Nonalcoholic Fatty Liver Disease Incidence and Remission and Their Predictors During 7 Years of Follow-up Among Finns.

CONTEXT: The incidence and remission of nonalcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia. OBJECTIVE: This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population. METHODS: The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with a 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available. RESULTS: At baseline, 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07; 95% CI, 1.02-1.13; P = .009), waist circumference (WC) (2.77, 1.91-4.01 per 1 SD; P < .001), and triglycerides (2.31, 1.53-3.51 per 1 SD; P < .001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per 1 SD; P = .006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per 1 SD; P < .001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per 1 SD; P = .007) and WC change (0.38, 0.25-0.59 per 1 SD; P < .001). CONCLUSION: During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.

Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood: the cardiovascular risk in young Finns study.

PURPOSE: There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. MATERIALS AND METHODS: Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3-18 years, females 54.3%) who had risk factor and lifestyle data available since childhood. Systemic hemodynamics were measured in 2007 (aged 30-45 years) by whole-body impedance cardiography. RESULTS: In the multivariable regression analysis, independent predictors of the adulthood SVRI were childhood BMI, blood glucose, vegetable consumption, smoking, and physical activity (p ≤ .046 for all). Vegetable consumption, smoking, and physical activity remained significant when adjusted for corresponding adult data (p ≤ .036 for all). For the CI, independent predictors in childhood were BMI, systolic blood pressure, vegetable consumption, and physical activity (p ≤ .044 for all), and the findings remained significant after adjusting for corresponding adult data (p ≤ .046 for all). The number of childhood and adulthood risk factors and unfavourable lifestyle factors was directly associated with the SVRI (p < .001) in adulthood. A reduction in the number of risk factors and unfavourable lifestyle factors or a favourable change in BMI status from childhood to adulthood was associated with a lower SVRI in adulthood (p < .001). CONCLUSION: Childhood BMI, blood glucose, vegetable consumption, smoking and physical activity independently predict systemic vascular resistance in adulthood. A favourable change in the number of risk factors or BMI from childhood to adulthood was associated with lower vascular resistance in adulthood.

Association of lifetime blood pressure with adulthood exercise blood pressure response: the cardiovascular risk in young Finns study.

PURPOSE: Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. MATERIALS AND METHODS: This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6-18 years; follow-up in adulthood in 27-29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while in adulthood BP was considered elevated if systolic BP was ≥120 mmHg or diastolic BP was ≥80 mmHg or if use of antihypertensive medications was self-reported. A maximal cardiopulmonary exercise test with BP measurements was performed by participants in 2008-2009, and exercise BP was considered exaggerated (EEBP) if peak systolic blood pressure exceeded 210 mmHg in men and 190 mmHg in women. RESULTS: Participants with consistently high BP from childhood to adulthood and individuals with normal childhood but high adulthood BP had an increased risk of EEBP response in adulthood (relative risk [95% confidence interval], 3.32 [2.05-5.40] and 3.03 [1.77-5.17], respectively) in comparison with individuals with normal BP both in childhood and adulthood. Interestingly, individuals with elevated BP in childhood but not in adulthood also had an increased risk of EEBP [relative risk [95% confidence interval], 2.17 [1.35-3.50]). CONCLUSIONS: These findings reinforce the importance of achieving and sustaining normal blood pressure from childhood through adulthood.

FDG-PET in possible cardiac sarcoidosis: Right ventricular uptake and high total cardiac metabolic activity predict cardiovascular events.

BACKGROUND: Cardiac involvement accounts for the majority of morbidity and mortality in sarcoidosis. Pathological myocardial fluorodeoxyglucose (FDG)-uptake in positron emission tomography (PET) has been associated with cardiovascular events and quantitative metabolic parameters have been shown to add prognostic value. Our aim was to study whether the pattern of pathological cardiac FDG-uptake and quantitative parameters are able to predict cardiovascular events in patients with suspected cardiac sarcoidosis (CS). METHODS: 137 FDG-PET examinations performed in Tampere University Hospital were retrospectively analyzed visually and quantitatively. Location of pathological uptake was noted and pathological metabolic volume, average standardized uptake value (SUV), and total cardiac metabolic activity (tCMA) were calculated. Patients were followed for ventricular tachycardia, decrease in left ventricular ejection fraction, and death. RESULTS: Eleven patients had one or more cardiovascular events during the follow-up. Five patients out of 12 with uptake in both ventricles had an event during follow-up. Eight patients had high tCMA (> 900 MBq) and three of them had a cardiovascular event. Right ventricular uptake and tCMA were significantly associated with cardiovascular events during follow-up (P-value .001 and .018, respectively). CONCLUSIONS: High tCMA and right ventricular uptake were significant risk markers for cardiac events among patient with suspected CS.

