C and without ischemic ECG changes, age-adjusted relative risk of total IHD (95% CI) was 3.5 (1.7-7.2) in men with both high TG/low HDL-C and ischemic ECG changes; the corresponding value for fatal IHD was 11.2 (4.9-25.8). Adjusted for conventional risk factors, the interaction term high TG/low HDL-C × ischemic ECG changes was a significant predictor of IHD death, with a relative risk of 2.6 (1.0-6.9).Conclusions In men free of clinical IHD, ischemic ECG changes were significantly more predictive of fatal IHD in men with high TG/low HDL-C, indicating an adverse synergistic effect of these 2 risk factors. (Am Heart J 2003;145:103-8.)     

Metabolic syndrome, low-density lipoprotein cholesterol, and risk of cardiovascular disease: a population-based study

We sought to examine the relative contribution to cardiovascular risk of the metabolic syndrome (MS) compared with that of a high LDL cholesterol level in a population-based study of 2493 men and women, age 41-72 years, without major cardiovascular diseases at baseline. MS was defined according to the National Cholesterol Education Program criteria. The study population was subdivided into four groups on the basis of presence (prevalence: 15%) or absence of MS (85%) and presence (15%) or absence of high LDL cholesterol (85%) defined as a level >5.02 mmol/L or 5.02 mmol/L (12%), 1.80 (1.26-2.57) in subjects with MS and LDL cholesterol 5.02 mmol/L (3%). In a general population, MS was associated with a cardiovascular risk comparable with that of a high LDL cholesterol level.     

Accuracy of the ratio of triglycerides to high-density lipoprotein cholesterol for predicting low-density lipoprotein cholesterol particle sizes, phenotype B, and particle concentrations among Asian Indians

Asian Indians have unusually high rates of coronary artery disease. Small low-density lipoprotein (LDL) particle predominance (phenotype B) is associated with a fourfold atherogenic risk. This study examined the accuracy of a triglyceride/high-density lipoprotein cholesterol (HDL) ratio of > or =3.8 (determined from the Adult Treatment Panel III guidelines, normal triglycerides <150 mg/dl and HDL >40 mg/dl) for predicting phenotype B in Asian Indians. Fasting blood samples were collected from 150 healthy Asian Indians. LDL size analysis was performed by nuclear magnetic resonance spectroscopy. The triglyceride/HDL cholesterol ratio correlated inversely with the LDL size and positively with the particle concentration. A triglyceride/HDL cholesterol ratio of > or =3.8 had 76% sensitivity, 93% specificity, and 83% positive and 89% negative predictive values for predicting phenotype B.     

Smoking prevents the intravascular remodeling of high-density lipoprotein particles: implications for reverse cholesterol transport

Smoking is a leading cause of atherosclerosis acting trough a wide spectrum of mechanisms, notably the increase of the proatherogenic effect of dyslipidemia. However, a severe atherosclerotic disease is frequently observed in smokers who do not present an overt dyslipidemia. In the present study, we sought to determine if abnormalities in lipid metabolism occur in normolipidemic smokers, focusing especially on the components of intravascular remodeling of high-density lipoprotein (HDL) For this purpose, we measured lipid transfer proteins and enzymes involved in the reverse cholesterol transport (RCT) system in 29 adults: 15 smokers and 14 controls. The blood samples were drawn in the fasting state, immediately after the smokers smoked 1 cigarette. The composition of HDL particles was analyzed after isolation of HDL fractions by microultracentrifugation. We observed that normolipidemic smokers present higher total plasma and HDL phospholipids (PL) (P < .05), 30% lower postheparin hepatic lipase (HL) activity (P < .01), and 40% lower phospholipid transfer protein (PLTP) activity (P < .01), as compared with nonsmokers. The plasma cholesteryl ester transfer protein (CETP) mass was 17% higher in smokers as compared with controls (P < .05), but the endogenous CETP activity corrected for plasma triglycerides (TG) was in fact 57% lower in smokers than in controls (P < .01). Lipid transfer inhibitor protein activity was also similar in both groups. In conclusion, the habit of smoking induces a severe impairment of many steps of the RCT system even in the absence of overt dyslipidemia. Such an adverse effect might favor the atherogenicity of smoking.     

高密度脂蛋白胆固醇与心脑血管病相关性前瞻研究

目的 探讨我国35～64岁人群血清HDL-C水平与急性冠心病事件和急性卒中事件发病危险的关系.方法 采用前瞻性队列研究的方法 ,对11省市35～64岁队列人群共30 384人基线HDL-C水平和1992-2003年发生的急性冠心病和急性卒中事件关系进行分析.应用Cox比例风险模型对HDL-C水平与心血管病发病危险进行多因素分析.结果 (1)与对照组相比,随着HDL-C水平的降低,缺血性心血管病(ICVD)事件发病危险呈持续增加.(2)HDL-C水平与不同类型的心血管病发病危险的关系有所差别,随着HDL-C水平的降低,急性冠心病事件发病危险及缺血性卒中事件发病危险明显上升;而出血性卒中事件与HDL-C水平的关系差异无统计学意义.低HDL-C血症组急性冠心病发病的危险增加45%(RR=1.45,P＜0.05),缺血性卒中发病的危险增加53%(RR=1.53,P＜0.01).(3)在缺血性心血管病事件中,6.4%可归因于HDL-C水平降低;其中6.2%的急性冠心病事件和7.3%的急性缺血性卒中事件可归因于低HDL-C血症.结论 从HDL-C≥1.56mmol/L开始,随着HDL-C水平的降低,ICVD的发病危险明显上升.在血脂异常的防治中,对于低HDL-C应予以足够重视.     

