Risk prediction models for discrete ordinal outcomes: Calibration and the impact of the proportional odds assumption.

Calibration is a vital aspect of the performance of risk prediction models, but research in the context of ordinal outcomes is scarce. This study compared calibration measures for risk models predicting a discrete ordinal outcome, and investigated the impact of the proportional odds assumption on calibration and overfitting. We studied the multinomial, cumulative, adjacent category, continuation ratio, and stereotype logit/logistic models. To assess calibration, we investigated calibration intercepts and slopes, calibration plots, and the estimated calibration index. Using large sample simulations, we studied the performance of models for risk estimation under various conditions, assuming that the true model has either a multinomial logistic form or a cumulative logit proportional odds form. Small sample simulations were used to compare the tendency for overfitting between models. As a case study, we developed models to diagnose the degree of coronary artery disease (five categories) in symptomatic patients. When the true model was multinomial logistic, proportional odds models often yielded poor risk estimates, with calibration slopes deviating considerably from unity even on large model development datasets. The stereotype logistic model improved the calibration slope, but still provided biased risk estimates for individual patients. When the true model had a cumulative logit proportional odds form, multinomial logistic regression provided biased risk estimates, although these biases were modest. Nonproportional odds models require more parameters to be estimated from the data, and hence suffered more from overfitting. Despite larger sample size requirements, we generally recommend multinomial logistic regression for risk prediction modeling of discrete ordinal outcomes.

[Secondary prevention with antiplatelet therapy in cardiac rehabilitation]. / Sekundärpräventive Antiplättchentherapie in der kardiologischen Rehabilitation.

The long-term increased cardiovascular risk of patients with an acute coronary syndrome (ACS) is a challenging and common clinical problem. Recent evidence demonstrated an ischemic benefit for a prolonged dual antiplatelet therapy beyond the initial 12 months at the cost of an increased bleeding risk. Individual, careful and repeated risk-benefit analyses are essential for an optimized patient management in which cardiovascular rehabilitation providers may play a central role.

Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.

AIMS Pre-treatment with clopidogrel results in a reduction of ischaemic events in non-ST-elevation acute coronary syndromes. Data on upstream clopidogrel in the setting of primary percutaneous coronary intervention (PCI) are limited. The aim of this study was to investigate whether clopidogrel loading before arrival at the PCI centre may result in an improved outcome of primary PCI for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In a multicentre registry of acute PCI, 5955 patients undergoing primary PCI in Austria between January 2005 and December 2009 were prospectively enrolled. The patients consisted of two groups, a clopidogrel pre-treatment group (n = 1635 patients) receiving clopidogrel before arrival at the PCI centre and a peri-interventional clopidogrel group (n = 4320 patients) receiving clopidogrel at a later stage. Multiple logistic regression analysis including major confounding factors stratified by the participating centres was applied to investigate the effect of pre-treatment with clopidogrel on the in-hospital mortality. Additionally, two subgroups, with or without the use of GP IIb/IIIa antagonist therapy in the catheterization laboratory, were analysed. On univariate analysis, clopidogrel pre-treatment was associated with a reduced in-hospital mortality (3.4 vs. 6.1%, P< 0.01) after primary PCI. On multivariate analysis, clopidogrel pre-treatment remained an independent predictor of in-hospital mortality [odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.35-0.99; P =0.048], especially in patients receiving additional GP IIb/IIIa antagonist therapy in the catheterization laboratory (OR = 0.40, 95% CI 0.19-0.83; P =0.01). CONCLUSION Clopidogrel pre-treatment before arrival at the PCI centre is associated with reduced mortality in a real world setting of primary PCI. These results strongly support the recommendation of clopidogrel treatment 'as soon as possible' in patients with STEMI undergoing pimary PCI.

Improved in-hospital outcome for radial access in a large contemporary cohort of primary percutaneous coronary intervention.