Systemic vascular resistance predicts the development of hypertension: the cardiovascular risk in young Finns study.

PURPOSE: To study whether systemic hemodynamics, especially systemic vascular resistance, predicts the development of hypertension and improves the risk prediction of incident hypertension beyond common risk factors in the risk models in young adults. MATERIALS AND METHODS: Typical risk factors for hypertension in the risk prediction models (systolic and diastolic blood pressure, parental history of hypertension, age, sex, body-mass index, smoking), laboratory values (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, C-reactive protein), heart rate (HR), stroke index (SI), and systemic vascular resistance index (SVRI) calculated by whole-body impedance cardiography were evaluated in 2007 and blood pressure in 2011 in 1293 Finnish adults (aged 30-45 years; females 56%; n = 1058 normotensive in 2007). RESULTS: Of hemodynamic variables, SVRI and HR evaluated in 2007 were independently associated with systolic blood pressure (p < 0.001 and p = 0.047, respectively) and SVRI with diastolic blood pressure measured in 2011 (p = 0.014), and SVRI and HR were independent predictors of incident hypertension (p < 0.001 and p = 0.024, respectively). SVRI was the most significant predictor of incident hypertension independently of other risk factors (odds ratio 2.73 per 1 standard deviation increase, 95% confidence interval 1.93-3.94, p < 0.001). The extended prediction model (including SVRI) improved the incident hypertension risk prediction beyond other risk factors, with an area under the receiver operating characteristic curve of 0.846 versus 0.817 (p = 0.042) and a continuous net reclassification improvement of 0.734 (p < 0.001). CONCLUSIONS: These findings suggest that systemic vascular resistance index predicts the incidence of hypertension in young adults and that the evaluation of systemic hemodynamics could provide an additional tool for hypertension risk prediction.

Pulse wave velocity is related to exercise blood pressure response in young adults. The Cardiovascular Risk in Young Finns Study.

Purpose: High pulse wave velocity (PWV), a marker of increased arterial stiffness, and an exaggerated exercise blood pressure (EEBP) response during an exercise test have both been related to an increased risk of hypertension and cardiovascular events. Contradictory results have been published about the association between these two parameters, and their relation in healthy young adults is unknown.Materials and methods: This study consisted of 209 young adults (mean age 38 years) who participated in the ongoing Cardiovascular Risk in Young Finns Study between 2007 and 2009. We measured resting PWV with impedance cardiography in 2007, and participants performed a maximal cardiopulmonary exercise test with blood pressure (BP) measurements at rest, during exercise and during recovery in 2008-2009.Results: High PWV (≥age- and sex-specific median) at baseline was associated with EEBP (SBP >210 mmHg for men and >190 mmHg for women) an average of 14 months later and with systolic BP during different stages of exercise from rest to peak and recovery (during peak exercise, ß ± SE was 4.1 ± 1.1, p < 0.001). The association between high PWV and systolic BP remained after adjustment for traditional cardiovascular risk factors and other exercise parameters (during peak exercise, ß ± SE was 2.3 ± 1.1, p = 0.04).Conclusions: Increased arterial stiffness predicts EEBP during a maximal exercise test in young adults during all stages of exercise from rest to peak and recovery. PWV could provide an additional tool for EEBP risk evaluation.

18-FDG-PET in a patient cohort suspected for cardiac sarcoidosis: Right ventricular uptake is associated with pathological uptake in mediastinal lymph nodes.

