Overt Coronary Artery Disease Research Articles

Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction.

Coronary microvascular ischaemia, cardiomyocyte injury and stiffness may play an important role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). To date, the relationship between coronary flow reserve (CFR), myocardial injury, diastolic dysfunction, and future HFpEF risk is unknown. Consecutive patients (n = 201) undergoing evaluation for suspected coronary artery disease (CAD) with stress myocardial perfusion positron emission tomography, serum troponin, and transthoracic echocardiography who did not have flow-limiting CAD or reduced left ventricular ejection fraction were identified. Patients were followed up (median 4.1 years) for cardiovascular death and hospitalization for non-fatal myocardial infarction or heart failure. Coronary flow reserve was quantified as stress/rest myocardial blood flow. Early diastolic flow (E) and relaxation (e') velocities were obtained via transmitral and tissue Doppler, respectively. Patients with impaired CFR (<2, n = 108) demonstrated linearly decreasing e' and increasing E/e' consistent with worsening diastolic function (P for trend <0.0001). A detectable troponin was associated with diastolic dysfunction only in the presence of impaired CFR (interaction P = 0.002). In adjusted analyses, impaired CFR was independently associated with diastolic dysfunction (E/e'septal > 15, adjusted OR 2.58, 95%CI 1.22-5.48) and composite cardiovascular outcomes or HFpEF hospitalization alone (adjusted HR 2.47, 95%CI 1.09-5.62). Patients with both impaired CFR and diastolic dysfunction demonstrated >five-fold increased risk of HFpEF hospitalization (P < 0.001). In symptomatic patients without overt CAD, impaired CFR was independently associated with diastolic dysfunction and adverse events, especially HFpEF hospitalization. The presence of both coronary microvascular and diastolic dysfunctions was associated with a markedly increased risk of HFpEF events.

Arterial inflammation measured by 18F-FDG-PET-CT to predict coronary events in older subjects

Background and aimsAlthough 18F-fluorodeoxyglucose (FDG) uptake has emerged as a sensitive and reliable marker of atherosclerotic inflammation, its additive predictive value for future coronary disease in older subjects is unknown. The aim of this study was to test the prognostic value of aortic inflammation detected via FDG-positron emission tomography (PET)-computed tomography (CT) in older subjects. MethodsWe retrospectively utilized the records of 309 subjects aged over 65 years, without a history of coronary artery disease, who underwent 18F-FDG-PET-CT mostly due to the clinical suspicion of cancer, but eventually turned out to be cancer-free. Target-to-background ratio (TBR) was calculated at the ascending aorta. The endpoint was occurrence of coronary heart disease (CHD) events. ResultsDuring a median follow-up of 3.9 years, 28 subjects experienced CHD events and 12 patients died due to non-CHD causes. The highest TBR tertile was associated with a high CHD event rate, accounting for death due to non-CHD causes as a competing risk (Gray test, p = 0.005). In a Fine and Gray competing risk proportional hazard regression model, TBR was associated with significantly high CHD events independently of FRS, with a hazard ratio (HR) of 1.19 per 0.1 TBR increase (p < 0.001). Likewise, a significant increase in the area under the curve (from 0.57 to 0.73, p = 0.028) and a significant improvement in net reclassification (0.42, p = 0.038) were observed when TBR was added to the model with FRS alone. ConclusionsIn older subjects with no history of malignant disease or overt coronary artery disease, arterial inflammation evaluated by FDG uptake provides information on future occurrence of coronary artery events.

Subclinical cerebrovascular disease in NAFLD without overt risk factors for atherosclerosis

Background and aimsNon-alcoholic fatty liver disease is recognized not only as part of the metabolic syndrome but also as an independent predictor of cardiovascular disease. MethodsIn this study, NMR spectroscopy method, together with perfusion techniques, was used to detect subclinical brain vascular damage in subjects with NAFLD without overt atherosclerosis risk factors (i.e. hypertension, diabetes, hypercholesterolemia, obesity). ResultsThe results suggest that subjects with histologically proven NAFLD have a reduced cerebral perfusion (CBFr) confined to limited brain areas, i.e., left semioval center and posterior cingulate cortex. No statistically significant differences in CBFr values were found, dividing the NAFLD cohort into subgroups, considering NAS score, presence/absence of NASH/fibrosis, and degree of steatosis. ConclusionsOur data suggest that NAFLD per se may be involved in cerebral atherosclerotic disease. It will be interesting to draw longitudinal studies to determine whether these changes could evolve in more serious cerebral injury.

