Impact of paraoxonase polymorphism (Q192R) on endothelial function in intact coronary circulation.

Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.     

Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans

OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 microg/min) and BK (62.5 ng/min and 4 microg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype.     

Relationship between plasma oxidized low-density lipoprotein and the coronary vasomotor response to acetylcholine in patients with coronary artery disease

The present study examined the relation of plasma oxidized low-density lipoprotein (LDL) levels to plasma LDL cholesterol levels and the impairment of endothelium-dependent coronary vasorelaxation in patients with coronary artery disease (CAD). In the first study, the relationship between plasma levels of oxidized LDL and LDL cholesterol were investigated in 88 patients with CAD. In the second study, the changes in the diameter of the left anterior descending (LAD) and the left circumflex (LCX) coronary arteries were measured after intracoronary administration of acetylcholine (15 microg) and isosorbide dinitrate (2.5 mg) in 15 patients with CAD. Plasma oxidized LDL levels were determined with a sandwich enzyme-linked immunosorbent assay. Plasma oxidized LDL levels did not correlate with plasma LDL cholesterol levels (r=-0.03, p=NS). The % diameter changes (mean+/-SEM) in the LAD and LCX after intracoronary acetylcholine were -8.3+/-3.5% and -10+/-4.2%, respectively. The % diameter changes in the LAD and LCX after intracoronary isosorbide dinitrate were 23+/-4.8% and 23+/-5.1%, respectively. The % diameter changes in the LAD and LCX inversely correlated with plasma oxidized LDL levels after intracoronary acetylcholine (LAD: r=-0.55, p=0.03; LCX: r=-0.59, p=0.02), but were not after intracoronary isosorbide dinitrate. Plasma LDL cholesterol, triglyceride, and high-density lipoprotein cholesterol levels did not correlate with the coronary vasoreaction to acetylcholine. In conclusion, plasma oxidized LDL levels do not correlate with plasma LDL-cholesterol levels and are related to impairment of endothelium-dependent coronary vasodilation in patients with CAD.     

Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms

STUDY OBJECTIVES: Improvement in coronary artery endothelial function has been demonstrated after cholesterol lowering in hypercholesterolemic patients with significant atherosclerosis. However, to our knowledge, no previous study has shown improvement in resistance artery function in subjects with normal coronary arteries after cholesterol lowering. The purpose of our study was to investigate the effect of cholesterol lowering with pravastatin on coronary resistance artery endothelial function in the setting of angiographically normal coronary arteries. METHODS: Invasive testing of coronary endothelial and vasomotor function was performed at baseline and after 6 months of pravastatin treatment in six patients with normal coronary arteriograms. RESULTS: After 6 months of pravastatin treatment, low-density lipoprotein cholesterol level dropped from 157+/-11 to 117+/-8 mg/dL (p = 0.02) and percent increase in coronary blood flow after acetylcholine improved from 97+/-13% to 160+/-16% (p = 0.01). There was a trend (p = 0.17) toward enhanced epicardial dilation in response to acetylcholine after pravastatin treatment when compared with the baseline study. CONCLUSIONS: Our study demonstrates significant improvement in coronary resistance artery endothelial function after 6 months of cholesterol lowering with pravastatin in six subjects presenting with chest pain who were found to have normal coronary arteriograms. A trend toward improved epicardial vasomotion was also observed.     

Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients

OBJECTIVES: We compared the effects of perindopril and losartan on endothelium-dependent coronary vasomotor and fibrinolytic function. BACKGROUND: The renin-angiotensin system regulates the vascular fibrinolytic balance. However, the effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on coronary fibrinolytic function have not been compared in hypertensive patients. METHODS: Forty-five patients with hypertension were randomly assigned to three groups: 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group). Graded doses of bradykinin (BK) (0.2, 0.6, and 2.0 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. RESULTS: Bradykinin induced dose-dependent increases in CBF in all groups. The increases in CBF induced by BK in the perindopril and losartan groups were significantly greater than those in the control group. Net coronary tissue-type plasminogen activator (t-PA) release was enhanced by BK in all groups, and the increase in the perindopril group was greater than that in the losartan and control groups. Bradykinin did not alter plasminogen activator inhibitor type 1 levels in any of the groups. CONCLUSIONS: Perindopril and losartan similarly augment BK-induced coronary vasodilation. Perindopril may have a greater potential to enhance the BK-induced coronary release of t-PA than losartan.     

Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina.

It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA.     

Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors

OBJECTIVES: The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK. BACKGROUND: Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied. METHODS: Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). RESULTS: Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group. CONCLUSIONS: Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.     

Low serum adiponectin is associated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease

Decrease in adiponectin level, a common feature in patients with type 2 diabetes mellitus, is considered to predict cardiovascular events. Elevated oxidized low-density lipoprotein (oxLDL), formed within the arterial wall, is commonly seen as part of the atherogenic profile. We investigated the association of adiponectin and oxLDL in 58 patients with type 2 diabetes mellitus and ischemic coronary artery disease. In addition to adiponectin, the serum lipid profile (including oxLDL), plasminogen activator inhibitor 1, high-sensitivity C-reactive protein, and whole-body glucose uptake determined by euglycemic-hyperinsulinemic clamp were evaluated. The average adiponectin level was 7.1 +/- 3.5 microg/mL and was higher in female than in male patients (P = .011). Adiponectin level correlated with whole-body glucose uptake (P = .037) and high-density lipoprotein (HDL) cholesterol concentration (P = .007) and was inversely associated with oxLDL (P = .005), triglycerides (P = .010), and plasminogen activator inhibitor 1 (P = .004). No association was found between adiponectin and high-sensitivity C-reactive protein or LDL cholesterol levels. In multiple linear regression analysis, adiponectin contributed to oxLDL concentration, whereas total cholesterol, LDL and HDL cholesterol, and triglycerides did not. In conclusion, our results suggest that low adiponectin concentration indicates increased oxidative state in the arterial wall, which further supports previous data on the role of adipose tissue in atherogenesis.     

The predictive power of low-density lipoprotein cholesterol for coronary calcification

Background: Chronic elevation of low-density lipoprotein cholesterol is a major risk factor for developing atherosclerosis. The purpose of this study was to examine the correlation and predictive power of low-density lipoprotein cholesterol for calcified atheromatous disease as measured by electron beam computed tomography. Methods: Six-thousand and ninety-three subjects underwent electron beam computed tomography of their coronary arteries, serum lipid testing, body fat determination and assessment of health status by questionnaire. Predictive power of low-density lipoprotein cholesterol for calcified atherosclerotic plaque was determined by correlations and multivariate logistic regression. Results: The correlation between low-density lipoprotein cholesterol and calcified plaque score was very modest (r=0.055, P<0.001). There was a trend toward increasing calcified plaque with increasing levels of low-density lipoprotein cholesterol. Multivariate logistic regression revealed that low-density lipoprotein cholesterol is a modest but significant predictor of calcified coronary plaque. After adjusting for age, gender and high-density lipoprotein cholesterol, the risk of having any calcified plaque was 1.05-times higher for each 10 mg/dl increase in low-density lipoprotein cholesterol (P<0.001). Individuals with a low-density lipoprotein cholesterol level above 160 mg/dl had a 62% increase in odds for the presence of calcified plaque. Conclusions: Low-density lipoprotein cholesterol is weakly correlated with and predictive of calcified atherosclerotic plaque burden as measured by electron beam computed tomography. Higher levels of low-density lipoprotein cholesterol are associated with increased risk for the presence of calcified atheromas.     

Angiotensin-converting enzyme insertion/deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin.

