Jen-Yuan Kuo

Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks

BACKGROUND Coronary atherosclerosis has traditionally been proposed to be associated with several cardiovascular risk factors and anthropometric measures. However, clinical data regarding the independent value of visceral adipose tissue in addition to such traditional predictors remains obscure. MATERIALS AND METHODS We subsequently studied 719 subjects (age: 48.1±8.3 years, 25% females) who underwent multidetector computed tomography (MDCT) for coronary calcium score (CCS) quantification. Baseline demographic data and anthropometric measures were taken with simultaneous body fat composition estimated. Visceral adipose tissue of pericardial and thoracic peri-aortic fat was quantified by MDCT using TeraRecon Aquarius workstation (San Mateo, CA). Traditional cardiovascular risk stratification was calculated by metabolic (NCEP ATP III) and Framingham (FRS) scores and high-sensitivity CRP (Hs-CRP) was taken to represent systemic inflammation. The independent value of visceral adipose tissue to systemic inflammation and CCS was assessed by utilizing multivariable regression analysis. RESULTS Of all subjects enrolled in this study, the mean values for pericardial and peri-aortic adipose tissue were 74.23±27.51 and 7.23±3.69ml, respectively. Higher visceral fat quartile groups were associated with graded increase of risks for cardiovascular diseases. Both adipose burdens strongly correlated with anthropometric measures including waist circumference, body weight and body mass index (all p<0.001). In addition, both visceral amount correlates well with ATP and FRS scores, all lipid profiles and systemic inflammation marker in terms of Hs-CRP (all p<0.001). After adjustment for baseline variables, both visceral fat were independently related to Hs-CRP levels (all p<0.05), but only pericardial fat exerted independent role in coronary calcium deposit. CONCLUSION Both visceral adipose tissues strongly correlated with systemic inflammation beyond traditional cardiovascular risks and anthropometric measures, though only pericardial fat exerted independent role in coronary calcium deposit. Our data suggested that visceral adipose tissue may thus contribute to systemic inflammation and play an independent role in the pathogenesis of atherosclerosis.

Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography.

BACKGROUND Epicardial adipose tissue (EAT) measured by echocardiography has been proposed to be associated with metabolic syndrome and increased cardiovascular risks. However, its independent association with fatty liver disease and systemic inflammation beyond clinical variables and body fat remains less well known. METHODS The relationships between EAT and various factors of metabolic derangement were retrospectively examined in consecutive 359 asymptomatic subjects (mean age, 51.6 years; 31% women) who participated in a cardiovascular health survey. Echocardiography-derived regional EAT thickness from parasternal long-axis and short-axis views was quantified. A subset of data from 178 randomly chosen participants were validated using 16-slice multidetector computed tomography. Body fat composition was evaluated using bioelectrical impedance from foot-to-foot measurements. RESULTS Increased EAT was associated with increased waist circumference, body weight, and body mass index (all P values for trend = .005). Graded increases in serum fasting glucose, insulin resistance, and alanine transaminase levels were observed across higher EAT tertiles as well as a graded decrease of high-density lipoprotein (all P values for trend <.05). The areas under the receiver operating characteristic curves for identifying metabolic syndrome and fatty liver disease were 0.8 and 0.77, with odds ratio estimated at 3.65 and 2.63, respectively. In a multivariate model, EAT remained independently associated with higher high-sensitivity C-reactive protein and fatty liver disease. CONCLUSIONS These data suggested that echocardiography-based epicardial fat measurement can be clinically feasible and was related to several metabolic abnormalities and independently associated fatty liver disease. In addition, EAT amount may contribute to systemic inflammation beyond traditional cardiovascular risks and body fat composition.

