Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of ...endothelial function and other vascular markers in apparently healthy men.
The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24).
In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.
Although flow-mediated dilatation (FMD) is widely used, the ideal vascular parameter for the measurement of cardiovascular risk is not clear. Recently, it has been proposed that shear stress and ...blood velocity during hyperemia (VRH) may provide stronger correlations with cardiovascular risk factors than FMD. The aim of this study was to evaluate the relations of VRH and shear stress during reactive hyperemia (SSRH) to FMD and the association of these measures to cardiovascular risk factors in 1,477 men without cardiovascular disease. SSRH and VRH showed weak correlations with FMD in bivariate analysis (r = 0.239, p <0.001, and r = 0.108, p <0.001, respectively). The only cardiovascular risk factor independently associated with FMD was systolic blood pressure (β = −0.073, p <0.01). In contrast, as the dependent variable, SSRH (R2 for model = 0.107) was independently associated with age, systolic blood pressure, low-density lipoprotein cholesterol, and body mass index. As the dependent variable, VRH was associated with the same risk factors with a slightly weaker R2 value of 0.095. In conclusion, SSRH and simply calculated VRH have stronger associations with cardiovascular risk factors than FMD. This may reflect greater sensitivity of these measures to detect early abnormalities associated with risk factors in a relatively young and healthy population.
We assessed the safety and effectiveness of the sirolimus-eluting stent (SES) in treating single de novo long lesions in small native coronary arteries compared to an identical bare metal stent ...(BMS).
The SES was previously demonstrated to reduce restenosis significantly. However, patients with long lesions in small vessels have not been well studied and may define a group at very high risk.
The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients With Long De Novo Lesions in Small Native Coronary Arteries (C-SIRIUS) was a multicenter, randomized, double-blind trial comparing SES versus identical BMS. The primary end point was in-stent minimal lumen diameter (MLD) at eight months. Secondary end points included angiographic restenosis at 8 months, target lesion revascularization (TLR), and major adverse cardiac events (MACE) at 270 days.
A total of 100 patients were enrolled at eight Canadian sites. The in-stent MLD at eight months was 2.46 ± 0.37 mm in the SES compared with 1.49 ± 0.75 mm in the BMS (a 65% increase, p < 0.001). Angiographic restenosis occurred in 1 of 44 SES patients (2.3%, with no in-stent restenosis) and in 23 of 44 BMS patients (52.3%, p < 0.001). At 270 days, there were two clinically driven TLRs in the SES (4%) and nine in the BMS (18%, p = 0.05). The Kaplan-Meier estimate of freedom from MACE at 270 days was 96.0% for SES patients and 81.7% for BMS patients (p = 0.029).
Patients with long lesions in small vessels are at very high risk of restenosis. In these patients, the SES dramatically reduces the risk of restenosis at eight months, translating into an excellent clinical outcome at nine months.
Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce ...experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis.
This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level <125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was approximately 200 mm3, and the least squares mean change at end of treatment was 0.7 mm3 for placebo and 7.7, 4.1, and 4.8 mm3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted P=0.17 unadjusted P=0.057, 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (P=NS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups).
Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol.
Objective:
Numerous indexes of adiposity have been proposed and are currently in use in clinical practice and research. However, the correlation of these indexes with measures of vascular health ...remain poorly defined. This study investigated which measure of adiposity is most strongly associated with endothelial function.
Design and Methods:
Data from the Firefighters And Their Endothelium (FATE) study was used. The relationships between three measures of vascular function: flow‐mediated dilation (FMD), hyperemic velocity time integral (VTI), and hyperemic shear stress (HSS), and five measures of adiposity: BMI, waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR), and body adiposity index (BAI) were tested. Univariate comparisons were made, and subsequently models adjusted for traditional risk factors were constructed.
Results:
A total of 1,462 male firefighters (mean age 49 ± 9) without cardiovascular disease comprised the study population. No measure of adiposity correlated with FMD; all five measures of adiposity were negatively correlated with VTI and HSS (P values <0.0001), with WHtR most strongly correlated with VTI, and WC most strongly correlated with HSS (both P < 0.05). In models including all five measures of obesity simultaneously, BMI, WC, and WHtR were all predictive of HSS (all P values <0.05), and BMI and WHR were both predictive of VTI (P values <0.05).
Conclusions:
Anthropometric measures of adiposity may help refine estimations of atherosclerotic burden. BMI was most consistently associated with endothelial dysfunction, but measures of adiposity that reflect distribution of mass were additive.
This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors.
Most cardiovascular ...clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease.
All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals.
The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked >or=150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 +/- 0.13 kg/m(2) to 29.3 +/- 0.23 kg/m(2) (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 +/- 0.49 mm Hg to 123 +/- 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 +/- 0.83 mg/dl to 72 +/- 0.88 mg/dl.
Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).
OBJECTIVES
The goal of this study was to determine whether postprandial hyperglycemia, induced by oral glucose loading, attenuates endothelial function in healthy subjects without diabetes and ...whether coadministration of vitamins C and E could prevent these postprandial changes.