The Influence of Dietary Components on Early Signs of Atherosclerosis in Apparently Healthy Young-adult Males: An Observational Study of 615 Subjects.

The literature shows that a healthy diet, rich in fruits and vegetables, has positive effects on overall cardiovascular risk, protecting against atherosclerosis. A cross sectional study in a population of apparently healthy young-adult men with the aim of investigating dietary determinants of early atherosclerosis, assessed by measuring carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) of the brachial artery. 615 males (mean age ± SD: 40.8±9.8 years) without overt atherosclerosis were evaluated. Dietary intake was quantified by the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Intake of antioxidants was expressed in relation to total caloric intake. Neither absolute, recommended daily allowance or weight-related values of nutritional intake variables were associated with cIMT. Vitamin E to total calories intake (odds ratio, OR=0.08, 95%CI=0.03-0.89) was inversely associated with impaired FMD. Non-nutritional correlates of FMD <10% were: age (OR=1.02, 95%CI=1.0-1.05) and waist circumference (OR=1.03, 95%CI=1.0-1.06), and those of cIMT >0.8 mm were age (OR=1.10, 95%CI=1.05-1.15), pack-years (OR=1.02, 95%CI=1.0-1.04), C-reactive protein (OR=1.17, 95%CI=1.04-1.33) and total cholesterol (OR=1.01, 95%CI=1.0-1.02). Differences in the factors correlating with cIMT >0.8 mm and FMD <10% might have implications for cardiovascular risk reduction. A lower antioxidant to caloric intake ratio might be a risk factor for impaired FMD.

1671The 2MACE score predicts major adverse cardiovascular outcomes in patients with atrial fibrillation without overt coronary artery disease

1671The 2MACE score predicts major adverse cardiovascular outcomes in patients with atrial fibrillation without overt coronary artery disease

Increased phagocytic NADPH oxidase activity associates with coronary artery calcification in asymptomatic men

Vascular calcification is a common feature in atherosclerosis and associates with cardiovascular events. Oxidative stress may be involved in the pathogenesis of vascular calcification. Previous studies have shown that the phagocytic NADPH oxidase is associated with atherosclerosis. The objective of the present study was to investigate the association between phagocytic NADPH oxidase-mediated superoxide production and coronary artery calcium (CAC). NADPH oxidase-mediated superoxide production was determined by chemiluminescence and CAC by computed tomography in 159 asymptomatic men free of overt clinical atherosclerosis. Multivariate linear regression analyses were used to assess the relationship between CAC and NADPH oxidase-mediated superoxide production. Compared with individuals in the lowest score of CAC (= 0 Agatston units), those in the upper score (>400 Agatston units) showed higher superoxide production (p < 0.05). In correlation analysis, superoxide production positively (p < 0.01) correlated with CAC, which in multivariate analysis remained significant after adjusting for age, HDL-cholesterol, triglycerides, body mass index, smoking, arterial hypertension and diabetes mellitus. In conclusion, in a population of men without clinically overt atherosclerotic disease, increased NADPH oxidase-mediated superoxide production associated with enhanced CAC. Albeit descriptive, these findings suggest a potential involvement of phagocytic NADPH oxidase-mediated oxidative stress in CAC.

Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease: A single-center cross-sectional study.

Recently, the pathogenic role of uric acid (UA) in both systemic metabolic and atherosclerotic diseases has been investigated. We sought to determine the independent correlation between serum UA levels and coronary artery calcification, as a marker of subclinical atherosclerosis. A total of 4188 individuals without prior coronary artery disease or urate-deposition disease were included. All of the participants underwent multidetector computed tomography (MDCT) for the evaluation of coronary artery calcification (CAC) during their health check-ups. The subjects were divided into thre groups according to CAC scores (group 1: 0; group 2: 1-299; group 3: ≥300). After controlling for other confounders, serum UA levels were found to be positively associated with increasing CAC scores (P = 0.001). Adjusted mean serum UA levels in each CAC group were estimated to be 5.2 ± 0.1 mg/dL, 5.3 ± 0.1 mg/dL, and 5.6 ± 0.2 mg/dL from groups 1, 2, and 3, respectively. Subsequent subgroup analyses revealed that this positive association was only significant in participants who were male, relatively older, less overweight, and did not have diabetes mellitus (DM), hypertension, smoking history, or renal dysfunction. In conclusion, serum uric acid levels were independently associated with CAC score severity and this finding is particularly relevant to the subjects who were male, relatively older, less overweight (body mass index < 25 kg/m), and without a history of DM, hypertension, smoking, or renal dysfunction.

