Kumiko Hirata

Metabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: The Northern Manhattan Study (NOMAS)

BACKGROUND Metabolic syndrome (MetS) predisposes to cardiovascular disease. Endothelial dysfunction is thought to be an important factor in the pathogenesis of atherosclerosis. We tested the hypothesis that both MetS and endothelial dysfunction are vascular risk factors and provide additive prognostic values in predicting cardiovascular events in a multiethnic community sample. METHODS The study population consisted of 819 subjects (467 female, mean age 66.5 +/- 8.8 years, 66% Hispanic) enrolled in the NOMAS. Metabolic syndrome was defined using the revised Adult Treatment Panel III criteria. Brachial artery flow-mediated dilation (FMD) was measured using high-resolution ultrasound. Endothelial dysfunction was defined as FMD <8.44% (lower 3 quartiles). Cox proportional hazards models were used to assess the effect of MetS and endothelial dysfunction on risk of cardiovascular events. RESULTS During 81 +/- 21 months of follow-up, events occurred in 84 subjects. Metabolic syndrome was independently associated with cardiovascular events in a multivariate model, including cardiovascular risk factors (adjusted hazard ratio 2.08, 95% CI 1.27-3.40). Subjects with both MetS and endothelial dysfunction were at higher risk for cardiovascular events than those with either one of them alone (adjusted hazard ratio 2.60, 95% CI 1.14-5.92). CONCLUSIONS Metabolic syndrome is associated with incident cardiovascular events. Combined use of MetS and FMD identifies those who are at higher risk of cardiovascular events. Metabolic syndrome and noninvasive FMD testing can be used concurrently for cardiovascular risk prediction.

Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction

Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the adult heart. The heart can utilize unesterified FA bound to albumin or FA obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two sources of FA are interchangeable and necessary for optimal heart function. Hearts unable to obtain FA from lipoprotein TG were able to compensate by increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had decreased expression of pyruvate dehydrogenase kinase 4 and increased cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction expression levels of genes regulating FA and glucose metabolism were acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48 h of abdominal aortic constriction. Older hLpL0 mice developed cardiac dysfunction characterized by decreased fractional shortening and interstitial and perivascular fibrosis. HLpL0 hearts had increased expression of several genes associated with transforming growth factor-β signaling. Thus, long term reduction of lipoprotein FA uptake is associated with impaired cardiac function despite a compensatory increase in glucose utilization.

Relationship between peripheral and coronary function using laser Doppler imaging and transthoracic echocardiography

Vascular dysfunction in the coronary and peripheral circulations is an early prognostic marker of future cardiovascular events. Measurements of coronary and peripheral vascular function in resistance vessels can be made, but rely on invasive procedures, which make them unsuitable for routine application. An assessment of the direct correlation between vascular responses in skin and coronary vessels has not been made previously. In 27 normal healthy subjects (18-55 years of age), we examined the relationship between peripheral and coronary vascular function. Cutaneous perfusion was measured using the non-invasive technique of laser Doppler imaging during iontophoresis of acetylcholine and sodium nitroprusside, and cutaneous vascular conductance was calculated (laser Doppler perfusion/mean arterial pressure). Coronary flow reserve was measured using transthoracic echocardiography during intravenous adenosine infusion. Mean diastolic velocities were measured at baseline and peak hyperaemic conditions from the Doppler signal recordings. CVR (coronary velocity reserve) was defined as the ratio of hyperaemic to basal mean diastolic velocities. There were significant positive correlations between CVR and cutaneous vascular conductance for acetylcholine (r=0.399, P=0.039) and sodium nitroprusside (r=0.446, P=0.020). These results support the idea that peripheral measurements of skin blood flow are representative of generalized microvascular function including that of the coronary circulation in normal healthy subjects.

Measurement of coronary vasomotor function: getting to the heart of the matter in cardiovascular research

Measurement of endothelial function in patients has emerged as a useful tool for cardiovascular research. Although no gold standard for the measurement of endothelial function exists, the measurement of flow-mediated dilation in the brachial artery, assessed with Doppler ultrasonography, is the most studied method. However, the assumption that endothelial dysfunction detected in brachial arteries is a manifestation of systemic endothelial dysfunction including the coronary circulation may not be entirely valid. Brachial and myocardial circulations differ in terms of the microvascular architecture, the pattern of blood flow and vascular resistance (e.g. shunt vessels occur in the hand but not in the myocardium), their metabolic regulation, type of receptors that contribute to humoral regulation and the pathways that are activated to induce hyperaemia. In this context, measuring coronary vasomotor function may be more useful than brachial artery measures to predict and assess potential myocardial damage related to limited vascular responsiveness. This review aims to provide an overview of the basic concept of coronary flow reserve and its different modalities of measurement, as well as its utility in cardiovascular research.

Clinical utility of new real time three-dimensional transthoracic echocardiography in assessment of mitral valve prolapse.

Background: Noninvasive and accurate assessment of mitral valve anatomy has become integral in the presurgical evaluation of patients with mitral valve prolapse (MVP). Recently developed real time three‐dimensional (RT3D) ultrasound allows online acquisition, rendering, and can provide accurate information on cardiac structures. We sought to evaluate the feasibility of RT3D for the assessment of MVP segments when compared with transesophageal echocardiography (TEE) and intraoperative findings. Methods: We examined 42 patients with MVP using RT3D, two‐dimensional (2D) transthoracic echocardiography (TTE) and TEE. For RT3D analysis, cropping planes were used to slice the 3D volume on line to visualize the prolapsed segments of the mitral valve leaflets. The mitral valve was divided into six segments based on the American Society of Echocardiographys recommendations. Two experienced cardiologists evaluated echocardiographic images. Results: Adequate RT3D images of the mitral valve were acquired in 40 out of 42 patients. The sensitivity and specificity of RT3D for defining prolapsed segments when compared with TEE were 95% and 99%, respectively (anterior leaflet: 96% and 99%, posterior leaflets: 93% and 100%, respectively). The sensitivity and specificity of TTE were 93% and 97%, respectively (anterior leaflet: 96% and 98%, posterior leaflets: 90% and 97%, respectively). Interobserver agreement for RT3D (Kappa 0.95, 95% confidence interval [CI] 0.91–1.00) was significantly greater than for TTE (Kappa 0.85, 95% CI 0.78–0.93) (P < 0.05). The elapsed time for completion of RT3D (14.4 ± 2.8 min) was shorter than for TEE (26.4 ± 4.7 min, P < 0.0001) and TTE (19.0 ± 3.1 min, P< 0.0001). Conclusions: RT3D is fast, accurate, and highly reproducible for assessing MVP.