Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease.

OBJECTIVES: The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured noninvasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local coronary artery disease (CAD), in a given patient, is related to the degree of local abnormal coronary endothelial function. BACKGROUND: Abnormal endothelial function mediates the initiation and progression of atherosclerosis and predicts cardiovascular events. However, direct measures of coronary endothelial function have required invasive assessment. METHODS: The MRI was performed in 20 healthy adults and 17 patients with CAD. Cross-sectional coronary area and blood flow were quantified before and during isometric handgrip exercise, an endothelial-dependent stressor. In 10 severe, single-vessel CAD patients, paired endothelial function was measured in the artery with severe stenosis and the contralateral artery with minimal disease. RESULTS: In healthy adults, coronary arteries dilated and flow increased with stress. In CAD patients, coronary artery area and blood flow decreased with stress (both p </= 0.02). In the paired study, coronary artery area and blood flow failed to increase during exercise in the mildly diseased vessel, but both area (p = 0.01) and blood flow (p = 0.02) decreased significantly in the severely diseased, contralateral artery. CONCLUSIONS: Endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified noninvasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.

Change in physical activity after smoking cessation: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. DESIGN, SETTING AND PARTICIPANTS: A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. MEASUREMENTS: Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. FINDINGS: We found significant interactions by race/sex (P = 0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI) = -0.20 to -0.07, P < 0.001 for white women]. An increase in physical activity was associated with years since smoking cessation in white men (coefficient 0.06; 95% CI = 0 to 0.13, P = 0.05). The physical activity trajectory for people who quit diverged progressively towards higher physical activity from the expected trajectory had smoking continued. For example, physical activity was 34% higher (95% CI = 18 to 52%; P < 0.001) for white women 10 years after stopping compared with continuing smoking for those 10 years (P = 0.21 for race/sex differences). CONCLUSIONS: Smokers who quit have progressively higher levels of physical activity in the years after quitting compared with continuing smokers.

SPECT myocardial perfusion imaging: long-term prognostic value in diabetic patients with and without coronary artery disease.

AIM: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. PATIENTS, METHODS: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. RESULTS: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65 +/- 10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p < 0.0001), followed by history of CAD (Hazard Ratio (HR) = 15.9; p = 0.0001), diabetic retinopathy (HR = 10.0; p = 0.001) and inability to exercise (HR = 7.7; p = 0.02). Patients with normal MPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. CONCLUSION: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a >5-fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients.

Selective coronary artery plaque visualization and differentiation by contrast-enhanced inversion prepared MRI.

AIMS: We sought to evaluate the utility of contrast-enhanced coronary magnetic resonance imaging (CE-MRI) for selective visualization and non-invasive differentiation of atherosclerotic coronary plaque in humans. METHODS AND RESULTS: Nine patients with coronary artery disease (CAD) as confirmed by X-ray angiography and multidetector computed tomography (MDCT) were studied by T1-weighted black blood inversion recovery coronary MRI before (N-IR) and after administration of Gd-DTPA (CE-IR). Plaques were categorized as calcified, non-calcified, and mixed based on their Hounsfield number derived from MDCT. With MDCT, a total of 29 plaques were identified, including calcified (n=6), non-calcified (n=6), and mixed calcified/non-calcified (n=17). On N-IR MRI, 26 plaques (90%) were dark, whereas three plaques (two non-calcified and one mixed) appeared bright. On CE-MRI, 13/29 (45%) plaques, 11 of which were mixed, one non-calcified, and one calcified showed contrast uptake. All others remained dark. CONCLUSION: In this preliminary study, we demonstrate the potential utility of CE-IR MRI for selective plaque visualization and differentiation of plaque types. The observed contrast uptake may be associated with endothelial dysfunction, neovascularization, inflammation, and/or fibrosis.

Initial experiences with in vivo right coronary artery human MR vessel wall imaging at 3 tesla.

Due to their relatively small size and central location within the thorax, improvement in signal-to-noise (SNR) is of paramount importance for in vivo coronary vessel wall imaging. Thus, with higher field strengths, coronary vessel wall imaging is likely to benefit from the expected "near linear" proportional gain in SNR. In this study, we demonstrate the feasibility of in vivo human high field (3 T) coronary vessel wall imaging using a free-breathing black blood fast gradient echo technique with respiratory navigator gating and real-time motion correction. With the broader availability of more SNR efficient fast spin echo and spiral techniques, further improvements can be expected.

High prevalence of major cardiovascular risk factors in first-degree relatives of individuals with familial premature coronary artery disease--the GENECARD project.

BACKGROUND: Hypertension, hypercholesterolemia, obesity and smoking are highly prevalent among patients with familial premature coronary artery disease (FP-CAD). Whether these risk factors equally affect other family members remains unknown. METHODS: We examined 222 FP-CAD patients, 158 unaffected sibs, 197 offspring and 94 spouses in 108 FP-CAD families (> or = 2 sibs having survived CAD diagnosed before age 51 (M)/56 (F)), and compared them to population controls. RESULTS: Unaffected sibs had a higher prevalence of hypertension (49% versus 24%, p<0.001), hypercholesterolemia (47% versus 34%, p=0.002), abdominal obesity (35% versus 24%, p=0.006) and smoking (39% versus 24%, p=0.001) than population controls. Offspring had a higher prevalence of hypertension (females), hypercholesterolemia and abdominal obesity than population controls. No difference was observed between spouses and controls. Compared to unaffected sibs, FP-CAD affected sibs had a similar risk factor profile, except for smoking, which was more prevalent (76% versus 39%, p=0.008). CONCLUSIONS: Hypertension, obesity and hypercholesterolemia are highly prevalent among first-degree relatives, but not spouses, of patients with FP-CAD. These persons deserve special medical attention due to their familial/genetic susceptibility to atherogenic metabolic abnormalities. In these families, smoking may be the trigger for FP-CAD.

Coronary MR angiography clinical applications and potential for imaging coronary artery disease.

Over the past decade, CMRA has emerged as a unique clinical imaging tool with applications in selected populations. Patients with suspected coronary artery anomalies and patients with Kawasaki disease and coronary aneurysms are among those for whom CMRA has demonstrated clinical usefulness. For assessment of patients with atherosclerotic CAD, CMRA is useful for detection of patency of bypass grafts. At centers with appropriate expertise and resources, CMRA also appears to be of value for exclusion of severe proximal multivessel CAD in selected patients. Data from multicenter trials will continue to define the clinical role of CMRA, particularly as it relates to assessment of CAD. Future developments and enhancements of CMRA promise better lumen and coronary artery wall imaging. This may become the new target in noninvasive evaluation of CAD.

Diagnostic de la maladie coronarienne stable par FFR non invasive, mythe ou réalité [Diagnosis of stable coronary artery disease with non-invasive FFR: myth or reality?].

Decision to revascularize a patient with stable coronary artery disease should be based on the detection of myocardial ischemia. If this decision can be straightforward with significant stenosis or in non-significant stenosis, the decision with intermediate stenosis is far more difficult and require invasive measures of functional impact of coronary stenosis on maximal blood (flow fractional flow reserve=FFR). A recent computer based method has been developed and is able to measure FFR with data acquired during a standard coronary CT-scan (FFRcT). Two recent clinical studies (DeFACTO and DISCOVER-FLOW) show that diagnostic performance of FFRcT was associated with improved diagnostic accuracy versus standard coronary CT-scan for the detection of myocardial ischemia although FFRcT need further development.

Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.

BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study.

BACKGROUND: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness. METHODS AND RESULTS: Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008). CONCLUSIONS: There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.