Effects of increased left ventricular wall thickness on the myocardium in severe aortic stenosis with normal left ventricular ejection fraction: Two- and three-dimensional multilayer speckle tracking echocardiography.

The aim of this study was to determine the capability of real time three-dimensional echocardiography (RT3DE) and two-dimensional (2D) multilayer speckle tracking echocardiography (MSTE) for evaluation of early myocardial dysfunction triggered by increased left ventricular (LV) wall thickness in severe aortic stenosis (AS) with normal LV ejection fraction (EF≥55%). Conventional, RT3D STE and 2D MSTE were performed in 45 patients (mean 68.9±9.0years) with severe AS (aortic valve area <1cm2 , aortic velocity Vmax >4m/s or mean PG >40mmHg) and normal left ventricular ejection fraction (LVEF) without overt coronary artery disease and in 18 age-, sex-matched healthy controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were calculated using RT3DE and MSTE. The severe AS group had lower 3D GLS, GRS, GAS and 2D epicardium, and mid-wall and endocardium GLS compared to healthy controls. In MSTE analysis, 2D LS and CS values decreased from the endocardial layer toward the epicardial layer. Severe AS patients with increased LV wall thickness had lower 3D GLS and 2D epicardium, and mid-wall and endocardium GLS compared with severe AS patients without LV wall thickening. GLS on RT3D STE was correlated with GLS on 2D MSTE, left ventricular mass index, LVEF, left atrial volume index, and lnNT-proBNP. RT3DE and 2D MSTE can be used to identify subtle contractile dysfunction triggered by increased LV wall thickness in severe AS with normal LVEF. Therefore, RT3D STE and 2D MSTE may provide additional information that can facilitate decision-making regarding severe AS patients with increased LV wall thickness and normal LV function.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

PS 08-66 THE IMPACT OF HYPERTENSION AND LV DIMENSION ON LV SUBCLINICAL DYSFUNCTION IN MORE THAN MODERATE TO SEVERE ASYMPTOMATIC AORTIC REGURGITATION WITH NORMAL LV SYSTOLIC FUNCTION

Objective: LV systolic function and end-systolic, end-diastolic LV dimension (LVESD, LVEDD) are regarded as important parameters when considering AV surgery for patients with asymptomatic AR. Patients with asymptomatic AR show subclinical LV longitudinal axis dysfunction, with more attenuation demonstrated in hypertensive than in normotensive patients. The aims of our study were to detect signs of subclinical LV dysfunction and to determine the impact of hypertension and LV dimension on LV systolic dysfunction in patients with chronic asymptomatic AR using multilayer-speckle-tracking echocardiography (MSTE). Design and method: Conventional echocardiography and 2D MSTE were performed in 37 normal patients and 85 patients (mean 53.6 ± 13.6 yr) with more than moderate to severe chronic AR (vena contracta > 0.6 cm, ERO > 0.3 cm2 or regurgitant volume > 60mL) and normal LVEF (≥ 50%) and without overt coronary artery disease. Multilayer-Global longitudinal strain (GLS) was calculated by 2D MSTE. Results: Patients were divided into each of four groups by the 65 mm of LVEDD or the 50 mm of LVESD by the current ACC/AHA VHD guideline; group 0: LVESD ≤ 50 mm or LVEDD ≤ 65 mm and HTN (−), group 1: LVESD ≤ 50 mm or LVEDD ≤ 65 mm and HTN (+), group 2: LVESD > 50 mm or LVEDD > 65 mm and HTN (−), group 3; LVESD > 50 mm or LVEDD > 65 mm and HTN (+). Clinical characteristics, IVSd and LVPWd were no significant differences between four groups. LVMI was the largest in the LVEDD > 65 mm or LVESD > 50 mm and HTN group. And, GLS was the lowest in the LVEDD > 65 mm or LVESD > 50 mm and HTN group. GLS of endocardium, mid-wall, and epicardium was reduced when the LVEDD was more than 65 mm or LVESD was more than 55 mm. Conclusions: Patients with asymptomatic chronic AR showed subclinical LV longitudinal axis dysfunction, with more attenuation demonstrated in hypertensive than in normotensive and with the LVEDD > 65 mm or LVESD > 50 mm. Our results suggest that MSTE may compliment evaluation of patients with asymptomatic chronic AR.

