Increased plasma visfatin concentration is a marker of an atherogenic metabolic profile

Background and aimsVisfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables.Methods and resultsWhen study population (n = 179, age 49 ± 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles.ConclusionsOur results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk.     

Plasma HDL levels highly correlate with cognitive function in exceptional longevity

BACKGROUND: Families of centenarians have high levels of plasma high-density lipoprotein (HDL) cholesterol, which may have neurological as well as cardiovascular protective effects during aging. Because plasma HDL level declines progressively with aging, we examined whether centenarians with higher plasma HDL levels have better cognitive function. METHODS: Total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, HDL, triglycerides, and apolipoprotein levels were measured in a group of centenarians (N = 139; older than 95 years) and were correlated with their cognitive function (measured by Mini-Mental State Examination [MMSE]). RESULTS: Plasma HDL levels correlated significantly with MMSE (r =.32; p <.0001). Each decrease in plasma HDL tertile (74.9 +/- 2.1, 50.6 +/- 0.5, and 36.8 +/- 1.0 mg/dl) was associated with a significant decrease in MMSE (23.4 +/- 1.5, 17.7 +/- 1.8, and 12.4 +/- 1.8; p <.04 for each plasma HDL tertile). As expected, increased plasma apolipoprotein A-I and decreased plasma triglyceride levels were also correlated with a significantly superior cognitive function. Biological markers of hydration and nutritional status did not differ between the groups with the higher or lower plasma HDL or MMSE. CONCLUSIONS: These data demonstrate that cognitive dysfunction in centenarians is associated with a progressive decline in plasma HDL concentrations. This underscores the protective effects of increased plasma HDL and its role in maintaining superior cognition in longevity.     

Relation between on-treatment increments in serum high-density lipoprotein cholesterol levels and cardiac mortality in patients with coronary heart disease (from the Bezafibrate Infarction Prevention trial)

This study evaluated the association between changes in serum levels of high-density lipoprotein (HDL) cholesterol that occur under bezafibrate therapy and cardiac mortality in patients with coronary heart disease (CHD) who were enrolled in the Bezafibrate Infarction Prevention trial. We compared serum levels of HDL cholesterol in 1,509 patients in tertiles of on-treatment increments with those of 1,517 patients in the placebo group. Long-term follow-up showed that cardiac mortality decreased significantly with increasing tertiles of on-treatment change in HDL cholesterol (9.5%, 6.6%, and 6.3% of patients tertiles 1, 2, and 3, respectively, died of cardiac causes, p for trend = 0.02). In multivariate analysis, the magnitude of on-treatment increment of HDL cholesterol was independently associated with a decreased risk of cardiac death (hazard ratio 1.05, 95% confidence interval 0.74 to 1.47, for tertile 1; hazard ratio 0.73, 95% confidence interval 0.50 to 1.07, for tertile 2; hazard ratio 0.65, 95% confidence interval 0.43 to 0.97, for tertile 3, compared with placebo-allocated patients, p for trend = 0.02). Analyzing the association with change in HDL cholesterol as a continuous variable showed that the risk of cardiac mortality was decreased by 27% for every 5-mg/dl increase in on-treatment change in HDL cholesterol (p <0.001). In conclusion, although a definite secondary prevention effect of bezafibrate could not be found when examining the intervention group as a whole, our findings are consistent with a possible independent association between an increase in HDL cholesterol with bezafibrate therapy and a decrease in cardiac mortality. In appropriately selected patients, monitoring short-term response to bezafibrate therapy through change in HDL cholesterol may indicate the potential long-term benefit of the drug.     

Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.     

Effects of serum lipid levels on restenosis after coronary angioplasty.

Although the association of serum lipid levels with the risk of atherosclerosis is well-recognized, the relation between these levels and restenosis after coronary angioplasty is uncertain. This study examines 186 patients enrolled in a trial of fish oil for prevention of restenosis. Fasting lipid levels (cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides) were measured before angioplasty, and in 90 patients repeated at 6-month follow-up. Fifty-nine patients (32%) developed clinical restenosis confirmed by angiography. Patients who went on to develop restenosis underwent multivessel angioplasty (p less than 0.05) and were more likely to be on lipid-lowering therapy at baseline (27 vs 13%; p less than 0.05). In addition, they had higher baseline cholesterol/HDL ratios (6.5 +/- 2.2 vs 5.9 +/- 2.0; p less than 0.05) and triglyceride levels (233 +/- 210 vs 183 +/- 112 mg/dl; p less than 0.05). Multiple logistic regression analysis confirmed cholesterol/HDL ratios at baseline (p = 0.021) and follow-up (p = 0.0008) to be independent predictors of risk for restenosis. Using these data, regression lines have been developed that predict risk of restenosis based on type of procedure and on lipid values. These results suggest that serum lipid levels may be associated with the risk of clinical restenosis after coronary angioplasty.     

