Marit Granér

Cardiac steatosis associates with visceral obesity in nondiabetic obese men.

BACKGROUND Liver fat and visceral adiposity are involved in the development of the metabolic syndrome (MetS). Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. The aim of this study was to explore components of cardiac steatosis and their relationship to intra-abdominal ectopic fat deposits and cardiometabolic risk factors in nondiabetic obese men. METHODS Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy, and visceral adipose (VAT), abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by magnetic resonance imaging in 37 men with the MetS and in 40 men without the MetS. RESULTS Myocardial and hepatic TG contents, VAT, SAT, epicardial fat volumes, and pericardial fat volumes were higher in men with the MetS compared with subjects without the MetS (P < .001). All components of cardiac steatosis correlated with SAT, VAT, and hepatic TG content and the correlations seemed to be strongest with VAT. Myocardial TG content, epicardial fat, pericardial fat, VAT, and hepatic TG content correlated with waist circumference, body mass index, high-density lipoprotein cholesterol TGs, very low-density lipoprotein-1 TGs, and the insulin-resistance homeostasis model assessment index. VAT was a predictor of TGs, high-density lipoprotein cholesterol, and measures of glucose metabolism, whereas age and SAT were determinants of blood pressure parameters. CONCLUSIONS We suggest that visceral obesity is the best predictor of epicardial and pericardial fat in abdominally obese subjects. Myocardial TG content may present a separate entity that is influenced by factors beyond visceral adiposity.

Ectopic Fat Depots and Left Ventricular Function in Nondiabetic Men With Nonalcoholic Fatty Liver Disease

Background—Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Methods and Results—Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Conclusions—Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study.

Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease

Background  Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride‐rich lipoproteins (TRLs), RLPs, low‐density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD).

Epicardial Fat, Cardiac Dimensions, and Low-Grade Inflammation in Young Adult Monozygotic Twins Discordant for Obesity

Epicardial fat with its close proximity to coronary arteries has been suggested to be a significant predictor of cardiovascular disease. We studied the relations among acquired obesity, low-grade inflammation, and genetic factors in the accumulation of epicardial fat. A rare sample (n = 15) of healthy monozygotic (MZ) twin pairs discordant for obesity (intrapair difference in body mass index ≥3 kg/m(2)) and 9 concordant MZ pairs 23 to 33 years old were examined for cardiac structure, function, epicardial fat thickness (echocardiography), abdominal subcutaneous tissue, and visceral adipose tissue (VAT), liver fat (magnetic resonance imaging/spectroscopy), and serum high-sensitivity C-reactive protein. In the entire sample, MZ cotwins were remarkably similar in most echocardiographic measurements including epicardial fat (intraclass correlation 0.63, p = 0.0004). However, in the discordant pairs, the obese cotwins (16.5 kg, 23% heavier) had 26% more epicardial fat (p = 0.0029) than nonobese cotwins. They also had significantly larger atrial and left ventricular dimensions. Epicardial fat correlated with VAT (r = 0.49, p = 0.02) in individual twins and when using intrapair differences of measurements within pairs (r = 0.39, p = 0.06). In multiple regression analyses including abdominal subcutaneous tissue, VAT, and liver fat, high-sensitivity C-reactive protein was the only factor that remained significantly associated with epicardial fat in individual twins and within pairs. In conclusion, subjects who share the same genes seem to have similar cardiac dimensions. However, acquired obesity increases epicardial fat independent of genetic factors. The close relation between epicardial fat and low-grade inflammation is likely to contribute to the development of cardiovascular disease in obesity.