Smoking and Cardiac Structure and Function in the Elderly: The ARIC Study (Atherosclerosis Risk in Communities).

Cigarette smoking has been associated with higher risk of incident heart failure independent of coronary artery disease, but the impact of tobacco use on cardiac structure and function in the general population is uncertain. This study evaluated the relationship between smoking and echocardiographic measures in a large elderly cohort. We studied 4580 participants free of overt coronary artery disease, heart failure, and significant valvular disease from the fifth visit of the ARIC study (Atherosclerosis Risk in Communities) who underwent transthoracic echocardiography. Participants were classified into 3 categories based on self-reported smoking habits: never (43.2%), former (50.5%), and current smokers (6.3%). Pack-years and years of smoking were also estimated. Compared with never smokers, current smokers had greater left ventricular (LV) mass index (80.4±1.1 versus 76.7±0.4 g/m(2); P<0.001), LV mass/volume ratio (1.93±0.03 versus 1.83±0.03 g/mL; P<0.001), higher prevalence of LV hypertrophy (15% versus 9%; P=0.008), and worse diastolic function, as reflected by higher E/E' ratio (11.7±0.2 versus 10.9±0.1; P<0.001), after adjusting for potential confounding factors. In contrast, former smokers showed similar echocardiographic features when compared with never smokers. Furthermore, estimated pack-years and years of smoking, measures of cumulative cigarette exposure, were associated with greater LV mass index, LV mass/volume ratio, and worse diastolic function (higher E/E' ratio) in current smokers after multivariable analysis (all P<0.01). Active smoking and cumulative cigarette exposure were associated with subtle alterations in LV structure and function in an elderly, community-based population free of overt coronary artery disease and heart failure.

Combination of Visual and Metabolic Markers in Assessment of Probability of Presence and Severity of Atherosclerosis of Coronary Arteries

to assess possibilities of the use of biochemical markers combined with data of methods of imaging of arterial atherosclerotic lesions for evaluation of risk of presence and severity of coronary atherosclerosis. We enrolled into this study patients (n=205, 136 men, 69 women, age 33-85 years, 94% on statin therapy) who underwent coronary angiography and carotid artery ultrasound dopplerography. Examination included determination of parameters of lipid profile and carbohydrate metabolism, markers of inflammation and metabolism of visceral adipose tissue. The severity of carotid artery atherosclerosis was estimated using mean common carotid artery intima-media thickness and atherosclerotic plaques presence. Severity of coronary atherosclerosis was evaluated using Gensini score. We found association between a number of biomarkers and severity of coronary artery involvement. Presence of coronary atherosclerosis (Gensini score >0) was associated with male sex, carotid artery stenosis >45%, and adiponectin level <8.0 pg/ml. Overt coronary atherosclerosis (Gensini score more or equal 35) significantly correlated with intima-media thickness more or equal 0.9 mm, C-reactive protein level >3.0 mg/l and adiponectin level <8.0 pg/ml.

Influence of cigarette smoking on cardiac biomarkers: the Atherosclerosis Risk in Communities (ARIC) Study.