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.     

Relation between plaque progression and low-density lipoprotein cholesterol during aging as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound of the left main coronary artery

Because of the clinical benefit of lipid lowering in older patients, we hypothesized that the relation between low-density lipoprotein (LDL) cholesterol serum levels and coronary plaque progression may persist throughout aging. We analyzed serial intravascular ultrasound (IVUS) data of 60 left main stems (18 +/- 9 months apart) and evaluated the relation between LDL cholesterol levels and coronary plaque progression at different ages. The population (n = 60) was divided into 3 groups according to age: tertile 1 (n = 20) was a mean age of 48 +/- 6 years (median 51, range 33 to 55), tertile 2 (n = 20) was a mean age of 58 +/- 2 years (median 59, range 55 to 61), and tertile 3 (n = 20) was a mean age of 66 +/- 6 years (median 65, range 61 to 83). Between groups, there was no significant difference in non-age-related demographics, clinical data, lipid profiles, or medications (e.g., statins). There was a positive linear relation between LDL cholesterol and annual changes in plaque plus media area in all age tertiles, which was statistically significant in tertiles 2 and 3 (r = 0.56, p <0.01; r = 0.50, p <0.02) and showed a strong trend in tertile 1 (r = 0.41, p = 0.07). The estimated LDL cholesterol thresholds, which, as determined by regression analysis, would correspond to no plaque progression, were 74, 60, and 78 mg/dl, respectively, in tertiles 1, 2, and 3. In conclusion, serial IVUS data in left main coronary arteries suggest that the relation between LDL cholesterol serum levels and plaque progression persists during aging.     

Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease

OBJECTIVES: The joint predictive value of lipid and C-reactive protein (CRP) levels, as well as a possible interaction between statin therapy and CRP, were evaluated for survival after angiographic diagnosis of coronary artery disease (CAD). BACKGROUND: Hyperlipidemia increases risk of CAD and myocardial infarction. For first myocardial infarction, the combination of lipid and CRP levels may be prognostically more powerful. Although lipid levels are often measured at angiography to guide therapy, their prognostic value is unclear. METHODS: Blood samples were collected from a prospective cohort of 985 patients diagnosed angiographically with severe CAD (stenosis > or =70%) and tested for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and CRP levels. Key risk factors, including initiation of statin therapy, were recorded, and subjects were followed for an average of 3.0 years (range: 1.8 to 4.3 years) to assess survival. RESULTS: Mortality was confirmed for 109 subjects (11%). In multiple variable Cox regression, levels of TC, LDL, HDL and the TC:HDL ratio did not predict survival, but statin therapy was protective (adjusted hazard ratio [HR] = 0.49, p = 0.04). C-reactive protein levels, age, left ventricular ejection fraction and diabetes were also independently predictive. Statins primarily benefited subjects with elevated CRP by eliminating the increased mortality across increasing CRP tertiles (statins: HR = 0.97 per tertile, p-trend = 0.94; no statins: HR = 1.8 per tertile, p-trend < 0.0001). CONCLUSIONS: Lipid levels drawn at angiography were not predictive of survival in this population, but initiation of statin therapy was associated with improved survival regardless of the lipid levels. The benefit of statin therapy occurred primarily in patients with elevated CRP.     

