Normocholesterolemic Patients Research Articles

Association between plasma lipoprotein(a) and endothelial dysfunction in normocholesterolemic and non-diabetic patients with angiographically normal coronary arteries.

The present study was designed to examine whether elevated levels of lipoprotein(a) (Lp(a)) are related to the impairment of the endothelium-dependent vasoresponse to acetylcholine (ACh) in normocholesterolemic and non-diabetic human normal coronary arteries. ACh (30 microg) was injected into the left main coronary artery of 31 patients (serum low-density cholesterol <160mg/dl and fasting plasma glucose <126mg/dl) with angiographically normal coronary arteries, and the relation between diameter change and lipid levels was analyzed. The mean diameter change of all coronary segments examined (segments 6, 8, 11 and 13) was reduced by 14.6+/-26.5% in response to ACh, but increased by 23.3+/-6.0% in response to nitroglycerin, suggesting endothelial dysfunction in those arteries. The mean diameter change of the left anterior descending artery or left circumflex artery in each patient was negatively correlated only with the level of Lp(a). Stepwise multiple regression analysis also revealed that only Lp(a) among the lipids showed significant correlation with impaired vasodilation (p=0.033). These findings suggest that elevated levels of plasma Lp(a) might be a strong predictor of endothelial dysfunction in normocholesterolemic and non-diabetic subjects.

Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men

The effect of high-dose atorvastatin treatment in normocholesterolemic patients was studied to answer the following questions: Is there a detectable benefit on endothelial function and inflammation within 24 to 48 hours after initiation of treatment 1 Aronow H.D. Topol E.J. Roe M.T. Houghtaling P.L. Wolski K.E. Lincoff A.M. Harrington R.A. Califf R.M. Ohman E.M. Kleiman N.S. et al. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes an observational study. Lancet. 2001; 357: 1063-1068 Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar , 2 Dupuis J. Tardif J.C. Cernacek P. Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation. 1999; 99: 3227-3233 Crossref PubMed Scopus (512) Google Scholar , 3 Schwartz G.G. Olsson A.G. Ezekowitz M.D. Ganz P. Oliver M.F. Waters D. Zeiher A. Chaitman B.R. Leslie S. Stern T. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes the MIRACL study: a randomized controlled trial. JAMA. 2001; 285: 1711-1718 Crossref PubMed Google Scholar ? Does atorvastatin alter vascular function independent of serum cholesterol? And finally, is there a deleterious effect of acute statin withdrawal with respect to vascular function and inflammation 4 Thomas M. Mann J. Increased thrombotic vascular events after change of statin. Lancet. 1998; 352: 1830-1831 Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar , 5 Laufs U. Endres M. Custodis F. Gertz K. Nickenig G. Liao J.K. Böhm M. Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000; 102: 3104-3110 Crossref PubMed Scopus (255) Google Scholar ?

Apo(B)-dependent dyslipidemic phenotypes in type 1 diabetic patients

Background: The prevalence of apo(B)-dependent dyslipidemic phenotypes, which are associated with cardiovascular disease, is increased in normocholesterolemic type 2 diabetic patients. Our aim was to determine the impact of including apo(B) in the evaluation of normocholesterolemic type 1 diabetic patients. Methods: A total of 123 type 1 diabetic patients (47% male, age 36.6±12.5 years) were included. The apo(B) cut-off point (1.14 g/l) was obtained from a group of 53 normolipidemic control subjects of similar age and gender distribution; for low density lipoprotein cholesterol (LDLc), triglycerides, and high density lipoprotein cholesterol (HDLc), we used the cut-off points recommended by the National Cholesterol Education Program. LDLc was determined by ultracentrifugation or Friedewald’s equation, depending on triglyceride concentrations, and apo(B) by immunoturbidimetry. Results: A total of 113 (92%) type 1 diabetic patients were normocholesterolemic, and 13% of these were dyslipidemic. The frequency of hyperapo(B) was similar in normocholesterolemic patients and controls (6.2 vs. 9.4%, respectively). Diabetic patients with hyperapo(B) had poorer glycemic control, higher total cholesterol, triglycerides, and LDLc, and a lower HDLc and LDLc/apo(B) ratio. Conclusions: Unlike type 2 diabetes, type 1 diabetes is not associated with an increased prevalence of hyperapo(B)-dependent dyslipidemic phenotypes. Thus, only in patients with poor glycemic control who display other components of diabetic dyslipidemia, typical for type 2 diabetes, does determining apo(B) concentrations provide additional information in type 1 diabetes.