Cigarette smoking has been associated with incident heart failure independent of coronary artery disease (CAD), but the mechanisms linking smoking to cardiac damage are not well understood. This study sought to evaluate the relationship between smoking and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively, biomarkers of myocardial wall stress and injury, in a large community-based cohort. We examined the association between smoking history and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4 (1996-1998), as well as the association with change in these biomarkers from Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher cumulative cigarette exposure, assessed by total pack-years, was associated with elevated levels of NT-proBNP (P < 0.001) and hs-TnT (P = 0.01) among ever smokers in multivariable analyses adjusted for potential confounders. After 15 years of follow-up, participants who were active smokers at Visit 4 had greater incidence of elevated NT-proBNP {adjusted proportion = 48% [95% confidence interval (CI) 41, 54] vs. 35 (95% CI 32, 39); P = 0.006} and hs-TnT [adjusted proportion = 32% (95% CI 26, 38) vs. 23 (95% CI 20, 26); P = 0.021] compared with never smokers, adjusting for baseline and follow-up covariates. In a large community-based cohort free of overt CAD and heart failure, cigarette smoking was associated with biomarkers of myocardial wall stress and injury at baseline as well as with a continued measurable increase in these biomarkers after 15 years of follow-up.

Direct Cervical Carotid Angioplasty with Flow Reversal: A Single-Center Report from the Roadster Trial

Carotid stent and/or angioplasty (CAS) via the transfemoral route with distal protection carries twice the risk of stroke and/or death when compared with carotid endarterectomy (CEA) in multiple randomized trials. Potential causes for this include disadvantaged aortic arch anatomy and the need to traverse the lesion to place a distal protection device. This report describes the technique and our experience with direct CAS using flow reversal for embolic protection. University of California at Los Angeles (UCLA) division of Vascular and Endovascular surgery was a participant in the multi-institutional Roadster Trial of high-risk patients. We are reporting on our experience with 8 patients who met high-risk criteria. Using a small supraclavicular cutdown, the Michi sheath from Silk Road Medical was inserted into the common carotid artery. This provides a working channel for internal CAS as well as a side port to reverse and divert blood flow to the femoral vein, for embolic protection. All patients qualified as medically high risk because of a combination of factors including advanced age, smoking history, hypertension, diabetes, coronary artery disease, or hostile neck anatomy. All 8 patients had 3 or more risk factors including age >75 years (6 of 8), smoking (6 of 8), hypertension (7 of 8), overt coronary artery disease (4 of 8), diabetes (2 of 8), and chronic obstructive pulmonary disease (1 of 8). All stenoses were in the 80-99% category, and all were asymptomatic. All patients tolerated temporary clamping with flow reversal with no electroencephalogram changes. There were no deaths, strokes, transient ischemic attacks, or myocardial infarctions. All patients were discharged on the first postoperative day. Follow-up ranged from 7 to 21months. One patient developed in-stent restenosis (asymptomatic). Direct CAS with flow reversal appears to be a safe, less invasive alternative to CEA.

Carotid Artery End-Diastolic Velocity and Future Cerebro-Cardiovascular Events in Asymptomatic High Risk Patients.

Background and ObjectivesPrognostic value of additional carotid Doppler evaluations to carotid intima-media thickness (IMT) and plaque has not been completely evaluated.Subjects and MethodsA total of 1119 patients with risk factors for, but without, overt coronary artery disease (CAD), who underwent both carotid ultrasound and Doppler examination were included in the present study. Parameters of interest included peak systolic and end-diastolic velocities, resistive indices of the carotid arteries, IMT, and plaque measurements. The primary end-point was all-cause cerebro-cardiovascular events (CVEs) including acute myocardial infarction, coronary revascularization therapy, heart failure admission, stroke, and cardiovascular death. Model 1 covariates comprised age and sex; Model 2 also included hypertension, diabetes and smoking; Model 3 also had use of aspirin and statin; and Model 4 also included IMT and plaque.ResultsThe mean follow-up duration was 1386±461 days and the mean age of the study population was 60±12 years. Amongst 1119 participants, 43% were women, 57% had a history of hypertension, and 23% had diabetes. During follow-up, 6.6% of patients experienced CVEs. Among carotid Doppler parameters, average common carotid artery end-diastolic velocity was the independent predictor for future CVEs after adjustments for all models variables (HR 0.95 per cm/s, 95% confident interval 0.91-0.99, p=0.034 in Model 4) and significantly increased the predictive value of Model 4 (global χ2=59.0 vs. 62.8, p=0.029).ConclusionCarotid Doppler measurements in addition to IMT and plaque evaluation are independently associated with future CVEs in asymptomatic patients at risk for CAD.