High-density lipoprotein cholesterol is reduced in patients with sarcoidosis

PURPOSE: Sarcoidosis is a disease in which the proliferation of monocyte-macrophage-derived cells is observed. In other diseases characterized by expansion of the monocyte-macrophage system, such as Gaucher's disease and myeloid metaplasia, abnormalities of lipoprotein metabolism have been demonstrated. To determine whether similar abnormalities in lipoprotein cholesterol concentrations could be identified in patients with sarcoidosis, we studied total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol as well as triglyceride levels in 52 patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: Patients had no other medical disorders and were not being treated with corticosteroids or antimalarial agents. Blood samples were collected by venipuncture after an overnight fast. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoprotein cholesterol was quantified by lipoprotein fractionation. HDL cholesterol was measured as cholesterol remaining in the supernatant after precipitation of LDL and very-low-density lipoprotein from whole plasma by the heparin-maganese chloride method. Computation was used to determine the level of LDL cholesterol. RESULTS: We found significantly reduced levels of total cholesterol (183.9 +/- 27.6 versus 194.3 +/- 16.5 mg/dl, mean +/- SD, p = 0.021) and HDL cholesterol (41.2 +/- 13.0 versus 51.9 +/- 6.1 mg/dl, p = 0.0001) in sarcoid patients versus an age-, sex-, and race-matched reference group. Differences were not observed in triglyceride or LDL cholesterol levels (p greater than 0.05). CONCLUSION: These findings are similar to those observed in the myeloproliferative diseases, Gaucher's disease, and rheumatoid arthritis and suggest a functional role for monocytes-macrophages in the regulation of serum lipoprotein cholesterol levels.     

A cross-sectional study of lipids and ApoC levels in Alzheimer's patients with and without cardiovascular disease

BACKGROUND: There is increasing evidence supporting the role of atherogenic phenomena in Alzheimer's disease (AD). The possible significance of specific plasma lipid levels in the pathogenesis of AD remains controversial. While lipids such as cholesterol or chaperons such as apolipoprotein (Apo) E2 to ApoE4 have been assessed in AD, ApoC2 and ApoC3 have not been studied before. The present study investigated possible differences in levels of these lipids in AD patients, with or without cardiovascular diseases or risk factors. METHODS: This is a cross-sectional study. The medical charts of patients diagnosed with probable AD were screened for the presence of cardiovascular disease and cardiovascular risk factors. Included in the study were 105 AD patients: 53 with cardiovascular risk factors (AD(+CVD)) and 52 without risk factors (AD(-CVD)). Blood samples were analyzed for lipoproteins, ApoC2, and ApoC3. We used t tests, chi-square tests, and regression analyses to identify significant differences and to compare the relationships of variables among the groups. RESULTS: ApoC2 levels (3.5 +/- 0.3 and 3.4 +/- 0.4 mg/dl, respectively), ApoC3 (13.7 +/- 0.9 and 14.7 +/- 1.1 mg/dl, respectively), and high-density lipoprotein (HDL)/non-HDL ApoC3 ratios (1.6 +/- 0.2 and 1.3 +/- 0.2, respectively) were similar for the AD patients with and without cardiovascular risk factors. Levels of total cholesterol, triglycerides, low-density lipoproteins (LDL), very LDLs, and HDLs were similar in the two groups. A substantial proportion of both AD(+CVD) and AD(-CVD) patients showed high levels of total cholesterol and LDL, as well as low levels of HDL, ApoC2, and ApoC3, compared to normative values. Surprisingly, patients treated by cognitive enhancers showed significantly higher cholesterol ( p =.002) and triglyceride ( p =.015) levels, independent of age, gender, and cognitive level. CONCLUSIONS: There was no difference between AD patients, either with or without cardiovascular diseases or risk factors, with respect to plasma lipid profile, including ApoC2 and ApoC3. This could indicate that lipid metabolism may play a role in AD, whether with or without cardiovascular risk factors. The higher levels of some lipids, observed in a subset of patients treated by cognitive enhancers, deserves further investigation.     