BACKGROUND: Randomised controlled trials have shown diverse results for radial access in patients undergoing primary percutaneous coronary intervention (PPCI). Moreover, it is questionable whether radial access improves outcome in patients with cardiogenic shock undergoing PPCI. We aimed to investigate the outcome according to access site in patients with or without cardiogenic shock, in daily clinical practice. METHODS: For the present analysis we included 9,980 patients undergoing PPCI between 2012 and 2018, registered in the multi-centre, nationwide registry on PCI for myocardial infarction (MI). In-hospital mortality, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE) until discharge were compared between 4,498 patients with radial (45%) and 5,482 patients with femoral (55%) access. RESULTS: Radial compared to femoral access was associated with lower in-hospital mortality (3.5% vs. 7.7%; P<0.01). Multivariable logistic regression analysis confirmed reduced in-hospital mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.43 to 0.75]. Furthermore, MACE (OR 0.60, 95% CI: 0.47 to 0.78) as well as NACE (OR 0.59, 95% CI: 0.46 to 0.75) occurred less frequently in patients with radial access. Interaction analysis with cardiogenic shock showed an effect modification, resulting in lower mortality in PCI via radial access in patients without, but no difference in those with cardiogenic shock (OR 1.78, 95% CI: 1.07 to 2.96). CONCLUSIONS: Radial access for patients with acute MI undergoing PPCI is associated with improved survival in a large contemporary cohort of daily practice. However, this beneficial effect is restricted to hemodynamically stable patients.

[STEMI guidelines 2008--Do they influence today's myocardial infarction treatment strategies in rural areas?]. / STEMI-Guidelines 2008--Konsequenzen für die heutige Infarktversorgung im ländlichen Raum?

2008 new guidelines for the management of patients with ST-elevation myocardial infarction were published by the European Society of Cardiology. For daily clinical practice, changes in recommendations concerning the preferred revascularization therapy according to different time delays are of great interest. This review focuses on possible implications of these new guidelines on the choice of reperfusion strategies in rural areas.

Changes and innovations of the 2017 ESC guidelines on dual antiplatelet therapy in coronary artery disease-a review.

Duration and compostion of dual antiplatelet therapy has been increasingly changed within the past few years as also indicated in the firmer ESC guidelines. The current manuscript summarizes the most important changes in dual antiplatelet therapy as shown by a recent ESC position paper and offers quick insight into these new developments.

Cohort profile: the Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort.

PURPOSE: The Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort is aimed to gain a better understanding of cardiovascular risk factors and their relation to the diagnosis and severity of coronary artery disease, as well as to the long-term prognosis in consecutive (including revascularised) patients referred for elective coronary angiography. PARTICIPANTS: The included patients visited the University Clinic of Cardiology at Innsbruck (Austria), which fulfils a secondary and tertiary hospital function. Inclusion took place in the period between February 2004 and April 2008 and resulted in a total of 8296 patients aged 18-91 years; 65% of them were men. FINDINGS TO DATE: There was one follow-up round on vital status through record linkage for 84% of the cohort (those with residence in Tyrol), resulting in a follow-up duration of over 5.5 to nearly 10.0 years among survivors. The data contain basic patient characteristics, cardiovascular risk factors, laboratory measurements, medications, detailed information on the extent and severity of coronary artery disease, revascularisation history, treatment strategy and mortality specifics. A few studies have already been published. FUTURE PLANS: Various diagnostic and prognostic studies are planned, also concerning complications, competing risks and cost-effectiveness. Collaboration with other research groups is welcomed.

External validation and extension of a diagnostic model for obstructive coronary artery disease: a cross-sectional predictive evaluation in 4888 patients of the Austrian Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort.

