Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome.

Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-ß1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.

Observed changes in cardiovascular risk factors among high-risk middle-aged men who received lifestyle counselling: a 5-year follow-up.

OBJECTIVE: To examine the long-term impact of health counselling among middle-aged men at high risk of CVD. DESIGN: An observational study with a 5-year follow-up. SETTING AND INTERVENTION: All men aged 40 years in Helsinki have been invited to a visit to evaluate CVD risk from 2006 onwards. A modified version of the North Karelia project risk tool (CVD risk score) served to assess the risk. High-risk men received lifestyle counselling based on their individual risk profile in 2006 and were invited to a follow-up visit in 2011. SUBJECTS: Of the 389 originally high-risk men, 159 participated in the follow-up visits in 2011. Based on their follow-up in relation the further risk communication, we divided the participants into three groups: primary health care, occupational health care and no control visits. MAIN OUTCOME MEASURES: Lifestyle and CVD risk score change. RESULTS: All groups showed improvements in lifestyles. The CVD risk score decreased the most in the group that continued the risk communication visits in their primary health care centre (6.1 to 4.8 [95% CI -1.6 to -0.6]) compared to those who continued risk communication visits in their occupational health care (6.0 to 5.4 [95% CI -1.3 to 0.3]), and to those with no risk communication visits (6.0 to 5.9 [95% CI -0.5 to 0.4]). CONCLUSIONS: These findings indicate that individualized lifestyle counselling improves health behaviour and reduces total CVD risk among middle-aged men at high risk of CVD. Sustained improvement in risk factor status requires ongoing risk communication with health care providers. KEY POINTS Studies of short duration have shown that lifestyle changes reduce the risk of cardiovascular disease among high-risk individuals. Sustaining these lifestyle changes and maintaining the lower disease risk attained can prove challenging. Cardiovascular disease (CVD) risk assessment and individualized health counselling for high-risk men, when implemented in primary health care, have the potential to initiate lifestyle changes that support risk reduction. Attaining a sustainable reduction in CVD risk requires a willingness to engage in risk-related communication from both health care providers and the individual at high risk.

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.

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.

[Prevention of arterial diseases in the 2010s: the European treatment guideline]. / Valtimosairauksien ehkäisy 2010-luvulla: eurooppalainen hoitosuositus.

Reduction of risk factors at the population level forms the basis of the European recommendation of 2012 for the prevention of arterial diseases. Actions at the individual level arise from risk assessment. The risk of arterial disease is graded into four categories, the uppermost ones comprising patients who have already developed the disease, diabetics, those suffering from renal insufficiency and those carrying a serious gene defect. In Finland the risk among healthy people is assessed by using the FINRISKI tool. Non-smoking, healthy diet and regular exercise are suitable for all. Statins are an effective and safe means of prevention for those at high risk regardless of lipid values.

Impact of health counselling on cardiovascular disease risk in middle aged men: influence of socioeconomic status.

BACKGROUND: The inverse association between socioeconomic status and cardiovascular disease is well documented. We examined whether the impact of health counselling on cardiovascular risk factors in middle-aged men differed according to socioeconomic status. METHODS: We used data from a community based study assessing the risk for cardiovascular disease among middle-aged men in Helsinki, Finland. Traditional cardiovascular disease risk factors were measured and cardiovascular disease risk was assessed by a modified risk tool used in the North Karelia project (CVD Risk Score). Those men with increased risk for cardiovascular disease at their baseline visit in 2006 received lifestyle counselling. After two years these high-risk men were invited to a follow-up visit. The same measurements and risk assessments were repeated. RESULTS: Based on the CVD Risk Score there were significant differences between the groups at baseline (p = 0.001) and at follow-up (p<0.001) with the highest scores in the lowest educational group. There were no significant differences in traditional cardiovascular risk factors according to educational attainment between groups either at baseline or at follow-up. Baseline lifestyle characteristics differed between the groups regarding use of soft fat (p = 0.019). All groups responded positively to lifestyle counselling. CONCLUSIONS: The present study showed that lifestyle counselling is feasible in high-risk middle-aged men and lifestyle intervention works in all educational groups. Interestingly the traditional risk factors did not show improvement, but the risk score improved. From a practical point of view our findings stress the importance of using risk score calculators in health counselling instead of looking at individual cardiovascular disease risk factors.

Cardiac steatosis and left ventricular function in men with metabolic syndrome.

BACKGROUND: Ectopic accumulation of fat accompanies visceral obesity with detrimental effects. Lipid oversupply to cardiomyocytes leads to cardiac steatosis, and in animal studies lipotoxicity has been associated with impaired left ventricular (LV) function. In humans, studies have yielded inconclusive results. The aim of the study was to evaluate the role of epicardial, pericardial and myocardial fat depots on LV structure and function in male subjects with metabolic syndrome (MetS). METHODS: A study population of 37 men with MetS and 38 men without MetS underwent cardiovascular magnetic resonance and proton magnetic spectroscopy at 1.5 T to assess LV function, epicardial and pericardial fat area and myocardial triglyceride (TG) content. RESULTS: All three fat deposits were greater in the MetS than in the control group (p <0.001). LV diastolic dysfunction was associated with MetS as measured by absolute (471 mL/s vs. 667 mL/s, p = 0.002) and normalized (3.37 s⁻¹ vs. 3.75 s⁻¹, p = 0.02) LV early diastolic peak filling rate and the ratio of early diastole (68% vs. 78%, p = 0.001). The amount of epicardial and pericardial fat correlated inversely with LV diastolic function. However, myocardial TG content was not independently associated with LV diastolic dysfunction. CONCLUSIONS: In MetS, accumulation of epicardial and pericardial fat is linked to the severity of structural and functional alterations of the heart. The role of increased intramyocardial TG in MetS is more complex and merits further study.

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.

Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease.

BACKGROUND: Abdominal obesity is a more important risk factor than overall obesity in predicting the development of type 2 diabetes and cardiovascular disease. From a preventive and public health point of view it is crucial that risk factors are identified at an early stage, in order to change and modify behaviour and lifestyle in high risk individuals. METHODS: Data from a community based study was used to assess the risk for type 2 diabetes, cardiovascular disease and prevalence of metabolic syndrome in middle-aged men. In order to identify those with increased risk for type 2 diabetes and/or cardiovascular disease sensitivity and specificity analysis were performed, including calculation of positive and negative predictive values, and corresponding 95% CI for eleven different cut-off points, with 1 cm intervals (92 to 102 cm), for waist circumference. RESULTS: A waist circumference ≥94 cm in middle-aged men, identified those with increased risk for type 2 diabetes and/or for cardiovascular disease with a sensitivity of 84.4% (95% CI 76.4% to 90.0%), and a specificity of 78.2% (95% CI 68.4% to 85.5%). The positive predictive value was 82.9% (95% CI 74.8% to 88.8%), and negative predictive value 80.0%, respectively (95% CI 70.3% to 87.1%). CONCLUSIONS: Measurement of waist circumference in middle-aged men is a reliable test to identify individuals at increased risk for type 2 diabetes and cardiovascular disease. This measurement should be used more frequently in daily practice in primary care in order to identify individuals at risk and when planning health counselling and interventions.