Relation of Carotid Artery Diameter With Cardiac Geometry and Mechanics in Heart Failure With Preserved Ejection Fraction

Background Central artery dilation and remodeling are associated with higher heart failure and cardiovascular risks. However, data regarding carotid artery diameter from hypertension to heart failure have remained elusive. We sought to investigate this issue by examining the association between carotid artery diameter and surrogates of ventricular dysfunction. Methods and Results Two hundred thirteen consecutive patients including 49 with heart failure and preserved ejection fraction (HFpEF), 116 with hypertension, and an additional 48 healthy participants underwent comprehensive echocardiography and tissue Doppler imaging. Ultrasonography of the common carotid arteries was performed for measurement of intima‐media thickness and diameter (CCAD). Cardiac mechanics, including LV twist, were assessed by novel speckle‐tracking software. A substantial graded enlargement of CCAD was observed across all 3 groups (6.8±0.6, 7.7±0.73, and 8.7±0.95 mm for normal, hypertension, and HFpEF groups, respectively; ANOVA P<0.001) and correlated with serum brain natriuretic peptide level (R2=0.31, P<0.001). Multivariable models showed that CCAD was associated with increased LV mass, LV mass‐to‐volume ratio (β‐coefficient=10.9 and 0.11, both P<0.001), reduced LV longitudinal and radial strain (β‐coeffficient=0.81 and −3.1, both P<0.05), and twist (β‐coefficient=−0.84, P<0.05). CCAD set at 8.07 mm as a cut‐off had a 77.6% sensitivity, 82.3% specificity, and area under the receiver operating characteristic curves (AUROC) of 0.86 (95% CI 0.80 to 0.92) in discriminating HFpEF. In addition, CCAD superimposed on myocardial deformation significantly expanded AUROC (for longitudinal strain, from 0.84 to 0.90, P of ΔAUROC=0.02) in heart failure discrimination models. Conclusions Increased carotid artery diameter is associated with worse LV geometry, higher brain natriuretic peptide level, and reduced contractile mechanics in individuals with HFpEF.

The normal limits, subclinical significance, related metabolic derangements and distinct biological effects of body site-specific adiposity in relatively healthy population.

Background The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized. Materials and Methods In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines. Results TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05). Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05), serum insulin (ß-coef.:0.17, p<0.05) and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05). These relationships persisted after adjustment in multivariable models (all p<0.05). A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74–0.83) to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05). Conclusion In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and subclinical atherosclerosis in a relatively healthy population.

High pericardial and peri-aortic adipose tissue burden in pre-diabetic and diabetic subjects

BackgroundCentral obesity in relation to insulin resistance is strongly linked to the development of type 2 diabetes. However, data regarding the association between pericardial and peri-aortic adiposity, a potential estimate of visceral adipose tissue burden, and pre-diabetes status remains unclear.The aim of this study was to examine whether the degree of pericardial and thoracic peri-aortic adipose tissue, when quantified by multi-detector computed tomography (MDCT), differs significantly in a normal, pre-diabetic, and overtly diabetic population.MethodsWe studied 562 consecutive subjects including 357 healthy, 155 pre-diabetic, and 50 diabetic patients selected from participants who underwent annual health surveys in Taiwan. Pre-diabetes status was defined by impaired fasting glucose or impaired glucose intolerance according to American Diabetes Association guidelines. Pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Body fat composition, serum high-sensitivity C-reactive protein (hs-CRP) level and insulin resistance (HOMA-IR) were also assessed.ResultsPatients with diabetes and pre-diabetes had greater volume of PCF (89 ± 24.6, 85.3 ± 28.7 & 67.6 ± 26.7 ml, p < 0.001) as well as larger TAT (9.6 ± 3.1 ml vs 8.8 ± 4.2 & 6.6 ± 3.5 ml, respectively, p < 0.001) when compared to the normal group, although there were no significant differences in adiposity between the diabetic and pre-diabetic groups. For those without established diabetes in our study, increasing TAT burden, but not PCF, appear to correlate with insulin resistance (HOMA-IR) and hs-CRP in the multivariable models.ConclusionsPre-diabetic and diabetic subjects, compared to normoglycemia, were associated with significantly higher pericardial and peri-aortic adipose tissue burden. In addition, visceral fat accumulation adjacent to the thoracic aorta seemed to exert a significant impact on insulin resistance and systemic inflammation.