Impairment of endothelial function after a high-fat meal in patients with coronary artery disease.

To determine the effect of postprandial lipid changes on endothelial function in patients with coronary artery disease (CAD) after a high-fat meal. We studied 50 CAD patients and 25 control participants, who were all normocholesterolemic. Flow-mediated vasodilatation of the brachial artery was evaluated by the high-resolution ultrasound technique before and after a single high-fat meal (800 calories; 50 g fat). Postprandial serum triglyceride level increased significantly at 2-7 h and mean flow-mediated vasodilatation was impaired significantly (from 4.22 +/- 0.44 to 2.75 +/- 0.33%, P < 0.01) for 75 subjects. The increment in 2 h serum triglyceride level correlated positively with the decrement in postprandial flow-mediated vasodilatation (r = 0.459, P < 0.01). Postprandial triglyceride level was significantly higher in CAD patients than in control participants. Flow-mediated vasodilatation was significantly impaired in CAD patients (from 3.04 +/- 0.39 to 1.69 +/- 0.23%, P < 0.01) and control participants (from 6.58 +/- 0.52 to 4.87 +/- 0.19%, P < 0.05) after a high-fat meal. The impairment of flow-mediated dilatation was more severe in CAD patients (44.41%) than in control participants (25.99%, P < 0.01). Postprandial endothelium-dependent vasodilatation after a single high-fat meal was severely impaired in normocholesterolemic CAD patients and control participants. The disordered postprandial metabolism of triglyceride-rich lipoproteins may play an atherogenic role by inducing endothelial dysfunction.

Enhanced endothelium-dependent vasodilation in Fabry disease.

Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis. Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L-arginine (L-NMMA). Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036). These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.

Randomized, controlled trial of secondary prevention of coronary sclerosis in normocholesterolemic patients using pravastatin: two-year follow-up of the prevention of coronary sclerosis study

Background: Reducing serum total cholesterol (TC) levels using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in hypercholesterolemic patients has been shown to reduce the incidence of complications of coronary heart disease (CHD). However, few data are available on the potential benefit of reductions in serum cholesterol levels in normocholesterolemic patients with coronary atherosclerosis. Objective: The Prevention of Coronary Sclerosis Study is a single-center study designed to assess the effect of treatment with the HMG-CoA reductase inhibitor pravastatin on progression and regression of angiographically documented coronary atherosclerosis in normocholesterolemic patients with CHD. Methods: A total of 329 patients aged <70 years with CHD were enrolled and classified into 1 of 3 groups based on serum TC level: group 1, TC ≥220 mg/dL; group 2, TC 180–219 mg/dL; and group 3, TC <180 mg/dL. Patients in group 2 were randomized to 1 of 2 subgroups, 2a or 2b. Patients in groups 1 and 2a were given pravastatin 10 mg/d; patients in groups 2b and 3 did not receive cholesterol-lowering drugs. The subsequent coronary events of patients were followed for 2 years and reexamined by coronary angiography (CAG). Both baseline and follow-up CAGs were analyzed by quantitative coronary arteriography at a central laboratory. Results: Decreases in both mean segment diameter (MSD) and minimum obstruction diameter (MOD) in group 2a were significantly less than those in the control group 2b ( P = 0.015 and P = 0.023, respectively). The effects on MSD and MOD in group 2a and the low-cholesterol reference group 3 were similar. The incidence of clinical events was 8.9%, 3.7%, 12.1%, and 10.0% in groups 1, 2a, 2b, and 3, respectively, with no significant differences in rates between groups 2a and 2b. Conclusion: The results of this study suggest that cholesterol-lowering therapy with pravastatin may prevent progression of coronary atherosclerosis in normocholesterolemic patients with CHD.

Effect of cardiopulmonary bypass on plasma levels of lipoprotein (a) in hypercholesterolemic patients.