OBJECTIVE: To externally validate and extend a recently proposed prediction model to diagnose obstructive coronary artery disease (CAD), with the ultimate aim to better select patients for coronary angiography. DESIGN: Analysis of individual baseline data of a prospective cardiology cohort. SETTING: Single-centre secondary and tertiary cardiology clinic. PARTICIPANTS: 4888 patients with suspected CAD, without known previous CAD or other heart diseases, who underwent an elective coronary angiography between 2004 and 2008 as part of the prospective Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. Relevant data were recorded as in routine clinical practice. MAIN OUTCOME MEASURES: The probability of obstructive CAD, defined as a stenosis of minimally 50% diameter in at least one of the main coronary arteries, estimated with the predictors age, sex, type of chest pain, diabetes status, hypertension, dyslipidaemia, smoking status and laboratory data. Missing predictor data were multiply imputed. Performance of the suggested models was evaluated according to discrimination (area under the receiver operating characteristic curve, depicted by the c statistic) and calibration. Logistic regression modelling was applied for model updating. RESULTS: Among the 4888 participants (38% women and 62% men), 2127 (44%) had an obstructive CAD. The previously proposed model had a c statistic of 0.69 (95% CI 0.67 to 0.70), which was lower than the expected c statistic while correcting for case mix (c=0.80). Regarding calibration, there was overprediction of risk for high-risk patients. All logistic regression coefficients were smaller than expected, especially for the predictor 'chest pain'. Extension of the model with high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and C reactive protein led to better discrimination (c=0.72, 95% CI 0.71 to 0.74, p<0.001 for improvement). CONCLUSIONS: The proposed prediction model has a moderate performance to diagnose obstructive CAD in an unselected patient group with suspected CAD referred for elective CA. A small, but significant improvement was attained by including easily available and measurable cardiovascular risk factors.

Countervailing effects of rapamycin (sirolimus) on nuclear factor-kappa B activities in neointimal and medial smooth muscle cells.

OBJECTIVE: Local application of rapamycin (sirolimus) by drug-eluting stents prevents lumen obliteration after angioplasty by inhibition of neointimal hyperplasia. The effects of rapamycin on neointimal smooth muscle cells (niSMC) which are responsible for the occurrence of restenosis have not been investigated so far. METHODS AND RESULTS: Rat niSMC and medial SMC (mSMC) were obtained from balloon catheter-injured arteries. The niSMC exhibited higher basal NF-kappaB activity and TNF-alpha mRNA levels. Nuclear protein binding to NF-kappaB-DNA was attenuated in niSMC by incubation with rapamycin (0.1 and 1 microg/ml) for 24 and 48 h. In contrast in mSMC, 0.1 microg/ml rapamycin had no effect and at 1 microg/ml even increased nuclear protein binding to NF-kappaB-DNA. After 12 h incubation, rapamycin (0.001-10 microg/ml) induced IkappaB-alpha protein in niSMC, whereas in mSMC it stimulated IkappaB-alpha at much lower levels. Prolonged rapamycin treatment (1 microg/ml for 72 h) had no effect on TNF-alpha mRNA level and NF-kappaB activity in niSMC, whereas it led to their increase in mSMC. Vascular endothelial growth factor (VEGF) secretion was higher in mSMC than in niSMC; rapamycin decreased VEGF levels in both cell types. Ultrastructural analysis suggested that rapamycin caused early signs of degeneration in niSMC, but enhanced protein synthesis in mSMC. CONCLUSIONS: This study shows that rapamycin influences the inflammatory phenotypes of SMC in opposite directions: it reduces the high basal NF-kappaB activity in niSMC and enhances NF-kappaB activity and TNF-alpha expression in mSMC. In addition, rapamycin inhibits VEGF production regardless of the phenotype of SMC. These findings shed light on molecular mechanisms and structural changes underlying therapeutic applications of rapamycin in prevention of restenosis, inhibition of chronic transplant arteriosclerosis and reduction of secondary malignoma formation due to immunosuppression.

Short-term improvement in submaximal exercise capacity by optimized therapy with ACE inhibitors and beta blockers in heart failure patients is associated with restoration of peripheral endothelial function.