Independent Effects of Body Fat and Inflammatory Markers on Ventricular Geometry, Midwall Function, and Atrial Remodeling

The effect of body fat distribution on left ventricular (LV) mass and geometry has been recently recognized. However, data regarding circulating inflammatory markers in relation to regional visceral fat deposits, which are metabolically active tissues that can impact cardiac structural remodeling, remain sparse.

Relation of carbohydrate antigen-125 to left atrial remodeling and its prognostic usefulness in patients with heart failure and preserved left ventricular ejection fraction in women.

Carbohydrate antigen-125 (CA-125) has recently been reported to correlate with the severity of systolic heart failure (HF). However, the association between this marker and HF with preserved ejection fraction (HFpEF) remains elusive. We studied 158 consecutive women with preserved ejection fraction, who were categorized into 3 groups: those with HF (HFpEF group, n = 35), those with ≥1 cardiovascular risk (at-risk group, n = 78), and 45 normal controls (n = 45). All subjects underwent echocardiography with serum N-terminal pro-brain type natriuretic peptide (NT-ProBNP), CA-125 level, and other tumor markers obtained. HFpEF group showed significantly greater baseline levels of CA-125 and NT-ProBNP than both normal and at-risk groups (p <0.05). In addition, the serum CA-125 level correlated with the maximum left atrial volume (r = 0.24, p = 0.002). During a mean follow-up of 828.1 days (interquartile range 38 to 1,504.5), those with CA-125 levels >17.29 U/ml had a greatest incidence of HF hospitalization (hazard ratio 6.2, p <0.01) and remained an independent prognosticator in the multivariate Cox models. CA-125 superimposed on NT-ProBNP successfully expanded the receiver operating characteristic curve further in predicting HF hospitalization (area under curve 0.72 to 0.82, c-statistic 0.0049). In conclusion, serum CA-125 might serve as a novel biomarker for HFpEF and predicting HF hospitalization in women.

Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population.

Background Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. Materials and Methods We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004–2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. Results In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (–0.1%/decade) with aging was apparent in women after multi-variate adjustment (–0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. Conclusions Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure.

The relationship among atrium electromechanical interval, insulin resistance, and metabolic syndrome.

BACKGROUND Metabolic syndrome (MS) is an important risk factor of atrial fibrillation. However, an understanding of the adverse effects of MS on left atrial (LA) functional assessment in terms of electromechanical interval, a convenient parameter that can reflect the process of LA remodelling, has been lacking. The goal of this study was to investigate the association between electromechanical interval and MS. METHODS In all, 337 patients (91 with MS) with mean age of 51.9 ± 9.0 years were enrolled. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III score. Insulin resistance was assessed by the homeostasis model assessment-insulin resistance method. The electromechanical interval, defined as the time from initiation of P wave deflection to peak of mitral inflow Doppler A wave (PA-PDI), was measured. RESULTS Patients with MS had significantly longer PA-PDI intervals compared with those of patients without MS (131.0 ± 12.4 milliseconds vs. 123.2 ± 14.0 milliseconds, P < 0.001). Longer PA-PDI intervals were observed in subjects with higher metabolic scores (P < 0.05). In patients with small LA size, PA-PDI intervals, but not LA dimensions, were significantly different between groups with and without MS (P < 0.05). Additionally, PA-PDI interval was positively correlated with insulin resistance (r = 0.267, P < 0.001). CONCLUSIONS PA-PDI intervals were longer in patients with MS compared with those of patients without MS and tracked with insulin resistance. PA-PDI may be a useful clinical parameter to represent the degree of atrial remodelling in subjects with metabolic derangements.

Relation of Myocardial Systolic Mechanics to Serum Ferritin Level as a Prognosticator in Thalassemia Patients Undergoing Repeated Transfusion

Myocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known.