Increments of lipoprotein (a) (Lp (a)) concentration during cardiopulmonary bypass (CPB) have not been justified in the literature yet. We have investigated whether Lp (a) levels remain constant or increase during CPB and if high plasma levels of low density lipoprotein (LDL; containing apolipoprotein (apo) B) in hypercholesterolemic patients affect the assembly of Lp (a) (containing apoB: Apo (a)). In this study, the change in plasma lipid and lipoprotein levels of 40 patients with hypercholesterolemia and 40 patients who have normal cholesterol values were determined and compared during CPB, and in the postoperative early stage. In our study, lipid and lipoproteins, except Lp (a), showed a falling trend and paradoxically, Lp (a) statistically showed a significant rising trend, like the acute phase reactant in two groups (p=0.011 for LDL, p=0.016 for high density lipoprotein (HDL) and p<0.001 for the others, in 80 patients). Concentrations of Lp (a) in plasma increased more sharply in the hypercholesterolemic group than the normocholesterolemic group during CPB. This difference was significant at the 60th minute of cardiopulmonary bypass with a nonparametric test (p<0.05 Mann-Whitney U test). High density lipoprotein values showed more decline in the hypercholesterolemic group patients than in the normocholesterolemic group patients (p<0.05). In conclusion, lipoprotein (a) levels increased more pronounced in patients with hypercholesterolemia during CPB. On the other hand, high LDL levels in hypercholesterolemic patients accelerated Lp(a)formation in the acute phase.

Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels

Background Limited information is available as to whether there is a difference in the association of lipid and fibrinolytic variables with coronary artery disease according to the presence or absence of elevated serum total cholesterol. We examined the levels of various lipid and fibrinolytic variables including remnant-like particle cholesterol (RLP-C). RLP-C is a recently established simple assay method for the estimation of triglyceride-rich lipoprotein remnants. Methods and Results Levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein (a), RLP-C, uric acid, blood glucose, tissue plasminogen activator, tissue plasminogen activator inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. Of these 208 patients, 57 were hypercholesterolemic (≥220 mg/dL) and 151 were normocholesterolemic. HDL-C showed significant differences between patients with and those without angiographically determined coronary artery stenosis in both hypercholesterolemic and normocholesterolemic patients ( P =.0025 and P =.0003, respectively). Both RLP-C and uric acid showed significant differences only in the normocholesterolemic subgroup ( P =.0006 and P = .0060, respectively). This difference in uric acid was not significant by multivariable analysis. The ratio of RLP-C/HDL-C was demonstrated to be highly significantly ( P <.0001) associated with coronary artery stenosis in patients with normal total cholesterol, whereas there was no statistically significant association in the hypercholesterolemic patient subgroup. Conclusions Our current study disclosed that RLP-C levels are strongly associated with coronary artery disease, especially in patients with normal total cholesterol levels. Moreover, RLP-C/HDL-C ratio may be even more significantly associated with the presence of coronary artery stenosis in normocholesterolemic patients.

Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels.

Limited information is available as to whether there is a difference in the association of lipid and fibrinolytic variables with coronary artery disease according to the presence or absence of elevated serum total cholesterol. We examined the levels of various lipid and fibrinolytic variables including remnant-like particle cholesterol (RLP-C). RLP-C is a recently established simple assay method for the estimation of triglyceride-rich lipoprotein remnants. Levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), RLP-C, uric acid, blood glucose, tissue plasminogen activator, tissue plasminogen activator inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. Of these 208 patients, 57 were hypercholesterolemic (> or =220 mg/dL) and 151 were normocholesterolemic. HDL-C showed significant differences between patients with and those without angiographically determined coronary artery stenosis in both hypercholesterolemic and normocholesterolemic patients (P =.0025 and P =.0003, respectively). Both RLP-C and uric acid showed significant differences only in the normocholesterolemic subgroup (P =.0006 and P =.0060, respectively). This difference in uric acid was not significant by multivariable analysis. The ratio of RLP-C/HDL-C was demonstrated to be highly significantly (P <.0001) associated with coronary artery stenosis in patients with normal total cholesterol, whereas there was no statistically significant association in the hypercholesterolemic patient subgroup. Our current study disclosed that RLP-C levels are strongly associated with coronary artery disease, especially in patients with normal total cholesterol levels. Moreover, RLP-C/HDL-C ratio may be even more significantly associated with the presence of coronary artery stenosis in normocholesterolemic patients.

Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients.