BACKGROUND: Improved exercise capacity in chronic heart failure (CHF) has been attributed to restoration of endothelial function. ACE inhibitors as well as beta blockers have previously been shown to enhance endothelial function and exercise capacity. The aim of this study was to determine whether short-term improvement in submaximal exercise capacity induced by optimized therapy with ACE inhibitors in combination with beta blockers is associated with restoration of endothelial function in CHF patients. METHODS: Thirty-three patients with CHF were evaluated: six-minute walk test, NYHA class, brain natriuretic peptide (BNP), big Endothelin-1 (bigET-1) and flow-mediated vasodilation (FMD) of the brachial artery were assessed at baseline and after a 3-month period of optimized neurohormonal therapy. Two groups were formed retrospectively based on the changes in submaximal exercise capacity (responders and non-responders). RESULTS: Optimization of neurohormonal therapy was comparable between groups. Responders (n=17) revealed a significant increase in walking distance (304+/-109 to 441+/-75 m; p<0.01), which was paralleled by a decrease in NYHA class (2.7+/-0.6 to 2.0+/-0.4; p<0.01), BNP (484+/-454 to 243+/-197 pg/ml; p<0.01), and bigET-1 (2.0+/-0.9 vs. 1.5+/-0.6 fmol/ml; p=0.04). By contrast, the latter variables did not change in non-responders. Improvement in functional capacity in responders was associated with an increase in FMD (8.2+/-3.9% to 11.0+/-5.6%; p<0.05). Increments in FMD were directly correlated with increases in walking distance (r=0.34; p<0.05). CONCLUSION: Short-term improvement of submaximal exercise capacity in CHF patients following optimized therapy with ACE inhibitors and beta blockers is associated with restoration of endothelial function in conduit arteries.

Transient impairment of flow-mediated vasodilation in patients with metabolic syndrome at moderate altitude (1,700 m).

BACKGROUND: The influence of moderate altitude on the cardiovascular system in patients with metabolic syndrome has not been investigated sufficiently, yet. The aim of this study was to assess the effect of acute and mid-term exposure to moderate altitude (1,700 m) on endothelial function in patients with metabolic syndrome. METHODS: Flow-mediated (FMD) and nitroglycerin-mediated vasodilation (NMD) were assessed in 18 patients with coronary risk factors on 5 occasions: (1) at location A (576 m), (2) on the first day at moderate altitude (location B, 1,700 m), (3) after 3 weeks at moderate altitude, (4) and (5) again at location A (6 and 16 weeks after the stay at moderate altitude, respectively). In addition, markers of lipid metabolism, serum erythropoietin and endothelin were measured. RESULTS: FMD on the first day at moderate altitude was similar compared to baseline FMD at location A (7.0 +/- 3.3 vs. 7.4 +/- 4.6%; NS). A 3-week stay at moderate altitude was associated with a significant reduction in FMD (7.4 +/- 4.6 vs. 3.8 +/- 2.5%; p < 0.05) despite a decrease in baseline diameter (4.5 +/- 0.3 vs. 4.3 +/- 0.4 mm; p < 0.05). Six weeks after returning to location A, FMD was still reduced compared to baseline (4.3 +/- 2.8%; p < 0.05) and after further 16 weeks, FMD returned to baseline values (5.5 +/- 3.5%). However, metabolic parameters improved significantly. In contrast, NMD and endothelin levels remained unchanged. CONCLUSION: In patients with metabolic syndrome, a sojourn of 3 weeks at moderate altitude leads to a prolonged, but reversible impairment of FMD. The discrepancy to improvement of other cardiovascular and metabolic parameters requires further investigation.