A genome-wide scan of serum lipid levels in the Old Order Amish

Elevated serum low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) and decreased high density lipoprotein cholesterol (HDL-C) levels are established risk factors for cardiovascular disease (CVD). To identify quantitative trait loci influencing lipid levels, we conducted genome-wide linkage analyses of total serum cholesterol (TSC), HDL-C, ln-transformed TG (LNTG) and LDL-C levels in 612 individuals from 28 families of the Amish Family Diabetes Study (AFDS). Subjects were genotyped for 373 microsatellite markers covering all 22 autosomes and the X chromosome at an average density of 9.7 centimorgans. All lipid traits exhibited moderate estimated heritability (h2 +/- S.E.): TSC, 0.63 +/- 0.11; HDL-C, 0.54 +/- 0.08; LNTG, 0.37 +/- 0.08; LDL-C, 0.62 +/- 0.10. The highest logarithm of the odds (LOD) score observed was 2.47 (P = 0.0003), at 3p25 for LDL-C. LOD scores exceeding 2.0 (P < 0.001) were also observed at 2p23 (LOD = 2.17) and 19p13 (LOD = 2.23) for LDL-C, and at 11q23 (LOD = 2.03) for LNTG. Three additional regions exhibited LOD scores greater than 1.5, corresponding to a P-value of <0.005. Many of the regions suggestively linked in this genome-wide scan contain genes encoding proteins with established roles in lipid metabolism, including apolipoproteins, peroxisome proliferater-activated receptor-gamma and the LDL receptor.     

LDL size in African Americans, Hispanics, and non-Hispanic whites : the insulin resistance atherosclerosis study.

The prevalence of cardiovascular disease (CVD) and atherosclerosis varies among several minority ethnic groups in the United States. Recently, small, dense low density lipoprotein (LDL) particle size has been recognized as a risk factor for CVD. We examined LDL size as a possible explanation for differences in CVD rates in 1571 subjects from the Insulin Resistance Atherosclerosis Study (IRAS), a multiethnic study of insulin resistance and cardiovascular risk factors. LDL size (A) was significantly different by ethnic group (African Americans 262.1+/-0.6, Hispanics 257.6+/-0.6, and non-Hispanic whites 259.2+/-0.4, P<0.001). Ethnic differences in LDL size continued to be statistically significant after adjustment for upper body adiposity, insulin resistance, and glucose tolerance status. However, after further adjustment for other cardiovascular risk factors, especially ethnic differences in triglyceride and high density lipoprotein (HDL) cholesterol levels, the ethnic differences in LDL size were markedly attenuated and in general no longer statistically significant. The relation of triglyceride, HDL cholesterol, insulin resistance, and adiposity to LDL size in each ethnic group was similar. LDL size differs by ethnic group, which is independent of obesity or insulin resistance. These ethnic differences appear to be due to ethnic variations in dyslipidemia (especially differences in triglyceride levels); ethnic differences in LDL size are not consistent with previously reported ethnic dissimilarities in CVD or atherosclerosis.     

Association of white blood cell count with systolic blood pressure within the normotensive range

Hypertension and inflammation promote cardiovascular disease (CVD). Even high normal systolic blood pressure (SBP) is associated with increased CVD risk. We assessed the relationship of elevated SBP within the normotensive range and white blood cell (WBC) count. This is a cross-sectional study of 3484 white asymptomatic individuals (mean age: 43+/-8 years, 79% males) without hypertension with SBP<140 mm Hg. White blood cell count >or=75th percentile (8.35 x 10(9) cells/l) was considered cutoff for elevated WBC. Subjects were classified into three levels of SBP (first: <120 mm Hg, n=1,176, 34%; second: 120-129 mm Hg, n=1,654, 47%; third: 130-139 mm Hg, n=654, 19%). Mean WBC count increased linearly across SBP categories (first: 6.14+/-1.54, second: 6.20+/-1.52, third: 6.41+/-1.62, P=0.02 for trend). There was a linear increase in prevalence of elevated WBC across higher SBP categories (22, 24 and 28%, P=0.02). As compared to those with SBP<120 mm Hg, in multivariate linear regression analyses (adjusting for age, gender, smoking status, diabetes, body mass index, physical activity, cholesterol/high-density lipoprotein cholesterol ratio) WBC count was significantly higher among participants with SBP 130-139 mm Hg (regression coefficient: 2.64, 95% confidence interval: 1.04-4.24, P=0.001). Odds ratio for prevalence of elevated WBC with SBP<120 mm Hg as reference group was 1.14 (0.92-1.41) for SBP 120-129 mm Hg and 1.50 (1.15-1.92) for SBP 130-139 mm Hg. In conclusion, Higher SBP within the normotensive range is also associated with elevated WBC count. Further studies are needed to clarify the role of inflammation in high normal SBP and associated CVD risk.     

Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels

A sample of 2,103 men aged 47 to 76 years from the Québec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (.62 < or = r < or = .75, P < .0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (.78 < or = r < or = .85 and .83 < or = r < or = .86 for LDL-C and non-HDL-C, respectively, P < .0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r = .37; P < .0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).     

