High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography.

BACKGROUND: Although high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) are well-established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). MATERIAL AND METHODS: Five thousand six hundred forty-one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of >or= 70%. Coronary angiograms were graded as one-, two- or three-vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non-CAD. RESULTS: HDL-C (60.3 +/- 18.5 vs. 51.9 +/- 15.3 mg dL(-1); P < 0.001) was higher and CRP was lower (0.65 +/- 1.68 vs. 1.02 +/- 2.38 mg dL(-1); P < 0.001) in non-CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65.2 +/- 10.5 years vs. 59.9 +/- 11.4 years), more often diabetics (19.2% vs. 10.6%) and hypertensives (79.2% vs. 66.0%) and included more smokers (18.8% vs. 16.5%) (all P < 0.005). Low-density lipoprotein cholesterol (124.5 +/- 38.3 vs. 126.0 +/- 36.3 mg dL(-1); P = NS) was similar in overall CAD and non-CAD patients with more statin users (43.4% vs. 27.9%; P < 0.001) among CAD patients. Comparing non-CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL-C and CRP remained independently associated with the prevalence of CAD. In addition, HDL-C is also a potent predictor for the severity of CAD. CONCLUSIONS: In this large consecutive patient cohort, HDL-C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL-C is an even stronger predictor for CAD than some other major classical risk factors.

Robotic totally endoscopic coronary artery bypass: program development and learning curve issues.

BACKGROUND: The introduction of new procedures in heart surgery is a critical phase that includes learning curves and the risk of increased mortality or morbidity. Totally endoscopic coronary artery bypass grafting using robotic techniques represents such an innovative procedure. The aim of this report is to demonstrate the safe introduction of totally endoscopic coronary artery bypass grafting using a stepwise and modular approach. METHODS: From June 2001 until December 2002, 50 procedures were performed using the da Vinci telemanipulator system. After baseline training the following procedure modules were carried out in a stepwise manner: robotically assisted endoscopic left internal thoracic artery harvesting and completion of the procedure as conventional coronary artery bypass grafting, minimally invasive direct coronary artery bypass, or off-pump coronary artery bypass (n = 19), robotically assisted suturing of left internal thoracic artery to left anterior descending anastomoses during conventional coronary artery bypass grafting (n = 15), totally endoscopic coronary artery bypass grafting on the arrested heart using remote access perfusion and aortic endocclusion coronary bypass grafting (n = 15). One patient was excluded intraoperatively from a robotic procedure due to pleural adhesions. RESULTS: A significant learning curve was observed for left internal thoracic artery takedown time, y(min) = 181 - 39 x ln(x) (x = procedure number) (P <.001), and total operative time in totally endoscopic coronary artery bypass grafting, y(min) = 595 - 87 x ln(x) x = (procedure number) (P =.028). The conversion rate in totally endoscopic coronary artery bypass grafting was 2/15. Intensive care unit stay correlated significantly with total operative time (r =.427, P =.002). There was no hospital mortality. CONCLUSION: Totally endoscopic coronary artery bypass grafting can be safely implemented into a heart surgery program. Learning curves are steep for robotic left internal thoracic artery takedown and for performance of totally endoscopic coronary artery bypass grafting. Long operative times translate into prolonged intensive care unit stay in specific cases but not into increased mortality.

Vascular endothelial growth factor (VEGF) in ankylosing spondylitis--a pilot study.