Multiple forms of sustained monomorphic ventricular tachycardia as common presentation in giant‐cell myocarditis

Idiopathic giant-cell myocarditis (IGCM) is a rare and highly malignant form of inflammatory heart disease of unknown origin. Pathognomonic histological features are the presence of multinucleated giant cells and a widespread lymphocytic inflammatory infiltration in association with myocyte necrosis.1 IGCM predominantly affects previously healthy young and middle-aged people. Association with autoimmune disorders has been described in 19% of cases.2 Clinically, IGCM often shows a rapid onset of symptoms followed by a fulminant course resulting in congestive heart failure, progressive heart block and ventricular arrhythmias. The response to treatment is poor, and affected patients are often referred to cardiac transplantation.2 Although IGCM is highly associated with ventricular tachycardia,3 the features of ventricular arrhythmias have not been dealt with. We characterise the type of ventricular tachycardias, the recognition of which might initiate measures to promptly diagnose and treat IGCM. Clinical, electrocardiographic, echocardiographic and histopathological data were extracted from the medical records of nine patients diagnosed with IGCM in Helsinki University Hospital, Helsinki, Finland, between 1991 and 2004. On the basis of electrocardiographic recordings and intracardiac electrophysiological studies, ventricular tachycardias were classified as monomorphic or polymorphic, and the morphological pattern of monomorphic ventricular tachycardia was categorised as right bundle branch block (RBBB) or left bundle branch block (LBBB), and superior or inferior axis in the frontal plane. In electrophysiological studies, programmed ventricular stimulation was carried out from …

Insulin resistance as predictor of the angiographic severity and extent of coronary artery disease.

Background. Insulin resistance (IR) is frequently observed in patients with coronary artery disease (CAD). Aim. To examine the association between IR and severity and extent of CAD. Methods. Quantitative coronary angiography (QCA) was used to assess coronary atherosclerosis in 107 patients with clinically suspected CAD. QCA‐derived indexes reflecting CAD severity, extent, and overall atheroma burden were calculated for the entire coronary tree, and separately for different coronary segments. IR was quantified using the homeostasis model assessment insulin resistance index (HOMA IR). Nondiabetic subjects (n = 83) were divided into group 1 (n = 41) with HOMA IR <1.8 (the median value), and group 2 (n = 42) with HOMA IR ⩾1.8. Group 3 comprised diabetic subjects (n = 24). Results. Global age‐ and gender‐adjusted indexes for severity (P = 0.007), extent (P = 0.038), and atheroma burden (P = 0.035) of CAD were higher in group 2 than in group 1. Similarly, the global severity (P = 0.027), extent (P = 0.090), and global atheroma burden (P = 0.024) indexes were higher in group 3 compared with group 1. IR was correlated with quantitative angiographic indexes for distal segments only, but not for proximal or mid segments of coronary vessels. Conclusions. Patients with more severe degree of IR have a more severe, extensive, and distal type of CAD than patients with lower degree of IR.

Cardiac steatosis in patients with dilated cardiomyopathy

Objective Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. Limited data exist on cardiac adiposity in subjects with dilated cardiomyopathy (DCM). The aim of the study was to examine the components of cardiac steatosis and their relationship to LV structure and function in non-diabetic DCM patients. Methods Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy (MRS), and LV function, visceral adipose (VAT) and abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MRI in 10 non-diabetic men with DCM and in 20 controls. Results In face of comparable intra-abdominal fat depots, myocardial TG [0.41% (0.21–2.19) vs 0.86% (0.31–2.24), p=0.038] was markedly lower and epicardial (895 mm2±110 vs 664 mm2±180, p=0.002) and pericardial fat [2173 mm2 (616–3673) vs 1168 mm2 (266–2319), p=0.039] depots were larger in patients with DCM compared with controls. In subjects with DCM, the LV global function index was decreased to a greater extent than the LV EF [21%±6 vs 34% (16–40)]. Conclusions Myocardial TG content decreased and epicardial and pericardial fat depots increased in non-diabetic subjects with DCM. Although recognised as a site of ectopic fat accumulation, the derangement of myocardial TG seems to play a specific role in the myocardial energy metabolism in congestive heart failure.