BACKGROUND
Epidemiologic evidence suggests that postprandial hyperglycemia, below diabetic levels, is a risk factor for cardiovascular disease. Postprandial hyperglycemia may promote atherosclerosis through endothelial dysfunction and oxidative stress.
METHODS
We evaluated the acute effects of oral glucose loading (75 g), alone and with vitamins C (2 g) and E (800 IU), on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, in a randomized, double-blind, placebo-controlled, crossover study of 10 healthy volunteers. Changes in the levels of markers of oxidative stress (plasma malondialdehyde and erythrocyte glutathione, glutathione peroxidase and superoxide dismutase) were also assessed.
RESULTS
Increases in plasma glucose and insulin after glucose loading were unaffected by vitamin coadministration. With glucose loading alone, FMD fell from 6.5 ± 2.2 at baseline to 5.4 ± 1.7, 3.7 ± 2.1∗, 4.1 ± 3.5∗ and 5.7 ± 1.9% at 1, 2, 3 and 4 h (∗p < 0.05 vs. 0 h). In contrast, FMD did not change significantly after glucose plus vitamins (6.4 ± 1.3, 7.6 ± 1.8, 7.9 ± 2.7, 6.9 ± 2.3, 6.9 ± 1.9% at 0, 1, 2, 3 and 4 h). By two-way repeated measures analysis of variance we found a significant interaction between vitamin treatment and time (p = 0.0003), indicating that vitamins prevented the glucose-induced attenuation of FMD. Oxidative stress markers did not significantly change with glucose loading alone or with vitamins.
CONCLUSIONS
Oral glucose loading causes an acute, transient decrease of FMD in healthy subjects without diabetes, which is prevented by vitamins C and E.
Abstract Background Existing criteria recommended by ACC/ESC for identifying patients with ST elevation myocardial infarction (STEMI) from the 12-lead ECG perform with high specificity ( SP ), but ...low sensitivity ( SE ). In our previous studies, we found that the SE of ischemia detection can be markedly improved without any loss of SP by calculating, from the 12-lead ECG, ST deviation in 3 “optimal” vessel-specific leads (VSLs). Our original VSLs, based on ΔST body-surface potential maps (BSPMs), have been modified by using the more appropriate J-point BSPMs at peak ischemia (without subtraction of pre-occlusion distributions). The aim of the present study was to compare the performance of these new VSLs with that achieved by the STEMI criteria used in current practice. Methods Two independent datasets of 12-lead ECGs were used: the STAFF III dataset acquired during ischemic episodes caused by balloon inflation in LAD ( n = 35), RCA ( n = 47), and LCx ( n = 17) coronary arteries, and the Glasgow dataset comprising admission 12-lead ECGs of 116 patients who were hospitalized for chest pain and underwent contrast-enhanced cardiac MRI that confirmed AMI in 58 patients (50%). Results We found that, in the STAFF III dataset, the detection of ischemic state by the STEMI criteria attained SE/SP of 60/97%, whereas SE/SP values of VSLs were 72/98%. In the Glasgow dataset, STEMI criteria yielded SE/SP of 43/98%, whereas the VSLs improved SE/SP to 60/98%. The most significant increase in diagnostic performance appeared in patients with LCx coronary artery occlusion: in STAFF III data ( n = 17) SE achieved by STEMI criteria was improved by the VSLs from 35% to 71%; in Glasgow data ( n = 12) SE of 31% achieved by STEMI criteria was improved by the VSLs to 69%. Conclusion In our study population, existing ACC/ESC STEMI criteria complemented by the new VSLs yielded much improved sensitivity of ischemia detection without any detrimental effect on specificity. This finding needs to be corroborated on a larger chest-pain patient population with typical prevalence of acute ischemia presented to the emergency rooms.
Abstract Background The antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently ...modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis. Methods and results This placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd started before percutaneous coronary intervention (PCI) and administered for 12 months after PCI on atherosclerosis progression as assessed by coronary intravascular ultrasound (IVUS). Among patients with IVUS examinations considered technically adequate both at baseline and follow-up upon central laboratory assessments ( n = 232), plaque volume was not significantly modified with placebo (least squares mean change: −0.4 mm3 , P = 0.85 versus baseline), but was significantly reduced by −4.0 mm3 at end of treatment in the AGI-1067 group ( P = 0.001 versus baseline, P = 0.12 versus placebo). LDL-cholesterol varied by −9% and +4% in the placebo and AGI-1067 groups, respectively ( P < 0.05 between groups), and HDL-cholesterol was reduced by 1% with placebo and 14% with AGI-1067 ( P < 0.05 between groups). Plasma myeloperoxidase was reduced by 6% with AGI-1067 ( P < 0.05) but hs-CRP was not significantly different between groups. Conclusions Atherosclerosis regression (−4.0 mm3 ) was observed in patients treated with AGI-1067, although this was not significantly different from placebo. The anti-inflammatory effect of AGI-1067 is supported by reduced levels of myeloperoxidase.
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