A prospective cohort study on risk of acute pancreatitis related to serum triglycerides,cholesterol and fasting glucose

Background/objectivesTo investigate risk for acute pancreatitis related to moderately elevated triglycerides, cholesterol and fasting glucose.MethodsThis was a prospective cohort study in Malmö, Sweden of 33 346 subjects investigated 1974–1992 and followed until December 31, 2006. Baseline investigation included a self-administered questionnaire and analysis of serum triglycerides, cholesterol and fasting glucose. Cases of acute pancreatitis (n = 277, median time since baseline investigation 15.6 years) were identified in diagnosis registries and validated retrospectively. Attacks were classified as obstructive or non obstructive (alcohol or non alcohol related). Cox proportional hazards analysis was used to calculate hazard ratios (HR) for acute pancreatitis related to relevant risk factors, adjusting for age, sex, smoking habits and alcohol consumption.ResultsTriglycerides were associated with overall, non obstructive and non obstructive non alcohol related acute pancreatitis with adjusted HRs of 1.21 (95% confidence interval (CI), 1.07–1.36), 1.23 (95% CI, 1.06–2.43) and 1.34 (95% CI, 1.11–1.62) per 1 mmol/l increment, respectively. Corresponding HRs for forth versus first quartile of triglycerides were 1.55 (95% CI, 1.09–2.21), 1.60 (95% CI, 1.60–1.01–1.35) and 2.07 (95% CI, 1.13–3.79). Triglycerides were not associated with obstructive acute pancreatitis and there were no associations between glucose or cholesterol and the risk of acute pancreatitis.ConclusionsWe found an association between prediagnostic levels of triglycerides and risk for acute pancreatitis. This association was most pronounced in the non obstructive non alcohol related group. Our findings suggest that triglycerides may be a more important risk factor for acute pancreatitis than what has previously been estimated.     

Association of the triglycerides to high-density lipoprotein cholesterol ratio with the risk of chronic kidney disease: Analysis in a large Japanese population

Objectives

To investigate the relationship between triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) and chronic kidney disease (CKD).

Methods

We used data from 216,007 Japanese adults who participated in a nationwide health checkup program. Men (n = 88,516) and women (n = 127,491) were grouped into quartiles based on their TG/HDL-C levels (<1.26, 1.26–1.98, 1.99–3.18, and >3.18 in men; <0.96, 0.96–1.44, 1.45–2.22, and >2.22 in women). We cross-sectionally assessed the association of TG/HDL-C levels with CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² (low eGFR) and/or proteinuria (defined as urinary protein ≥1+ on dipstick testing)], low eGFR, and proteinuria.

Results

The prevalence of CKD, low eGFR, and proteinuria increased significantly with elevating quartiles of TG/HDL-C in both genders (all P for trend <0.001). Participants in the highest quartile of TG/HDL-C had a significantly greater risk of CKD than those in the lowest quartile after adjustment for the relevant confounding factors (odds ratio: 1.57, 95% confidence interval: 1.49–1.65 in men; 1.41, 1.34–1.48 in women, respectively). Furthermore, there were significant associations with low eGFR and proteinuria. In stratified analysis, the risk of CKD increased linearly with greater TG/HDL-C levels in participants with and without hypertension, diabetes, and obesity. Moreover, higher TG/HDL-C levels were relevant for CKD, especially in participants with hypertension and diabetes (P for interaction <0.001, respectively).

Conclusions

An elevated TG/HDL-C is associated with the risk of CKD in the Japanese population.     

Apolipoprotein E predicts incident cardiovascular disease risk in women but not in men with concurrently high levels of high-density lipoprotein cholesterol and C-reactive protein

Although there is great interest in the notion that dysfunctional transformation of high-density lipoprotein (HDL) facilitates development of atherosclerosis and cardiovascular disease (CVD), few studies in human populations directly address this issue. As apolipoprotein E (apoE) is a constituent of HDL thought to be important for HDL antiatherogenic function, we sought to assess the role of apoE in CVD risk in subjects likely to display dysfunctional transformation of HDL. Association of apoE levels with incident CVD risk was investigated using Cox multivariable proportional hazards modeling. Analyses were performed in subgroups of women and men likely to display dysfunctional transformation of HDL deriving from previous subgroup identification based upon defining characteristics of concurrently high levels of HDL cholesterol and systemic inflammation as reflected by high C-reactive protein levels. Results revealed apoE levels (dichotomized as highest quartile vs combined 3 lowest quartiles) as predicting subgroup risk in women (hazard ratio, 4.52; 95% confidence interval, 1.07-19.12; P = .040) but not in men. Further sex differences were manifested in terms of the relationship of apoE levels with age. Analysis revealed positive correlation of apoE levels with age in women (r = 0.47, P < .0001) but not in men (r = 0.04, P = .43). Apolipoprotein E levels predict incident CVD risk in women with high levels of HDL cholesterol and C-reactive protein but not in men. Future studies should be oriented toward investigations of apoE as related to multiplicity of HDL functionality and toward assessment of potential roles for apoE in dysfunctional transformation of HDL.