Matching between regional coronary vasodilator capacity and corresponding circumferential strain in individuals with normal and increasing body weight

Background: To define the relationship between regional coronary vasodilator capacity and myocardial circumferential strain at rest in normal weight, overweight, and obese individuals with normal global left-ventricular function. Methods and Results: Myocardial blood flow at rest and during pharmacologic vasodilation was measured with 13N-ammonia PET/CT in mL/g/minute in normal weight control (CON, n=12), overweight (OW, n=10), and obese individuals (OB, n=10). In addition, resting myocardial function was evaluated as circumferential strain (Єc, %) by MRI. Global myocardial flow reserve (MFR) did not differ significantly between CON and OW (2.98±0.96 vs 2.70±0.66, P=.290), whereas it declined significantly in OB (1.98±1.04, P=.030). Further, global Єc (%) was comparable between CON, OW, and OB (−0.24±0.03, −0.23±0.02, and −0.23±0.04) but it was lowest in OB when normalized to the rate-pressure product (NЄc: −0.31±0.06, −0.32±0.05, and −0.26±0.08). When MFR of the three major coronary territories was correlated with corresponding Єc, a positive association was observed in CON (r=0.36, P=.030), in OW (r=0.54, P=.002), and also in OB when relating NЄc to coronary vascular resistance during pharmacologic vasodilation (r=−0.46, P=.010). Conclusions: Higher coronary vasodilator capacity is related to corresponding regional circumferential strain at rest in non-obese individuals, while this is also observed for reduced MFR in obesit

Relationship between HDL Cholesterol Efflux Capacity, Calcium Coronary Artery Content, and Antibodies against ApolipoproteinA-1 in Obese and Healthy Subjects

AIMS: To explore the associations between cholesterol efflux capacity (CEC), coronary artery calcium (CAC) score, Framingham risk score (FRS), and antibodies against apolipoproteinA-1 (anti-apoA-1 IgG) in healthy and obese subjects (OS). METHODS AND RESULTS: ABCA1-, ABCG1-, passive diffusion (PD)-CEC and anti-apoA-1 IgG were measured in sera from 34 controls and 35 OS who underwent CAC score determination by chest computed tomography. Anti-apoA-1 IgG ability to modulate CEC and macrophage cholesterol content (MCC) was tested in vitro. Controls and OS displayed similar ABCG1-, ABCA1-, PD-CEC, CAC and FRS scores. Logistic regression analyses indicated that FRS was the only significant predictor of CAC lesion. Overall, anti-apoA-1 IgG were significantly correlated with ABCA1-CEC (r = 0.48, p < 0.0001), PD-CEC (r = -0.33, p = 0.004), and the CAC score (r = 0.37, p = 0.03). ABCA1-CEC was correlated with CAC score (r = 0.47, p = 0.004) and FRS (r = 0.18, p = 0.29), while PD-CEC was inversely associated with the same parameters (CAC: r = -0.46, p = 0.006; FRS: score r = -0.40, p = 0.01). None of these associations was replicated in healthy controls or after excluding anti-apoA-1 IgG seropositive subjects. In vitro, anti-apoA-1 IgG inhibited PD-CEC (p < 0.0001), increased ABCA1-CEC (p < 0.0001), and increased MCC (p < 0.0001). CONCLUSIONS: We report a paradoxical positive association between ABCA1-CEC and the CAC score, with the latter being inversely associated with PD in OS. Corroborating our clinical observations, anti-apoA-1 IgG enhanced ABCA1 while repressing PD-CEC, leading to MCC increase in vitro. These results indicate that anti-apoA-1 IgG have the potential to interfere with CEC and macrophage lipid metabolism, and may underpin paradoxical associations between ABCA1-CEC and cardiovascular risk

Structural epicardial disease and microvascular function are determinants of an abnormal longitudinal myocardial blood flow difference in cardiovascular risk individuals as determined with PET/CT