INTRODUCTION: Angiogenesis is important for the pathogenesis of chronic inflammatory diseases in joints. Inflammation itself may upregulate the expression of VEGF in rheumatic diseases. Angiogenesis may become a new target for therapeutic intervention in inflammatory joint disease. AIM OF THE STUDY: To examine plasma levels of VEGF in AS patients and to test a possible correlation with serological and/or clinical parameters. PATIENTS AND METHODS: Sixteen consecutive patients with definite AS were recruited from the Gasteiner Heilstollen Hospital and compared to eight healthy probands as controls. VEGF was determined in EDTA plasma samples by using an ELISA kit. Data are given as mean values (+/- SEM). The Spearman two-sided test was used to test possible correlations. RESULTS: EDTA-plasma levels of VEGF were 75.3 +/- 19.0 pg/ml, compared to 13.8 +/- 4.7 pg/ml measured in the control group (P = 0.001). A significant correlation was found between plasma VEGF of AS patients and the BASMI score (r = 0.665, P = 0.013). Whereas VEGF was elevated in patients without treatment or NSAIDs (88.9 +/- 24.2 pg/ml), lower levels up to 43.8 pg/ml were found in patients treated with corticosteroids (34.7 +/- 4.0 pg/ml, P = 0.039). CONCLUSIONS: Disease status of AS appears to be associated with elevated VEGF plasma levels. Whether this reflects inflammation or a truly angiogenic pathomechanism requires further investigation.

Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7-ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation.

Nitric oxide (NO) generated by inducible NO synthase (iNOS) enhances vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells (VSMC) and both NO and modified low density lipoprotein (LDL) augment VEGF production in macrophages. Oxidized LDL (oxLDL) are known inhibitors of NO generation in the cells of vascular wall. As the relationship between VEGF, iNOS and oxLDL has not been well elucidated, we studied the effect of two main components of oxLDL, 7-ketocholesterol (7-Kchol) and lysophosphatidylcholine (LPC), on VEGF and NO synthesis in rat VSMC and on VEGF synthesis in human VSMC. Both LPC and 7-Kchol significantly augmented VEGF production in rat and human VSMC. Increase in VEGF generation was related to the activation of VEGF promoter by both 7-Kchol and LPC and enhancement of VEGF mRNA transcription. In rat, VSMC IL-1beta-induced NO generation and enhanced VEGF synthesis. 7-Kchol decreased rat iNOS promoter activity, iNOS expression and NO generation, but it did not impair IL-1beta-induced VEGF synthesis. LPC did not significantly influence IL-1beta-induced NO production in rat VSMC and VEGF synthesis was significantly enhanced by combined treatment with IL-1beta and LPC in comparison to the effect of either compound alone. The results indicate that VEGF and NO synthesis in VSMC can be modulated by oxLDL. Those interactions might have an effect on the plaque growth and might be of relevance for the physiology of vascular wall cells.

Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement.

OBJECTIVES: In a histopathologic study, we assessed the balance of cell proliferation and apoptosis by counting the number of apoptotic and proliferating cell nuclear antigen-positive cells in freshly harvested atherectomy specimens from 34 patients. BACKGROUND: Remodeling of human coronary arteries is an adaptive process that alters vascular lumen size. METHODS: Intravascular ultrasound was performed prior to atherectomy. Total vessel area (area within the external elastic lamina [EEL]), lumen area and plaque area were measured at the region of interest (ROI), and at a proximal and distal reference segment, utilizing the formula Delta(%)=100x(ROI-reference segment)/reference segment. Positive arterial remodeling (R+) resulting in luminal expansion was defined as DeltaEEL >10%. Absence of remodeling (0 < DeltaEEL <10%) and constrictive arterial remodeling (DeltaEEL <0) were considered as neutral remodeling (R0) and negative remodeling (R-), respectively. RESULTS: In R- lesions, apoptotic indices (APO) were significantly elevated (17.17 +/- 2.19%) compared with R+ lesions (4.89 +/- 1.7%; p = 0.0007). In a rabbit iliac percutaneous transluminal coronary angioplasty model intimal apoptosis was increased four weeks after balloon angioplasty injury (APO 8.8 +/- 0.03%) compared with contralateral untreated segments (APO 3.0 +/- 0.04%, n = 6). Lesions with an EEL/intimal area <3.0 showed significantly more intimal apoptosis than untreated lesions (p = 0.02). CONCLUSIONS: The data indicate that constrictive remodeling of atherosclerotic coronary lesions is associated with increased apoptosis of intimal cells. We speculate that increased apoptosis is due to extensive plaque healing after episodes of symptomatic or asymptomatic plaque rupture.

Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF.