Association of Depression and Stress in Acute Myocardial Infarction: a case-control study

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Psychosocial factors have been reported to be independently associated with coronary artery disease (CAD). However, the stress variable is still sub detailed and there are few studies that used coronary angiography (CA) to assess CAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To compare levels of depression, stress and stressful life events in three groups of individuals: post-MI (Myocardial Infarction) patients; patients presenting symptoms and no previous MI, who underwent cardiac catheterization and had non-significant obstructive CAD and individuals with no symptoms of cardiac disease or others diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We conducted a case-control study, with two cases groups and one control group. The study included 105 patients with recent Myocardial Infarction (MI group), 101 patients with cardiac symptoms and normal CA (CS group), and 100 patients without symptoms of disease (NS group). Multivariate logistic regression was used to assess, stress and vital events, with an Odds Ratio of 95% confidence interval (CI), controlling for age, sex, education level, income, social support group, Body Mass Index (BMI), sedentary lifestyle and family history of MI or sudden death.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;MI patients group showed depression with an OR= 4.47(95% CI, 2:36 to 8:46, p&amp;lt;.001), and stress OR= 5.37(95%CI, 2.94-9.78, p &amp;lt;.001) whereas CS group showed depression: OR= 6.95(95%CI, 3.64-13.28, p &amp;lt;.001) and stress: OR = 9.18 (95%CI, 4.73-17.82, p &amp;lt;.001) compared to patients without symptoms. After adjusting for risk factors: age, sex, education, income, social support, obesity, sedentary lifestyle, family history of MI or sudden death, the OR showed the following variation: in the MI group, depression OR= 2.51 (95%CI, 1:05 to 5:98, p = .038), stress, OR= 8.76(95%CI, 3:48 to 22:01, p &amp;lt;.001), and CS group, depression OR= 3.25(95%CI, 1.40-7.55,p &amp;lt;01) and stress OR= 12.24 (95%, CI, 4.81-31.14, p &amp;lt;.001). The raised effect of variable stress after adjustment was promoted by the age, sex and physical inactivity variables, and did not affect the significance level (p &amp;lt;.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study has demonstrated that subjects with cardiac symptoms without overt CAD, present similar depression and/or stress levels than post-MI patients. And also, post-MI patients and CS patients have more stress and depression than controls, even when adjusted for age, sex, education level, family income, social support, obesity, sedentary lifestyle and family history of MI and / or sudden death.&lt;/p&gt;

The amount of C1q-adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal-medial layer of blood vessels of coronary artery disease patients.

BackgroundThe complement component C1q triggers activation of the classical immune pathway and can bind to adiponectin (APN). Recently, some studies have been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis and coronary artery disease (CAD). We assessed the relationships between C1q related variables and the severity of CAD, and investigated the localization of the C1q–APN complex.MethodsThe sample included 153 subjects comprising healthy controls and patients with subclinical or overt CAD. We measured the serum concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the amount of C1q–APN complex. We identified the sites of C1q–APN complex deposition in various adipose tissues and blood vessels.ResultsSerum concentrations of C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the severity of coronary stenosis. The amount of C1q–APN complex was significantly higher in patients with CAD compared with controls. C1q and APN co-localized in perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and the internal mammary artery of patients with severe CAD.ConclusionsSerum C1q concentration and the C1q/HMW-APN ratio were independent markers of coronary artery stenosis. The amount of C1q–APN complex was significantly greater in serum from CAD patients. C1q and APN co-localized to perivascular areas in adipose tissue and blood vessels. The association between the increased amount of the C1q–APN complex and CAD should be investigated further.

Assessment of Endoplasmic Reticulum Stress by Graded Sarcoplasmic Reticulum Ca2+ Store Depletion in Coronary Smooth Muscle