Effect of acute myocardial infarction on cholesterol ratios

OBJECTIVE: In patients with acute myocardial infarctions (MIs), cholesterol levels are no longer valid after 24 h from presentation because acute MI causes a rapid decline in serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. The objective of this study was to evaluate the effect of acute MI on the total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio. METHODS: The study consisted of 45 patients who were admitted to the hospital with acute MIs. Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were determined on day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio were calculated. Serum lipid levels and cholesterol ratios were compared between day 1 post-MI and day 4 post-MI. RESULTS: From day 1 post-MI to day 4 post-MI, the mean (+/- SD) serum levels of total cholesterol (188.4 +/- 52.5 vs. 170.5 +/- 57.2 mg/dL, respectively; p = 0.01), LDL cholesterol (120.3 +/- 48.9 vs. 105.9 +/- 43.0 mg/dL, respectively; p = 0.009), and HDL cholesterol (45.0 +/- 18.5 vs 39.3 +/- 16.1 mg/dL, respectively; p < 0.001) decreased, but the mean serum level of triglycerides (119.2 +/- 81.2 vs 149.3 +/- 68.3 mg/dL, respectively; p = 0.006) increased. The cholesterol ratios, however, remained unchanged between day 1 post-MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio was 4.59 +/- 1.84 on day 1 post-MI and 4.67 +/- 1.77 on day 4 post-MI (change not significant). The LDL cholesterol/HDL cholesterol ratio was 2.96 +/- 1.58 on day 1 post-MI and 2.99 +/- 1.44 on day 4 post-MI (change not significant). CONCLUSION: Acute MI does not affect the cholesterol ratios. Therefore, when the absolute levels of serum cholesterol are no longer valid (beyond 24 h after an MI), the cholesterol ratios still could be useful for cholesterol risk assessment in patients with acute MIs.     

Plasma lipid lowering effects of doxazosin, a new selective alpha1 adrenergic inhibitor for systemic hypertension

Hypertension and hypercholesterolemia are 2 major risk factors for atherosclerotic coronary artery disease (CAD). Elevations of both blood pressure and serum cholesterol levels should be reduced to control CAD risk. Doxazosin is a once-daily, long-acting, selective alpha 1-adrenergic inhibitor that is effective for the treatment of essential hypertension. During controlled studies of doxazosin's antihypertensive efficacy, 3 serum lipid parameters were measured; total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol. In 10- to 12-week placebo-controlled studies, 142 doxazosin-treated patients were compared with 155 placebo-controlled subjects. Doxazosin patients had an increase of 8.9% in the HDL/total cholesterol ratio (p less than 0.05), whereas total cholesterol, HDL cholesterol and triglyceride levels were not significantly different between the 2 study groups. During a 52-week comparison of doxazosin versus atenolol, doxazosin treatment was associated with a significant decrease in total triglyceride levels (5%; p less than 0.001) and increases in HDL cholesterol levels (3.9%; p less than 0.01) and HDL/total cholesterol ratio (5.4%; p less than 0.0001). Doxazosin is an effective antihypertensive agent that has a favorable impact on serum lipid levels, thereby promoting a beneficial effect on 2 major CAD risk factors.     

Variation in cholesterol, lipoproteins and triglycerides after heart transplantation in children]

Total cholesterol, HDL and LDL-cholesterol and triglyceride levels may contribute to the development or progression of coronary artery disease of the transplanted heart. The aim of this retrospective study was to determine the short and long-term lipid profiles of transplanted children and to identify factors influencing these dyslipidemias. Twenty-three patients aged 9.5 +/- 5.9 years at cardiac transplantation were followed up for 5.8 +/- 3.1 years. All were on triple therapy with normal diets. The total cholesterol increased by 17% during the first year (4.47 +/- 1.01 mMol/l to 5.25 +/- 1.22 mMol/l at 1 year: p < 0.05) with a peak at 3 months of 5.31 +/- 1.28 mMol/l correlating with the dosage of prescribed corticosteroids. LDL-cholesterol levels increased by 20% during the first year (2.26 +/- 0.67 mMol/l to 3.29 +/- 0.99 mMol/l at 1 year: p = 0.018). HDL-cholesterol levels increased from 1.02 +/- 0.27 mMol/l to a maximum of 1.55 +/- 0.4 mMol/l at 1 year, p < 0.05. Lipoprotein A1, a protecting sub-fraction of HDL, did not change significantly. Changes in triglyceride levels were not significant despite a tendency to hypertriglyceridaemia in the early phases. After one year, serum cholesterol and lipoprotein levels remained higher than the initial values. These results show that cardiac transplant children are exposed to the risk of atherogenic hyperlipidaemia and require systematic lipid profile monitoring, dietary advice and lipid lowering drugs.     