N-terminal Pro-brain Natriuretic Peptide, High-sensitivity Troponin and Pulmonary Artery Clot Score as Predictors of Right Ventricular Dysfunction in Echocardiography

BACKGROUND We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE). METHODS Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58±19 years) and without (n=31, age 55±16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission. RESULTS The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months. CONCLUSIONS Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD.

Diagnostic efficacy of myeloperoxidase to identify acute coronary syndrome in subjects with chest pain.

Abstract Background. Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task. Aims. To assess the role of novel biomarkers to identify ACS. Methods. Concentrations of lipids, lipoproteins, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), paraoxonase-1 (PON1), secretory phospholipase A2 (sPLA2), and myeloperoxidase (MPO) were measured in 703 patients (mean age 65.5 ± 11.2 years; 422 men, 281 women) without diabetes mellitus assigned to coronary angiogram. The subjects were divided into three groups: ACS (n = 242), stable angina pectoris (SAP) (n = 242), and normal coronary artery (NCA) (n = 219). Results. HDL-cholesterol (HDL-C) (P < 0.001) and apolipoproteinA-I concentrations (P < 0.0001) were lowest in subjects with ACS. LDL-C (P = 0.008) and non-HDL (P < 0.0001) were higher in the ACS group than in the SAP group. Leukocyte count (P < 0.0001), oxLDL (P < 0.05), hsCRP (P < 0.001), sPLA2 (P < 0.05), and MPO (P < 0.0001) were highest in the ACS group. In multivariate models, comprising all biomarkers, elevated level of MPO had the best discriminatory power to identify patients with ACS. Receiver-operating characteristic curve with and without MPO comparison differed significantly (P = 0.03 for both ACS versus NCA and ACS versus SAP). Conclusion. Our study shows that ACS associates with low HDL-C and biomarkers of oxidative stress and inflammation. The addition of MPO in biomarker panels might improve diagnostic accuracy for ACS.

Helical computerized tomography and NT-proBNP for screening of right ventricular overload on admission and at long term follow-up of acute pulmonary embolism

BackgroundRight ventricular dysfunction (RVD) in acute pulmonary embolism (APE) can be assessed with helical computerized tomography (CT) and transthoracic echocardiography (TTE). Signs of RVD and elevated natriuretic peptides like NT-proBNP and cardiac troponin (TnT) are associated with increased risk of mortality. However, the prognostic role of both initial diagnostic strategy and the use of NT-proBNP and TnT for screening for long-term probability of RVD remains unknown. The aim of the study was to determine the role of helical CT and NT-proBNP in detection of RVD in the acute phase. In addition, the value of NT-proBNP for ruling out RVD at long-term follow-up was assessed.MethodsSixty-three non-high risk APE patients were studied. RVD was assessed at admission in the emergency department by CT and TTE, and both NT-proBNP and TnT samples were taken. These, excepting CT, were repeated seven months later.ResultsAt admission RVD was detected by CT in 37 (59 %) patients. RVD in CT correlated strongly with RVD in TTE (p < 0.0001). NT-proBNP was elevated (≥ 350 ng/l) in 32 (86 %) patients with RVD but in only seven (27 %) patients without RVD (p < 0.0001). All the patients survived until the 7-month follow-up. TTE showed persistent RVD in 6 of 63 (10 %) patients who all had RVD in CT at admission. All of them had elevated NT-proBNP levels in the follow-up compared with 5 (9 %) of patients without RVD (p < 0.0001).ConclusionsTTE does not confer further benefit when helical CT is used for screening for RVD in non-high risk APE. All the patients who were found to have RVD in TTE at seven months follow-up had had RVD in the acute phase CT as well. Thus, patients without RVD in diagnostic CT do not seem to require further routine follow-up to screen for RVD later. On the other hand, persistent RVD and thus need for TTE control can be ruled out by assessment of NT-proBNP at follow-up. A follow-up protocol based on these findings is suggested.