The aim of this study was to assess the relationship between the angiotensin converting enzyme gene (ACE) genotype and endothelium-dependent coronary vasomotor and fibrinolytic activity. The ACE DD genotype has been reported to be a risk factor for myocardial infarction. However, the mechanism is unknown. The fibrinolytic and renin-angiotensin systems are linked via ACE at the vascular beds. We studied 73 patients (II: n=24; ID: n=37; DD: n=12) who underwent diagnostic cardiac catheterization. Graded doses of bradykinin (BK) (0.2, 0.6, 2.0 microg/min) and acetylcholine (30,100 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). Coronary release of tPA antigen was determined as a CS-Ao gradientXCBFX[(100-hematocrit) / 100]. ACE genotypes were determined using polymerase chain reaction. The ACE genotype did not appear to affect coronary macro- and microvascular responses induced by BK or acetylcholine. Coronary tissue plasminogen activator (tPA) release induced by BK was depressed in subjects with the ACE DD genotype. ACE levels in the DD genotype were significantly higher than those in the ID or II genotype. In all of the subjects, there was a significant negative correlation between the serum level of ACE activity and net coronary tPA release in response to BK at 0.6 microg/min. In conclusions, the DD genotype of the ACE gene impairs the coronary release of tPA induced by BK.     

Dyslipoproteinemia in systemic lupus erythematosus. Effect of corticosteroids

The increased incidence of atherosclerotic coronary artery disease in patients with systemic lupus erythematosus (SLE) may be due to a dyslipoproteinemia caused by corticosteroid administration. To determine whether lipoprotein lipid levels are abnormal in SLE and the relation of lipoprotein levels to corticosteroid use, lipid and apolipoprotein levels were measured in 46 female patients with SLE and 30 matched control subjects. The patients with SLE had higher levels of plasma triglyceride (134 versus 73 mg/dl; p less than 0.001), cholesterol (201 versus 168 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (121 versus 94 mg/dl; p less than 0.001) than control subjects. The levels of high-density lipoprotein cholesterol, high-density lipoprotein subfraction 3 cholesterol, and apolipoprotein Al were similar in the two groups, but high-density lipoprotein subfraction 2 cholesterol was lower in the patients with SLE (10.2 versus 18.2 mg/dl; p less than 0.001). When patients with SLE treated with prednisone (n = 32) were compared to patients with SLE not treated with prednisone (n = 14), the former had higher triglyceride (158 versus 87 mg/dl; p less than 0.001), cholesterol (214 versus 170 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (130 versus 103 mg/dl; p less than 0.001) levels. The patients with SLE not treated with prednisone had lipid levels similar to those in control subjects except that high-density lipoprotein cholesterol was lower (49.7 versus 59.0 mg/dl; p less than 0.05). The daily prednisone dosage in the treated patients with SLE correlated with levels of cholesterol (r = 0.38, p less than 0.02), high-density lipoprotein cholesterol (r = 0.40, p less than 0.02), and high-density lipoprotein subfraction 3 cholesterol (r = 0.47, p less than 0.01). Thus, female patients with SLE have a dyslipoproteinemia of the type that would place them at an increased risk for coronary artery disease. Corticosteroids, used in the treatment of SLE, seem to play a role in the pathogenesis of the observed lipoprotein abnormalities.     

Sirolimus-eluting stent implantation aggravates endothelial vasomotor dysfunction in the infarct-related coronary artery in patients with acute myocardial infarction.

OBJECTIVES: This study examined whether sirolimus-eluting stent (SES) implantation may affect endothelial vasomotor dysfunction in resistance and epicardial infarct-related coronary arteries in acute myocardial infarction (AMI). BACKGROUND: Myocardial ischemia-reperfusion causes endothelial injury entirely in the vasculature of the infarct-related coronary artery. Sirolimus-eluting stent implantation inhibits re-endothelialization at the site of stenting. METHODS: This study included 29 patients with a first AMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy using a SES (n = 13) or bare-metal stent (BMS) (n = 16). The diameter of the epicardial segment distal to the site of SES deployment and coronary blood flow in the LAD in response to an intracoronary infusion of acetylcholine were measured at 2 weeks after AMI. Levels of vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunoadsorbent assay in plasma obtained from the aortic root (AO) and the anterior interventricular vein (AIV) in all patients. RESULTS: The epicardial coronary artery was more severely constricted in response to acetylcholine in the SES than in the BMS group. The increase in coronary blood flow in response to acetylcholine was lower in the SES than in the BMS group. Vascular endothelial growth factor levels in the AIV were significantly lower than in the AO in the SES group but not in the BMS group. CONCLUSIONS: During the course of AMI, SES implantation adversely affects endothelium-dependent vasomotor function in resistance and epicardial coronary arteries after the ischemia-reperfusion in association with a reduction in myocardial VEGF secretion.     