Apolipoprotein(B) [apo(B)] reflects the total mass of atherogenic particles (VLDL, IDL, and LDL), and its increase is associated with cardiovascular disease independently of LDL cholesterol (LDLc) levels. Apo(B) determination has been recently standardized, but attention to regional reference limits is advisable. Our aim was to analyze the frequency of dyslipidemic phenotypes, including those dependent on increased apo(B) in normocholesterolemic type 2 diabetic patients. A total of 100 consecutively seen type 2 diabetic patients (63 men, 37 women; aged 59 +/- 11 years) were included, after excluding those on lipid-lowering therapy. Apo(B) cutoff (1.1 g/l) was obtained from a group of normolipidemic (47 men, 21 women) control subjects, and LDLc, triglycerides, and HDL cholesterol (HDLc) cutoff points were those from the National Cholesterol Education Program guidelines. LDLc levels were obtained by ultracentrifugation if triglyceride levels were > 3.45 mmol/l; otherwise, they were calculated (Friedwald). Apo(B) levels were measured by immunoturbidimetry. Normocholesterolemia (LDLc < 4.13 mmol/l) appeared in 75 of the 100 patients, of whom 55 were normo- and 20 hypertriglyceridemic. Hyperapolipoprotein(B) [hyperapo(B)] was the most frequent lipid disorder, present in 34 (45%) of the normocholesterolemic patients (22 normo- and 12 hypertriglyceridemic). Low HDLc levels were more prevalent (53%) in patients with hyperapo(B) than in the rest (24%). Hyperapo(B) was found in almost half of the normocholesterolemic type 2 diabetic patients and was frequently associated with low HDLc levels and hypertriglyceridemia. Thus, given its independent association with cardiovascular disease and that it identifies high-risk phenotypes in normocholesterolemic diabetic patients apo(B) should be used to evaluate the lipidic pattern of these patients.

Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia

Background The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of patients with heterozygous FH to characterize the premature atherosclerotic lesions by using histopathologic specimens. Methods and Results The aortic roots of 10 patients with homozygous FH, age 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic roots of 39 patients with heterozygous FH under age 60 years were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as control subjects. In addition, in 22 patients with FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 homozygotes with FH, 8 patients had aortic regurgitation demonstrated by aortography; 3 of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 heterozygotes with FH, 10 patients had aortic regurgitation shown by Doppler echocardiography, as did only 1 of the 30 control subjects ( P < .05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared with the control subjects. The surgically resected cusp specimens of aortic valves obtained from 1 homozygous and 1 heterozygous patient showed significant thickening of the cusp with foam cell infiltration. Conclusions Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating “hypercholesterolemic valvulopathy” was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes caused by hypercholesterolemia. (Am Heart J 1999;137:410-8.)

Cyclosporine plasma unbound fraction in heart and lung transplantation recipients.

To investigate the variability in the unbound fraction (fu) of cyclosporine in recipients of heart, heart-lung, and lung transplantation, cyclosporine fu was determined ex vivo in plasma by equilibrium dialysis. In a retrospective study, 260 samples of plasma (one to seven per patient) were obtained from 89 heart (86%), lung (9%), and heart-lung (5%) transplant patients. The unbound fraction (x100) of cyclosporine ranged from 0.52% to 3.94%, with an overall mean of 1.53%+/-0.375% (SD). The mean percentage unbound for individual patients ranged from 0.71% to 1.98%, giving a 2.8-fold interpatient variation. In heart transplant recipients (66 patients), the values of fu were significantly lower (p < 0.01) during more severe rejection episodes, which required antirejection treatment (endomycardial biopsy result of grade 3a and higher) than in the absence of rejection (grade 0) or during grade la rejections. The value of fu did not vary with organ transplanted (p = 0.35) or etiology of organ failure (p = 0.32). Cyclosporine fu was negatively correlated with the age of the patient (r = -0.18, p < 0.05). Correlations were not observed between fu and blood biochemical and cytologic indices. However, fu was significantly lower (p < 0.01) in hypercholesterolemic transplant recipients (1.37+/-0.52%) than in normocholesterolemic patients (1.60+/-0.63%). Administration of simvastatin resulted in a significant increase in the mean fu from 1.40+/-0.09%) to 1.82+/-0.13% (paired t test, n = 13; p < 0.01). In patients who received ketoconazole, fu was not different from controls. These findings suggest that the level of cyclosporine fu may be an important determinant of immunosuppressive activity of cyclosporine. Moreover, the variation in fu could be strongly related to the concentration of serum lipoproteins; interpretation of the results of cyclosporine monitoring thus requires consideration of the lipidemic status of the patient.

Coronary risk factors influence plaque morphology in patients with unstable angina.