Rhesus positivity and low high-density lipoprotein cholesterol: a new link?

The aim of the study was to investigate the relationship of ABO and Rh blood groups with lipid profile in patients with established multivessel coronary artery disease in a population with low levels of high-density lipoprotein cholesterol. The records of 978 patients with multivessel coronary artery disease, in whom coronary bypass surgery was performed, were investigated. Coronary risk factors including diabetes, hypertension, smoking, and obesity were noted for each patient. Serum lipid profiles: total cholesterol, low-density and high-density lipoprotein cholesterol, and triglyceride levels, were also recorded. The mean age of the patients was 59.3 +/- 9.7 years (range, 25-84 years) and 80% were male. The risk factors and lipid profiles of ABO blood types were similar. Rh-negative patients had higher levels of high-density lipoprotein cholesterol (46.9 +/- 9.9 vs. 41.6 +/- 10.4 mg.dL(-1), p = 0.001) and a lower total/high-density lipoprotein cholesterol ratio (4.8 +/- 1.3 vs. 5.2 +/- 1.6, p = 0.029) compared to Rh-positive patients. The other lipid levels and risk factors had no association with Rh typing. These results indicate a significant association between rhesus positivity and low levels of high-density lipoprotein cholesterol in patients with multivessel coronary artery disease.     

Comparison of high-density and low-density lipoprotein cholesterol subclasses and sizes in Asian Indian women with Caucasian women from the Framingham Offspring Study

BACKGROUND: Asian Indian women have a higher rate of coronary artery disease (CAD) than do other ethnic groups, despite similar conventional risk factors and lipid profiles. Smaller high-density lipoprotein cholesterol (HDL-C) particle size is associated with reduced cardiac protection or even an increased risk of CAD. Exceptional longevity correlates better with larger HDL-C particle sizes. HYPOTHESIS: Higher rates of CAD among Asian Indian women may partly be explained by the differenes in the prevalence of atherogenic HDL-C and low-density lipoprotein cholesterol (LDL-C) sizes and their subclass concentrations among Asian Indian women compared with Caucasian women. METHODS: We measured HDL-C concentrations and sizes by nuclear magnetic resonance spectroscopy in 119 relatively healthy Asian Indian women and compared them with those of 1752 Caucasian women from the Framingham Offspring Study (FOS). RESULTS: Asian Indian women were significantly younger (47.9 +/- 11.2 vs. 51.0 +/- 10.1 years, p = 0.0001), leaner (body mass index 24.0 +/- 4.7 vs. 26.0 +/- 5.6, p = < 0.0002), less likely to be postmenopausal (32 vs. 54%, p = < 0.0001), or smoke (< 1 vs. 20%, p = < 0.0001); nevertheless, prevalence of CAD was higher in Asian Indian women (4.2 vs. 1%, p = 0.0006). Asian Indian women had similar HDL-C (53 +/- 13 vs. 53 +/- 13 mg/dl, p = 0.99), smaller HDL-C particle size (8.9 +/- 0.35 vs. 9.4 +/- 0.44 nm, p = < 0.0001), higher total cholesterol (209 +/- 40 vs. 199 +/- 42 mg/dl, p = 0.01), and similar triglyceride (120 +/- 77 vs. 108 +/- 110 mg/d, p = 0.24) levels. Low-density lipoprotein cholesterol, particle concentrations and sizes, as well as prevalence of pattern B were similar. CONCLUSIONS: Compared with the FOS, Asian Indian women have significantly smaller overall HDL particle size and similar levels of HDL-C, which may reflect impaired, reverse cholesterol transport. Total cholesterol was higher, whereas triglyceride and LDL-C levels were similar. This may partly explain the higher CAD rates in Asian Indian women. Further large scale, prospective, long-term studies are warranted.