Higher level of plasma cholesteryl ester transfer activity from high-density lipoprotein to Apo B-containing lipoproteins in subjects with angiographically detectable coronary artery disease

Background and hypothesis: Plasma high-density lipoprotein cholesterol (HDL-C) levels correlate inversely with the incidence of coronary artery disease. In order to ascertain whether the transfer activity is related to coronary atherosclerosis, we studied plasma cholesteryl ester transfer activity (CETA) from HDL to apo B-containing lipoproteins in a consecutive series of 64 Japanese men aged <60 years who had undergone diagnostic coronary angiography. Methods: The subjects were divided into two groups: those who had ≥50% luminal stenosis in one or more coronary arteries (Group 1) and those who had <50% stenosis (Group 2). Results: CETA was 20.8±6.0%/2h in 38 subjects in Group 1. significantly higher than 17.4±6.9%/2h in 26 subjects in Group 2(p<0.05). Plasma HDL-C levels in Group 1 were significantly lower than those in Group 2(p<0.05). CETA correlated inversely with HDL-C levels (r = ?0.46, p<0.001). Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and Lp(a) levels did not differ significantly between the two groups. There was no significant correlation between CETA and either LDL-C or TG levels. Conclusion: Results suggest that high CETA is realted to low plasma HDL-C levels and may lead to the development of coronary atherosclerosis. Also, CETA was independent of plasma LDL-C or TG levels.     

Reducing oxidized lipids to prevent cardiovascular disease

Despite significant success in reducing plasma cholesterol, especially low-density lipoprotein cholesterol, risks for cardiovascular disease (CVD) complications remain. Among these risks are circulating levels of oxidative modified lipoproteins, primarily oxidized low-density lipoproteins (oxLDL). The evidence supporting oxLDL as a potential target for therapeutic management to reduce metabolic complications and CVD events is reviewed in this report.     

Association between isolated hypercholesterolemia, isolated hypertriglyceridemia and coronary artery disease in south Indian type 2 diabetic patients

Very high prevalence rates of coronary artery disease have been reported among Indians. The aim of this study was to determine the relative importance of isolated hypercholesterolemia, isolated hypertriglyceridemia, isolated high low-density lipoprotein and isolated low high-density lipoprotein in coronary artery disease among South Indian type 2 diabetic subjects. The study group comprised of 17,885 type 2 diabetic patients attending our institute. A history of documented myocardial infarction was considered as the diagnostic criteria for coronary artery disease. Isolated hypercholesterolemia was defined as serum cholesterol over 200 mg/dL with normal serum triglyceride levels (< or = 200 mg/dL); isolated hypertriglyceridemia was defined as serum triglyceride level over 200 mg/dL with normal serum cholesterol levels (< or = 200 mg/dL). Isolated low high-density lipoprotein was defined as one below 35 mg/dL with normal serum triglyceride levels. Isolated high low-density lipoprotein cholesterol was defined as one over 150 mg/dL with normal serum triglyceride levels. Normolipidemia was defined as serum cholesterol and serum triglyceride both upto 200 mg/dL, high-density lipoprotein 35 mg/dL or above and low-density lipoprotein upto 150 mg/dL. The prevalence of coronary artery disease was significantly high among patients with isolated hypercholesterolemia (4.1%; p < 0.001), isolated high low-density lipoprotein (4.5%; p < 0.001) and isolated low high-density lipoprotein (3.9%; p = 0.005) compared to normolipidemic individuals (2.8%), but not in those with isolated hypertriglyceridemia (3.4%). The odds ratios for coronary artery disease increased with each quartiles of isolated cholesterol, isolated low-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein ratio and reached statistical significance in the last quartile (p < 0.05). There was no significant increase in the odds ratios for coronary artery disease in relation to quartiles of isolated triglycerides. For isolated low high-density lipoprotein, when the last quartile was taken as the reference, the odds ratio for coronary artery disease in the first quartile reached statistical significance (p = 0.03). Multivariate regression analysis revealed age (odds ratio 1.06; p < 0.001), male sex (odds ratio 1.7; p < 0.001), hypercholesterolemia (odds ratio 1.26; p = 0.07) and high low-density lipoprotein levels (odds ratio 1.22; p = 0.043) to be strongly associated with coronary artery disease. Among South Indian type 2 diabetic subjects, serum isolated hypercholesterolemia and high low-density lipoprotein cholesterol but not isolated hypertriglyceridemia appear to be associated with coronary artery disease.     

Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins

The distribution of apolipoprotein C-III (apoC-III) between high-density lipoprotein (HDL) and apoB-containing lipoproteins has been used in lipid-lowering angiographic trials to establish a link between impaired triglyceride (TG)-rich lipoprotein (TRL) metabolism and the progression of coronary artery disease. To investigate the extent to which plasma lipoprotein apoC-III levels reflect the presence in plasma of potentially atherogenic remnant lipoproteins, we studied 4 groups of subjects: (1) normolipidemic (NL, n = 10), (2) hypercholesterolemic (HC, type IIa, low-density lipoprotein cholesterol [LDL-C] > 3.4 mmol/L, n = 10), (3) hypertriglyceridemic (HTG, type IV, TG > 2.3 mmol/L, n = 10), and (4) combined hyperlipidemic (CHL, type IIb, TG > 2.3 mmol/L, LDL-C > 3.4 mmol/L, n = 10). The apoC-III level was measured in plasma lipoproteins separated either by density (ultracentrifugation) or by size (fast protein liquid chromatography [FPLC]), and was compared with 4 parameters reflecting remnant lipoprotein levels (ie, very-low-density lipoprotein cholesterol [VLDL-C], intermediate-density lipoprotein cholesterol [IDL-C], remnant-like particle cholesterol [RLP-C], and intermediate-sized lipoprotein [ISL] apoE). Our results demonstrate that (1) increased amounts of apoC-III associated with plasma VLDL, TRL, or apoB-containing lipoproteins (LpB), as well as increased levels of TRL remnant lipoproteins, are a characteristic of HTG patients rather than patients with increased LDL, and (2) plasma levels of apoC-III in VLDL, TRL, or LpB, as well as the HDL apoC-III to LpB apoC-III ratios, are strongly correlated with circulating levels of TRL, although these apoC-II parameters more closely reflect the balance between TRL TG production and lipolysis than the extent of plasma TRL remnant accumulation.     

High remnant lipoprotein levels in patients with variant angina

BACKGROUND: Dyslipidemia with increased oxidative stress but without elevation of low-density lipoprotein cholesterol has been recently implicated in the pathogenesis of coronary vasospasm. HYPOTHESIS: Disordered triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary artery spasm. METHODS: Both serum remnant lipoprotein (RLP) and alpha-tocopherol levels were determined in 18 patients with the active stage of variant angina (VA), in 16 patients with the inactive stage of variant angina (IVA), and in 19 control subjects (CONTROL). RESULTS: The RLP levels were significantly (p < 0.05) higher in VA (6.4 +/- 2.7 mg/dl) than in IVA (4.4 +/- 1.5 mg/dl). In contrast, alpha-tocopherol levels were significantly lower in VA than that in CONTROL. Serum trigyceride levels were not significantly different among the study groups, although serum high-density lipoprotein cholesterol levels were significantly lower in VA than in CONTROL. Smoking was significantly (p < 0.05) more prevalent in VA (72%) than in IVA (25%) and CONTROL (37%). Serum RLP levels correlated positively with triglyceride levels (R = 0.73) and correlated inversely with alpha-tocopherol levels (R = -0.31) significantly in all study subjects. CONCLUSIONS: Patients with active stage of variant angina had higher RLP levels than inactive patients with variant angina and lower alpha-tocopherol levels than control subjects. Disordered triglyceride-rich lipoprotein metabolism with increased oxidative stress appears to be linked to the activity of coronary vasospasm, suggesting a possible role in its pathogenesis.     