This study examined the threshold of sarcoplasmic reticulum (SR) Ca2+ store depletion necessary for induction of endoplasmic reticulum (ER) stress in coronary smooth muscle cells (CSM). Coronary arteries from Ossabaw swine with and without coronary artery disease (CAD) were sectioned into arterial rings and denuded of endothelium for assessment of ER stress. Phosphorylation of eukaryotic initiation factor 2α was examined by immunoblot as an index of ER stress and was elevated in CAD arteries, compared to healthy. CSM were enzymatically isolated and loaded with the fluorescent intracellular Ca2+ indicator, fura‐2. In arteries with overt CAD, CSM from atherosclerotic plaques were isolated separately from the medial layer. The SR Ca2+ store was released with caffeine in Ca2+‐free physiologic salt solution (0Ca‐PSS) and the resultant transient rise in cytosolic Ca2+ was examined as an index of SR Ca2+ store. The SR Ca2+ store was increased ~1.5‐fold in CSM from arteries with mild CAD compared to healthy, but was decreased in overt CAD. Sarco/endoplasmic reticulum Ca2+ ATPase activity as assessed by recovery of cytosolic Ca2+ below baseline followed the same pattern. Following release with 1, 5, or 10 mM caffeine, the SR Ca2+ store was clamped in 0Ca‐PSS for 30 minutes, after which the remainder of the SR Ca2+ was released. This SR Ca2+ store release was assessed as a percentage of maximum. The SR Ca2+ store was depleted in a dose‐dependent manner, indicating the feasibility of clamping SR Ca2+ independent of cytosolic Ca2+. Together, these results indicate that CSM display ER stress in CAD and that SR Ca2+ store is decreased in overt CAD, providing clues to the mechanisms behind CSM changes underlying CAD progression.(Support: NIH HL062552)

Quantification of coronary flow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes.

Patients with left ventricular systolic dysfunction frequently show abnormal coronary vascular function, even in the absence of overt coronary artery disease. Moreover, the severity of vascular dysfunction might be related to the aetiology of cardiomyopathy.We sought to determine the incremental value of assessing coronary vascular dysfunction among patients with ischaemic (ICM) and non-ischaemic (NICM) cardiomyopathy at risk for adverse cardiovascular outcomes. Coronary flow reserve (CFR, stress/rest myocardial blood flow) was quantified in 510 consecutive patients with rest left ventricular ejection fraction (LVEF) ≤45% referred for rest/stress myocardial perfusion PET imaging. The primary end point was a composite of major adverse cardiovascular events (MACE) including cardiac death, heart failure hospitalization, late revascularization, and aborted sudden cardiac death.Median follow-up was 8.2 months. Cox proportional hazards model was used to adjust for clinical variables. The annualized MACE rate was 26.3%. Patients in the lowest two tertiles of CFR (CFR ≤ 1.65) experienced higher MACE rates than those in the highest tertile (32.6 vs. 15.5% per year, respectively, P = 0.004), irrespective of aetiology of cardiomyopathy. Impaired coronary vascular function, as assessed by reduced CFR by PET imaging, is common in patients with both ischaemic and non-ischaemic cardiomyopathy and is associated with MACE.

Usefulness of N-terminal Pro–brain Natriuretic Peptide and Myocardial Perfusion in Asymptomatic Adults (from the Multi-Ethnic Study of Atherosclerosis)

This study sought to investigate the relation between myocardial perfusion and N-terminal pro-brain natriuretic peptide (NT-proBNP) in asymptomatic adults without overt coronary artery disease. NT-proBNP is a cardiac neurohormone secreted from the ventricles in response to ventricular volume expansion and pressure overload and may also be elevated in the setting of reduced myocardial perfusion. We hypothesized that reduced myocardial perfusion reserve (MPR) would be associated with elevated NT-proBNP in participants free of overt cardiovascular disease. MPR was measured by cardiac magnetic resonance, before and after adenosine infusion, in 184 MESA participants (mean age 60 ± 10.4, 58% white, 42% Hispanic, 44% women) without overt cardiovascular disease. MPR was modeled as hyperemic myocardial blood flow (MBF) adjusted for MBF at rest. A linear regression analysis, adjusted for demographics, established cardiovascular risk factors, left ventricular mass, coronary calcium score, body mass index, and medications, was used to determine the association between MPR and NT-proBNP. Participants with low hyperemic MBF were more likely to be older, male, diabetic, and have higher blood pressure and higher coronary artery calcium score. Mean hyperemic MBF was 3.04 ± 0.829 ml/min/g. MPR was inversely associated with NT-proBNP levels. In a fully adjusted model, every 1-SD decrement in MPR was associated with a 21% increment in NT-proBNP (p = 0.04). In conclusion, MPR is inversely associated with NT-proBNP level in this cross-sectional study of asymptomatic adults free of overt coronary artery disease, suggesting that higher NT-proBNP levels may reflect subclinical myocardial microvascular dysfunction.