OBJECTIVE: Vascular endothelial growth factor (VEGF) induces the release of nitric oxide (NO) from endothelial cells. There is also limited data suggesting that NO may enhance VEGF generation. METHODS: To further investigate this interaction, we examined the effect of exogenous and endogenous NO on the synthesis of VEGF by rat and human vascular smooth muscle cells (VSMC) by exposing cells to exogenous NO donors, or to genetic augmentation of eNOS or iNOS. RESULTS: NO-donors potentiated by 2-fold the generation of VEGF protein by rat or human VSMC. Similarly, rat or human VSMC transiently transfected with plasmid DNA encoding eNOS or iNOS, synthesized up to 3-fold more VEGF than those transfected with control plasmid DNA, an effect which was reversed after treatment with the NOS antagonist L-NAME. Rat VSMC stably transfected with pKeNOS plasmid, constitutively produced NO and released high concentrations of VEGF. In these cells, L-NAME significantly reduced NO synthesis and decreased VEGF generation. The VEGF protein produced by NOS-transfected VSMC was biologically active, as conditioned media harvested from these cells increased endothelial cell proliferation. CONCLUSION: These studies reveal that NO derived from NO-donors or generated by NOS within the cells, upregulates the synthesis of VEGF in vascular smooth muscle cells. Administration of NO donors, or augmentation of endogenous NO synthesis, may be an alternative approach in therapeutic angiogenesis.

Intravascular ultrasound predictors of major adverse cardiac events in patients with unstable angina.

BACKGROUND: Intravascular ultrasound (IVUS) predictors of native culprit lesion morphology for occurrence of major adverse cardiac events (MACE) have not been reported. Moreover, the published data on IVUS predictors of restenosis include patients with stable and unstable angina, although the development and progression of atherosclerosis related to unstable coronary syndrome is different from that of stable angina. HYPOTHESIS: This study investigated whether IVUS-derived qualitative and quantitative parameters of native (preangioplastic) plaque morphologic features can predict major adverse cardiac events in patients with unstable angina. METHODS: Clinical (age, gender, coronary risk factors), qualitative and quantitative angiographic (lesion localization, morphology, pre- and postangioplastic minimal lumen diameter, reference diameter, and percent diameter stenosis), and IVUS variables (soft/fibrocalcific plaque, calcification, presence of thrombus or plaque disruption, different types of arterial remodeling, pre- or postangioplastic minimal lumen, external elastic membrane and plaque cross-sectional area, and plaque burden of the target lesion and reference segments) were analyzed by regression analyses using the Cox model, assuming proportional hazards. RESULTS: Of 60 consecutively enrolled patients, 21 suffered from MACE, while 39 remained event-free during the followup period. Multivariate regression analyses revealed that the presence of adaptive remodeling [p = 0.0177, risk ratio (RR) = 3.108, with 95% confidence interval (CI) = 1.371-8.289] and the preangioplastic lumen cross-sectional area (p = 0.0130, RR = 0.869, with 95% CI = 0.667-0.913) are independent predictors of MACE during follow-up, as is postangioplastic angiographic minimal lumen diameter (p = 0.0330, RR = 0.715 with 95% CI = 0.678-0.812). CONCLUSIONS: Adaptive remodeling and preangioplastic lumen cross-sectional area determined by IVUS and postangioplastic minimal lumen diameter calculated by quantitative angiography are significant independent predictors of time-dependent MACE in patients with unstable angina.

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.

Short- and long-term outcomes of Wiktor stent implantation at low versus high pressures. Austrian Wiktor Stent Study Group.