Background: The aim of this study was to determine whether epicardial structural disease may affect the manifestation of a longitudinal decrease in myocardial blood flow (MBF) or MBF difference during hyperemia in cardiovascular risk individuals, and its dependency on the flow increase. Methods and Results: In 54 cardiovascular risk individuals (at risk) and in 26 healthy controls, MBF was measured with 13N-ammonia and PET/CT in mL/g/min at rest and during dipyridamole stimulation. Computed tomography coronary angiography (CTA) was performed using a 64-slice CT of a PET/CT system. Absolute MBFs during dipyridamole stimulation were mildly lower in the mid-distal than in the mid-LV myocardium in controls (2.20±.51 vs 2.29±.51, P<.0001), while it was more pronounced in at risk with normal and abnormal CTA (1.56±.42 vs 1.91±.46 and 1.18±.34 vs 1.51±.40mL/g/min, respectively, P<.0001), resulting in a longitudinal MBF difference that was highest in at risk with normal CTA, intermediate in at risk abnormal CTA, and lowest in controls (.35±.16 and .22±.09 vs .09±.04mL/g/min, respectively, P<.0001). On multivariate analysis, log-CCS and mid-LV hyperemic MBF increase, indicative of microvascular function, were independent predictors of the observed longitudinal MBF difference (P≤.004 by ANOVA). Conclusions: Epicardial structural disease and microvascular function are important determinants of an abnormal longitudinal MBF difference as determined with PET/C

Improvement in coronary circulatory function in morbidly obese individuals after gastric bypass-induced weight loss: relation to alterations in endocannabinoids and adipocytokines

Aims To investigate the effect of surgical gastric bypass-induced weight loss and related alterations in endocannabinoids (ECs) and adipocytokine plasma levels on coronary circulatory dysfunction in morbidly obese (MOB) individuals. Methods and results Myocardial blood flow (MBF) responses to cold pressor test (CPT) from rest (ΔMBF) and during pharmacologically induced hyperaemia were measured with 13N-ammonia PET/CT in 18 MOB individuals with a body mass index (BMI) > 40 kg/m2 at baseline and after a median follow-up period of 22 months. Gastric bypass intervention decreased BMI from a median of 44.8 (inter-quartile range: 43.3, 48.2) to 30.8 (27.3, 34.7) kg/m2 (P < 0.0001). This decrease in BMI was accompanied by a marked improvement in endothelium-related ΔMBF to CPT and hyperaemic MBFs, respectively [0.34 (0.18, 0.41) from 0.03 (−0.08, 0.15) mL/g/min, P = 0.002; and 2.51 (2.17, 2.64) from 1.53 (1.39, 2.18) mL/g/min, P < 0.001]. There was an inverse correlation between decreases in plasma concentrations of the EC anandamide and improvement in ΔMBF to CPT (r = −0.59, P = 0.009), while increases in adiponectin plasma levels correlated positively with hyperaemic MBFs (r = 0.60, P = 0.050). Conversely, decreases in leptin plasma concentrations were not observed to correlate with the improvement in coronary circulatory function (r = 0.22, P = 0.400, and r = −0.31, P = 0.250). Conclusions Gastric bypass-related reduction of BMI in MOB individuals beneficially affects coronary circulatory dysfunction. The dysbalance between ECs and adipocytokines appears to be an important determinant of coronary circulatory function in obesit

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity

Aims Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. Methods and results Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with 13N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m2): control group 20≤ BMI <25 (n = 21); overweight group, 25≤ BMI <30 (n = 26); and obese group, BMI ≥30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (−0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = −0.37, P = 0.046 and r = −0.48, P = 0.008) and hyperaemic MBFs (r = −0.38, P = 0.052 and r = −0.45, P = 0.017), respectively. Conclusions Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigation

The vulnerable coronary plaque: update on imaging technologies.?

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Novel treatment strategy with direct renin inhibition against heart failure

Non-uniformity exists on heart failure definitions. Heart failure includes typical signs and symptoms deriving from alterations in left ventricular systolic or diastolic function. Systolic heart failure results from the acute or chronic reduction of the left ventricular ejection fraction. Conversely, heart failure with preserved ejection fraction is characterized by excessive myocardial fibrosis and cardiomyocyte hypertrophy that cause reduced left ventricular relaxation. Both heart failure subtypes cause identical symptoms and signs. Clinical and laboratory tests assist in the diagnosis of systolic heart failure or heart failure with preserved ejection fraction (diastolic heart failure) and can help in the identification of different causes of the disease and comorbidities. In the last two decades, the renin-angiotensin system (RAS) has been identified as a crucial regulator in all phases of systolic and diastolic heart failure. Although several studies are needed to further clarify this issue, three different levels (systemic, intracardiac and intracellular) for renin pathophysiological activity have been identified. In particular, the direct role of intracellular renin on subcellular cardiomyocyte remodeling could be considered as a very fruitful investigation field. Several ongoing clinical studies will probably clarify the role of renin inhibitors in heart failure. The ancient theory of Skeggs and coworkers on direct renin inhibition to block the RAS cascade effects could be confirmed in future studies