The risk of plaque disruption and subsequent thrombosis in patients with unstable angina depends on the plaque type and size. Intravascular ultrasound (IVUS) was employed to illustrate the correlation between risk factors and plaque morphology in patients with unstable angina. In a prospective study of 60 of 95 patients consecutively admitted with unstable angina [41 men, aged 61.2 +/- 8.1 years (mean +/- SD)], qualitative (soft and hard plaque, thrombus, calcification, eccentricity, adaptive and constrictive remodeling) and quantitative [lumen, external elastic membrane (EEM) and plaque cross-sectional area (CSA) and plaque burden] IVUS data relating to the target lesion, and proximal and distal reference segments were analyzed and correlated with risk factors. Univariate and multivariate nominal logistic regression analyses and analyses of variance were used to determine the independent predictors for IVUS morphology. For plaque composition univariate analysis showed a younger age (< 60 years) to be a predictor for adaptive remodeling (P = 0.019), and an older age to be a predictor for constrictive remodeling (P = 0.021). Hypercholesterolemia, smoking and sex were associated with a higher frequency of thrombus (P = 0.044, 0.038 and 0.043, respectively). Multivariate analyses revealed that only younger and older ages were independent predictors for adaptive and constrictive remodeling (P = 0.039 and P = 0.045). For plaque size, univariate and multivariate analyses demonstrated that diabetes mellitus and hypercholesterolemia were independent predictors for greater plaque (13.5 +/- 5.72 versus 10.17 +/- 4.6 mm2, P = 0.015, for diabetic versus non-diabetic patients; 12.0 +/- 5.35 versus 9.03 +/- 3.76 mm2, P = 0.010, for hypercholesterolemic versus normocholesterolemic patients) and EEM CSA (17.16 +/- 5.81 versus 14.3 +/- 5.1 mm2, P = 0.033, for diabetic versus non-diabetic patients; 16.57 +/- 5.49 versus 12.25 +/- 3.8 mm2, P = 0.001, for hypercholesterolemic versus normocholesterolemic patients) at the target lesion. Hypercholesterolemia was associated with significantly greater plaque and EEM CSA in both proximal and distal reference segments. Multivariate analyses indicated that age, diabetes and hypercholesterolemia are independent predictors for plaque morphology in patients with unstable angina.

Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7alpha-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients. acids via the acidic pathway.

Impaired Myocardial Vasodilation During Hyperemic Stress With Dipyridamole in Hypertriglyceridemia

Objectives. This study sought to investigate the specific role of hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest flow ratio (MDR).Background. Reduced MDR has been reported in hypercholesterolemic patients without evidence of ischemia. However, the specific role of hypertriglyceridemia in MDR has not been studied.Methods. Fifteen nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched control subjects were studied. Myocardial blood flow (MBF) during dipyridamole administration and baseline MBF in hypertriglyceridemic patients and control subjects were measured using positron emission tomography and nitrogen-13 ammonia, after which the MDR was calculated.Results. Baseline MBF (ml/min per 100 g heart weight) in hypertriglyceridemic patients (mean ± SD 73.6 ± 24.1) did not differ significantly from that in control subjects (81.6 ± 37.2). MBF during dipyridamole loading in hypertriglyceridemic patients (198 ± 106) was significantly reduced compared with that in control subjects (313 ± 176, p < 0.05), as was the MDR (2.71 ± 1.07 vs. 3.73 ± 1.14, respectively, p < 0.05). Spearman rank-order correlation analysis showed a significant relation between plasma triglyceride concentration and MDR (r = −0.466, asymptotic SE 0.157, p = 0.0125); however, no such significant relation was seen between total plasma cholesterol concentration and MDR (r = −0.369, asymptotic SE 0.130, p = 0.059).Conclusions. Impaired myocardial vasodilation was suggested in hypertriglyceridemic patients without symptoms and signs of ischemia.

High-density lipoprotein particles are large in patients with variant angina.