Evaluation of improved coronary flow velocity reserve using transthoracic Doppler echocardiography after single LDL apheresis

The purpose of this study was to clarify whether coronary flow velocity reserve (CFVR), evaluated by adenosine 5'-triphosphate-induced hyperemia, is improved by single low-density lipoprotein (LDL) apheresis. Lipid lowering therapy is known to improve endothelium-dependent vasodilatation in forearm or coronary resistant vessels. However, few reports have studied the effect of acute LDL reduction on CFVR. Methods: Seven patients with familial hypercholesterolemia and significant coronary stenosis except in the left anterior descending artery (LAD) were enrolled in this study. Coronary flow velocity reserve was estimated before and after LDL apheresis using transthoracic Doppler echocardiography (TTDE), which detects the flow velocity at the distal site of the LAD. Although the averaged diastolic peak velocity (ADPV) during ATP-induced hyperemia was similar before and after LDL apheresis, the ADPV at baseline decreased from 30.69 to 25.56 cm/s, resulting in an increased CFVR from 1.78 to 2.10 (P < 0.001). Plasma bradykinin and 6 keto PGF1alpha increased while fibrinogen and plasma viscosity decreased after apheresis. Single LDL apheresis improves CFVR according to TTDE analysis because of the decreasing ADPV at baseline, which is thought to be induced by epicardial coronary artery dilatation and improved microvessel function. This is the result of various factors, such as changes in plasma LDL cholesterol, bradykinin and PGI2 levels with LDL apheresis.     

Effect of pravastatin on coronary plaque volume

A volumetric analysis by 3-dimensional intravascular ultrasound revealed that lipid-lowering therapy with pravastatin significantly reduced coronary plaque volume. The changes in plaque volume were inversely correlated with the changes in plasma levels of high-density lipoprotein cholesterol but not with changes in levels of total cholesterol or low-density lipoprotein cholesterol.     

不同冠状动脉病变程度冠心病患者血浆脂联素水平及其相关性研究

目的:了解不同冠状动脉(冠脉)病变程度的冠心病(CHD)患者血浆脂联素(APN)水平及其与胰岛素抵抗(IR)、血糖(FPG)、血脂、血压、肥胖、冠脉病变程度的关系.方法:选取冠脉造影检查者共128例作为研究对象,根据冠脉病变支数,分为单支病变组32例、双支病变组30例、多支病变组32例和冠脉造影正常的对照组34例.测量血压、身高、体重、腰围(WC)和臀围.采空腹静脉血,测定血浆APN、胰岛素(FINS)、FPG、TC、TG、HDL-C、LDL-C、载脂蛋白A1(apo-A1)和载脂蛋白B(apo-B).计算体质指数(BMI)、腰臀比(WHR)、胰岛素敏感指数(ISI)和Gensini积分.结果:CHD各组血浆APN水平低于对照组(P＜0.01).血浆APN水平与收缩压、舒张压、WC、BMI、WHR、TC、LDL-C、FINS、Gensini积分均呈负相关(P＜0.05或0.01),与ISI呈正相关(P＜0.01).均衡年龄、血压、FPG、血脂、肥胖等影响后,APN仍与Gensini积分、FINS、ISI存在相关性(P＜0.01).回归分析显示,ISI、WC和Gensini积分是影响血浆APN水平的独立因素.结论:CHD患者血浆APN水平降低并与冠脉病变程度密切相关,与IR、血脂、血压和肥胖存在一定的相关性.