Aortic valve calcification as quantified with multislice computed tomography predicts short-term clinical outcome in patients with asymptomatic aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Aortic valve calcification may be an independent risk factor for adverse clinical outcome. The study aim was to assess the predictive value of possible risk factors, including the severity of aortic valve calcification as quantified with 16-multislice computed tomography (MSCT) for adverse short-term clinical outcome in patients with asymptomatic, degenerative aortic stenosis (AS). METHODS: Possible risk factors for adverse short-term clinical outcome were prospectively tested in 34 consecutive patients with asymptomatic AS as follows: (i) aortic valve calcium (AVC) score as quantified with MSCT; (ii) echocardiographic parameters--aortic valve area (AVA) calculated with continuity equation, mean and maximal transvalvular pressure gradients, end-diastolic septal wall diameter; and (iii) laboratory tests (brain natriuretic peptide (BNP), C-reactive protein (CRP)). RESULTS: Within 18-24 months of follow up, 11 of 34 patients developed a major adverse clinical outcome. Ten patients suffered from onset of symptoms accompanied by hemodynamic progression, and one patient died from sudden cardiac death. Six of these 10 patients underwent aortic valve replacement, one patient declined surgery, and three patients were not accepted for surgery (one of these died suddenly shortly afterwards). The aortic valve calcium score was the strongest predictor of a major adverse clinical event (p < 0.001) among all parameters assessed (1,928 +/- 789 versus 5,111 +/- 2,409 Agatston units). The plasma level of BNP (p = 0.003), mean transvalvular pressure gradient (p = 0.002) and AVA (p = 0.003) were also risk factors for adverse clinical outcome. CONCLUSION: The AVC score as quantified with MSCT predicted adverse short-term clinical outcome in patients with asymptomatic AS. In patients with severe aortic valve calcification, close follow up examinations are mandatory, and early elective surgery may be considered even in the absence of symptoms. MSCT provides a comprehensive non-invasive imaging approach for risk stratification in patients with asymptomatic AS.

Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction.

The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT.

Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis.

OBJECTIVES: The purpose of this study was to determine the relationship among coronary atherosclerosis and functional, morphologic, and mechanical parameters assessed noninvasively within the brachial artery (BA). BACKGROUND: Flow-mediated vasodilation (FMD) of the BA, intima-media thickness (IMT) of the carotid artery, and distensibility of the aorta have been correlated with the presence of coronary artery disease (CAD). METHODS: The BA was examined with high-resolution ultrasound (13 MHz) in 117 male patients, in whom coronary angiography was performed. Coronary artery disease (> or =30% diameter stenosis in > or =1 major branch) was found in 84 patients, and 33 patients had smooth coronary arteries (non-CAD). Wall cross-sectional area (WCSA) was calculated from resting diameter and IMT. RESULTS: The BA-WCSA (5.3 +/- 1.5 mm(2) vs. 4.4 +/- 1.4 mm(2), p = 0.002) and IMT (0.37 +/- 0.07 mm vs. 0.31 +/- 0.07 mm, p < 0.001) were significantly greater in patients with CAD compared with non-CAD patients. Flow-mediated vasodilation and distensibility were similar among groups. Using logistic regression analyses adjusting for age, positive family history, hypertension, hypercholesterolemia, smoking, FMD, and distensibility, only WCSA (p < 0.01) and IMT (p < 0.001) correlated independently with the presence of CAD. CONCLUSIONS: Morphologic but not functional and mechanical parameters of the BA are associated with the presence of CAD. Among BA sonographic parameters, IMT and WCSA seem to be the most accurate ones for the estimation of coronary atherosclerotic risk.

Chronic heart failure is associated with vascular remodeling of the brachial artery.

AIMS: Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in peripheral conduit arteries and with systemic overexpression of ET-1 in patients suffering from CHF. METHODS AND RESULTS: 57 consecutive patients referred to the Innsbruck Heart Failure and Transplantation Program (EF=23+/-7%) and 16 matched controls (EF=60+/-5%) were studied. Flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), wall thickness (WT), and incremental elastic modulus (Einc) were assessed by high-resolution ultrasound of the brachial artery. FMD (P=0.004) and NMD (P=0.02) were significantly higher in controls as compared to moderate and severe CHF patients. In contrast, brachial artery-wall thickness (BA-WT) was increased in severe CHF patients (P=0.038). BA-WT was significantly correlated with both FMD (r=-0.28; P=0.049) and NMD (r=-0.38; P=0.003), and with the Einc (r=0.45, P=0.001). Lumen diameter was not different among groups. In patients with BA-WT>0.31 mm, bigET-1 was higher compared to BA-WT<0.31 mm (P<0.05). CONCLUSION: CHF is associated with remodeling of the brachial artery, which is characterized by morphological, mechanical and functional changes of the vessel wall. Endothelin-1 may play a role in the vascular remodeling process.

HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells.

OBJECTIVE: Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. METHODS AND RESULTS: Simvastatin, atorvastatin, and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia-inducible factor-1alpha. Downstream effects of statins included inhibition of plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA levels in endothelial cells. CONCLUSIONS: HMG-CoA reductase inhibitors downregulate the activation of transcription factors NF-kappaB, AP-1, and hypoxia-inducible factor-1alpha. These findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.

[The role of inflammation in the pathophysiology of acute coronary syndromes]. / Die Rolle der Inflammation in der Pathophysiologie akuter Koronarsyndrome.

All stages of atherosclerotic plaques are characterized by an inflammatory component, in which T lymphocytes and macrophages orchestrate lesion progression and destabilization by releasing cytokines (e.g., interferon-gamma, tumor necrosis factor-alpha, tissue factor). At the extreme end of this process plaque rupture occurs, which may manifest clinically as an acute coronary syndrome. Hence, measuring this atherosclerosis-inherent inflammation may help predicting cardiovascular events. Accordingly, different soluble inflammatory markers were studied for their predictive value in acute coronary syndromes. Special attention was paid to high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L). The latter seems not only to be a marker of inflammation and platelet activation, but is suggested to directly destabilize atherosclerotic plaques by stimulating pro-inflammatory T lymphocytes. Therefore, reduction of soluble inflammatory markers is an attractive target for future therapeutic strategies. Statins and glycoprotein IIb/IIIa antagonists, well-established treatments in acute coronary syndromes, were demonstrated to decrease hs-CRP and sCD40L. Whether this reduction translates into a better prognosis has to be investigated in further studies.

Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease.

Intima-media thickness of the carotid and femoral arteries has been associated with coronary atherosclerosis and its clinical sequelae. The brachial artery (BA) is widely used for the assessment of flow-mediated vasodilation. The aim of this study was to examine whether BA wall thickness (WT) is associated with coronary artery disease (CAD) and risk factors. High-resolution ultrasound (13 MHz) examination of the BA was performed in 179 patients undergoing coronary angiography for the evaluation of chest pain. CAD (> or =30% diameter stenosis in > or =1 major branch) was found in 132 patients, whereas 47 patients had smooth coronary arteries. WT of the posterior BA wall (0.4 +/- 0.05 vs 0.35 +/- 0.06 mm, p <0.001) and wall index (WI) (WT/vessel diameter x 100; 16.1 +/- 0.0 vs 13.8 +/- 0.8, p <0.001) were greater in patients with than without CAD. On univariate analysis, WT and WI correlated with age, presence of CAD, systemic hypertension, maximum coronary diameter stenosis, and baseline diameter. On logistic regression analyses adjusting for age, cholesterol levels, systemic hypertension, smoking, and positive family history, WT (p <0.01) and WI (p = 0.02) remained significantly correlated with the presence of CAD. Thus, BA-WT is independently correlated with the presence of CAD. WT may provide a novel noninvasive marker of atherosclerosis that can be assessed together with flow-mediated vasodilation to yield functional and morphologic information in the same vessel.

Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy.

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy. METHODS: Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4 and 10 months in 18 consecutively recruited patients with coronary artery disease (CAD), in whom statin therapy was newly established. RESULTS: The decrease of total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/- 31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/- 2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/- 5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs. 0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained improvement of endothelial function up to 10 months. These data support the utility of FMD for the assessment of vascular function in response to lipid-lowering therapy or other therapeutic interventions in long-term studies.