Dyslipidemia in patients with coronary vasospasm may be characterized by low level of high-density lipoprotein (HDL)-cholesterol as well as apolipoprotein (apo) A-I but not high level of low-density lipoprotein-cholesterol. This study sought to examine the HDL particle size in patients with variant angina. The HDL particle size was examined by analyzing serum lipid levels in 38 patients with variant angina to compare with those of 40 control subjects and 30 normocholesterolemic patients with stable effort angina. Also, actual HDL size distribution was assessed by electrophoresis. The HDL-cholesterol, apoA-I and apoA-II levels were all lower (P < 0.01 for each) in patients with variant angina and patients with stable effort angina as compared with control subjects. The apoA-II level was lower (P < 0.01) in patients with variant angina than in patients with stable effort angina. The apoA-I/apoA-II ratio was lower (P < 0.01) in patients with stable effort angina, but not in patients with variant angina as compared with control subjects. In contrast, the HDL-cholesterol/apoA-I ratio was higher in patients with variant angina than in control subjects (P < 0.01) and also patients with stable effort angina (P < 0.01). The slope of the regression line, comparing HDL-cholesterol and apoA-I levels, was greater in patients with variant angina than in control subjects (P < 0.05) and patients with stable effort angina (P < 0.05), suggesting an increase in larger HDL particles. Native polyacrylamide gel electrophoresis revealed that HDL particles in patients with variant angina were skewed towards larger sizes compared with control subjects (P < 0.01) and patients with stable effort angina (P < 0.01). The abnormal serum lipid values were normalized in the patients with variant angina after the medical treatment and inactivation of the coronary spasm. High HDL-cholesterol/apoA-I levels associated with low serum HDL-cholesterol and apoA-I levels were characteristic in patients with variant angina, in whom HDL particles were large, cholesterol-rich and possibly malfunctioning.

Reduced Myocardial Flow Reserve in Non–Insulin-Dependent Diabetes Mellitus

Objectives. We analyzed myocardial flow reserve (MFR) in patients with non–insulin-dependent (type II) diabetes mellitus (NIDDM) without symptoms and signs of ischemia.Background. Diminished MFR in diabetes has been suggested. However, it remains controversial whether MFR is related to glycemic control, mode of therapy or gender in NIDDM.Methods. Myocardial blood flow (MBF) was measured at baseline and during dipyridamole loading in 25 asymptomatic, normotensive, normocholesterolemic patients with NIDDM and 12 age-matched control subjects by means of positron emission tomography and nitrogen-13 ammonia, after which MFR was calculated.Results. Baseline MBF in patients with NIDDM ([mean ± SD] 74.0 ± 24.0 ml/min per 100 g body weight) was comparable to that in control subjects (73.0 ± 17.0 ml/min per 100 g). However, MBF during dipyridamole loading was significantly lower in patients with NIDDM (184 ± 99.0 ml/min per 100 g, p < 0.01) than in control subjects (262 ± 120 ml/min per 100 g), as was MFR (NIDDM: 2.77 ± 0.85; control subjects: 3.8 ± 1.0, p < 0.01). A significantly decreased MFR was seen in men (2.35 ± 0.84) compared with women with NIDDM (3.18 ± 0.79, p < 0.05); however, no significant differences were found in terms of age, hemoglobin a1c and baseline MBF. MFR was comparable between the diet (2.78 ± 0.80) and medication therapy groups (2.76 ± 0.77) and was inversely correlated with average hemoglobin A1c for 5 years (r = −0.55, p < 0.01) and fasting plasma glucose concentration (r = −0.57, p < 0.01) but not age or lipid fractions.Conclusions. Glycemic control and gender, rather than mode of therapy, is related to MFR in NIDDM.

Effect of Pravastatin (10 mg/day) on Progression of Coronary Atherosclerosis in Patients With Serum Total Cholesterol Levels from 160 to 220 mg/dl and Angiographically Documented Coronary Artery Disease

To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a pravastatin (10 mg/day) group (n = 45) and control group (n = 45) in a 2-year study. The proportions of patients with progression (an increase of ≥15% in percent stenosis) and regression (a decrease of ≥15% in percent stenosis) of coronary atherosclerosis were compared between the 2 groups. Of 90 patients, 80 (89%) had a final angiogram: the pravastatin (n = 39) and control group (n = 41). Percent changes in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels were significantly greater in the pravastatin group than in the control group (total cholesterol −11 ± 12% vs 3 ± 15%, p <0.01; low-density lipoprotein cholesterol −18 ± 16% vs 4 ± 21%, p <0.01; apoprotein B −5 ± 20% vs 6 ± 20%, p <0.05). The proportion of patients with progression of coronary atherosclerosis was significantly smaller in the pravastatin group than in the control group (21% vs 49%, p <0.05). The proportion of patients with disease regression did not differ in the 2 groups (3% vs 2%, p = NS). In conclusion, this study indicates that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis even in normocholesterolemic patients with established CAD.To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a 2-year study: the pravastatin (10 mg/day) group (n = 45) and the control group (n = 45). Results of this study indicate that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis stenosis even in normocholesterolemic patients with established CAD.

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholsterolemia (<1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (<1 mmol/liter). J. Clin. Apheresis 12:110–115, 1997. © 1997 Wiley-Liss, Inc.