A prospective, randomized, multicenter trial was conducted to evaluate whether high-pressure postdilation of the Wiktor stent provides short- and long-term benefits compared with the conventional low-pressure implantation technique. From June 1995 through May 1996, 181 patients were randomly assigned to either low-pressure (6 to 12 atm, group A, n = 94) Wiktor stent placement or to high-pressure postdilation (> or = 13 atm, group B, n = 87) after stent deployment. All patients were followed up clinically for 7 +/- 3 months, with an angiographic follow-up in 154 patients (85%). After stent implantation, neither minimal lumen diameter (MLD) nor percent diameter stenosis (%DS) differed significantly between the 2 groups (MLD, 2.8 +/- 0.5 vs 2.9 +/- 0.5 mm; %DS, 17 +/- 8% vs 16 +/- 9% for groups A and B, respectively). However, a trend toward a larger mean lumen diameter within the stent was observed in group B (3.3 +/- 0.6 vs 3.5 +/- 0.5 mm for groups A and B, respectively; difference between means 0.14 mm, 95% confidence interval -0.01 to 0.29, p = 0.08). Angiographic follow-up revealed similar MLD and %DS in both treatment groups (MLD, 2.1 +/- 0.7 vs 2.2 +/- 0.8 mm; %DS, 31 +/- 17% vs 30 +/- 24% for groups A and B, respectively, p = NS). Acute stent thrombosis occurred in 2 patients (1%) (1 patient in each group), and subacute thrombosis in 1 patient (0.6%) in group A. There was 1 death in group A, and target lesion restenosis (> or = 50% DS) was observed in 15% of patients with no differences between the groups. In conclusion, this study demonstrated favorable short- and long-term results of Wiktor stent implantation. Despite a trend toward additional initial lumen gain by high-pressure postdilation, this did not translate into a measurable improvement in long-term outcome.

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

BACKGROUND: The risk of plaque disruption and subsequent thrombosis in patients with unstable angina depends on the plaque type and size. DESIGN: Intravascular ultrasound (IVUS) was employed to illustrate the correlation between risk factors and plaque morphology in patients with unstable angina. METHODS: 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. RESULTS: 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. CONCLUSIONS: Multivariate analyses indicated that age, diabetes and hypercholesterolemia are independent predictors for plaque morphology in patients with unstable angina.

Arterial remodelling of native human coronary arteries in patients with unstable angina pectoris: a prospective intravascular ultrasound study.

OBJECTIVE: To investigate the use of intravascular ultrasound (IVUS) in detecting the presence of arterial remodelling in patients with unstable angina. DESIGN: Prospective case study. PATIENTS: 60 of 95 consecutively admitted patients with unstable angina (41 male, 19 female), mean (SD) age 61.2 (8.1) years. INTERVENTIONS: Qualitative and quantitative coronary angiography and IVUS. MAIN OUTCOME MEASURES: Adaptive or constrictive remodelling (AR, CR) was considered present when the cross sectional area of the external elastic membrane at the lesion site was larger than the proximal cross sectional area or smaller than the distal cross sectional area, respectively. RESULTS: 22 of the 60 patients (37%) showed AR and 14 (23%) showed CR. No remodelling was seen in 24 patients (group NR). The plaque contained more thrombus and plaque rupture in group AR than in groups CR and NR (thrombus: 91% v 50% and 67%, respectively, p = 0.023; rupture: 73% v 29% and 42%, p = 0.020). AR was associated with a larger plaque cross sectional area (12.6 (SD 4.6) mm2 v 10.8 (6.3) and 9.2 (3.7) mm2, p = 0.001) and larger external elastic membrane cross sectional area (16.5 (5.8) mm2 v 13.2 (5.2) and 14.4 (3.6) mm2, p = 0.01 in group AR v groups CR and NR, respectively), while the plaque burden was larger in groups AR (74.9 (9.1)%) and CR (72.4 (16.6)%) than in group NR (66.2 (18.1)%, p = 0.005). CONCLUSIONS: IVUS is capable of detecting adaptive and constrictive remodelling of target lesions and its relation to plaque morphology in unstable angina.

Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.

Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis.

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N=16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700+/-500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1+/-34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8%+/-14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1+/-28.5 mg/dL (-54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. Lp(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1,420+/-380 mg; without elevated Lp(a), 235+/-190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.

Impairment of endothelium-independent vasodilation in patients with hypercalcemia.

OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT. METHODS: Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz). RESULTS: NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017). CONCLUSIONS: Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.