INTRODUCTION: In up to 65% of cardiac sarcoidosis patients, the disease is confined to the heart. Diagnosing isolated cardiac sarcoidosis is challenging due to the low sensitivity of endomyocardial biopsy. If cardiac sarcoidosis is part of biopsy-confirmed systemic sarcoidosis, the diagnosis can be based on cardiac imaging studies. We compared the imaging features of patients with isolated cardiac FDG uptake on positron emission tomography with those who had findings indicative of systemic sarcoidosis. MATERIALS AND METHODS: 137 consecutive cardiac FDG-PET/CT studies performed on subjects suspected of having cardiac sarcoidosis were retrospectively analyzed. RESULTS: 33 patients had pathological left ventricular FDG uptake, and 12 of these also had pathological right ventricular uptake. 16/33 patients with pathological cardiac uptake had pathological extracardiac uptake. 10/12 patients with both LV- and RV-uptake patterns had extracardiac uptake compared to 6/21 of those with pathological LV uptake without RV uptake. SUVmax values in the myocardium were higher among patients with abnormal extracardiac uptake. The presence of extracardiac uptake was the only imaging-related factor that could predict a biopsy indicative of sarcoidosis. CONCLUSION: Right ventricular involvement seems to be more common in patients who also have findings suggestive of suspected systemic sarcoidosis, compared with patients with PET findings indicative of isolated cardiac disease.

Combination of low blood pressure response, low exercise capacity and slow heart rate recovery during an exercise test significantly increases mortality risk.

Aims: We investigated the combination of low systolic blood pressure (SBP) response, low exercise capacity (EC) and slow heart rate recovery (HRR) during an exercise test in mortality prediction.Patients and methods: Our population consisted of 3456 patients from the Finnish Cardiovascular Study. A failure of SBP to increase >42 mmHg was defined as a low response. Low EC was defined as < 8 metabolic equivalents. 1-minute HRR ≤18 bpm from maximum was defined as slow HRR.Results: During a median follow up of 10.0 years, 537 participants died. Reduced SBP response, low EC and slow HRR were independent predictors of all-cause and CV mortality (p < .001 for all). Patients with reduced SBP response, low EC and slow HRR had a very high mortality rate of 42.1% during follow up compared to only 4.5% of the patients without any of these risk factors. The hazard ratios for all-cause mortality in patients with one, two or three of the studied risk factors were 3.2, 6.0, and 10.6, respectively (p < .001 for all).Conclusion: The combination of reduced SBP response, low exercise capacity, and reduced HRR in an exercise test is associated with very high mortality and can be used in risk stratification.Key messagesThe combination of low blood pressure response, low exercise capacity and slow heart rate recovery in an exercise test is able to identify a group of patients in a very high mortality risk.These parameters are easily derived from an exercise test.All parameters are commonly available in clinical practice.

18F-FDG-PET in Finnish patients with clinical suspicion of cardiac sarcoidosis: Female sex and history of atrioventricular block increase the prevalence of positive PET findings.

INTRODUCTION: Fluorodeoxyglucose positron emission tomography (FDG-PET) is a non-invasive imaging modality that has been shown to be a feasible method to demonstrate myocardial inflammation. The aim of this study was to identify the patients suspected of having cardiac sarcoidosis (CS), who are most likely to benefit from PET imaging. MATERIALS AND METHODS: 137 patients suspected of having CS underwent a dedicated cardiac FDG-PET examination at Tampere University Hospital between August 2012 and September 2015. These examinations were retrospectively analyzed. RESULTS: 33 and 12 of the 137 patients had abnormal left and right ventricular (LV and RV) FDG-uptake, respectively. Abnormal LV-uptake and RV-uptake were significantly associated with female sex and a history of advanced AV-block (P < 0.05). Abnormal RV-uptake was also associated with ventricular tachycardia and atrial fibrillation (P < 0.05). 56% of the 27 female patients with a history of AV-block had a pathological PET finding compared to only 6% of the 49 male patients without a history of AV-block. There were 17 female patients with history of both AV-block and ventricular tachycardia, 71% of them had abnormal PET finding. CONCLUSIONS: Abnormal FDG-PET findings were associated with female sex, AV-block, and arrhythmias in this clinical cohort.

Novel ECG parameters are strongly associated with inflammatory 18F-FDG PET findings in patients with suspected cardiac sarcoidosis.

BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a feasible method to investigate the inflammatory activity of the myocardium in cardiac sarcoidosis. However, PET is costly and not as widely available as standard electrocardiogram (ECG). Current ECG findings related to cardiac sarcoidosis are highly non-specific. In this study, our aim was to determine whether novel ECG parameters are associated with pathological PET findings in patients with suspected cardiac sarcoidosis. METHODS: A total of 133 patients underwent cardiac FDG PET examination in Tampere University Hospital between August 2012 and September 2015. The left ventricular FDG uptake was categorized as either normal or pathological. Additionally, in-depth analyses of resting ECG were performed. Among other parameters, the presence of septal and inferolateral remodelling was assessed. These are novel ECG parameters related to local structural changes in the myocardium. RESULTS: In the ECG, septal and inferolateral remodelling, as well as widespread QRS fragmentation were significantly associated with pathological left ventricular FDG uptake even if adjusted for age, sex, body mass index, underlying cardiovascular disease and cardiac medication (p<0.05 for all). When all these ECG parameters were combined in a logistic regression model, only septal remodelling remained independently associated with abnormal left ventricular uptake (p<0.05). CONCLUSIONS: Our findings show that novel ECG parameters septal and inferolateral remodelling, as well as diffuse QRS fragmentation, are strongly associated with pathological cardiac findings in FDG PET. Thus, the presence of these ECG findings may warrant the clinician to consider the possibility of cardiac sarcoidosis.

Heart rate variability is independently associated with C-reactive protein but not with Serum amyloid A. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Increased levels of C-reactive protein (CRP) and serum amyloid A (SAA) are associated with an increased risk of cardiovascular disease. It is hypothesized that dysregulation of the autonomic nervous system (ANS) leads to increased inflammation via the cholinergic anti-inflammatory pathway. Heart rate variability (HRV) is a marker of ANS function. HRV has been shown to be associated with CRP levels. Currently, there are no studies addressing the relationship between HRV and SAA. DESIGN: The purpose of this study was to compare the associations between HRV, CRP and SAA in healthy young adults. CRP and SAA concentrations and short-term HRV indices [high frequency (HF), low frequency (LF), total spectral component of HRV, root mean square differences of successive R-R intervals, the standard deviation of all R-R intervals and ratio between LF and HF) were measured in 1601 men and women aged 24-39 taking part in the Cardiovascular Risk in Young Finns study. RESULTS: A significant inverse correlation (P < 0·05) between HRV indices and inflammatory markers was observed. However, in linear regression analyses, only inverse association between HRV indices and CRP levels remained significant (P < 0·05), while association between HRV indices and SAA levels was attenuated to the null (P > 0·05) after adjusting for age, sex, body mass index, cholesterol levels, leptin and other common traditional cardiovascular risk factors. CONCLUSIONS: Reduced HRV indices are independently associated with increased CRP levels, but not with SAA levels. This association supports the hypothesis that dysregulation of the ANS may lead to increased inflammation early in adulthood.

Use of combined oral contraceptives alters metabolic determinants and genetic regulation of C-reactive protein. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Use of combined oral contraceptives (COCs) is known to increase concentrations of C-reactive protein (CRP), an important predictor of cardiovascular disease. The inflammatory nature of the disease is well acknowledged. The aim of this study was to find out whether the metabolic, lifestyle and genetic determinants of CRP differ between women who use COCs and those who do not use any hormonal contraceptives (non-users). MATERIAL AND METHODS: A total of 1,257 women (24-39 years) participated in the ongoing Cardiovascular Risk in Young Finns Study, a population based cross-sectional follow-up study. Use of hormonal contraceptives was determined by questionnaire. Plasma CRP and other cardiovascular risk factors were measured; five CRP gene polymorphisms were genotyped (-717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A) and CRP haplotypes were constructed. RESULTS: Multivariate regression analysis revealed that BMI and leptin were the main determinants of CRP in non-users, whereas in COC users the main determinants were BMI, leptin and triglycerides. The median CRP and triglyceride values were significantly higher in COC users than in non-users. The correlations between triglyceride and CRP were tested separately in different COC users in accordance with progestagen content and dosage, the analysis revealing significant association only in women using a high dosage of progestagen or cyproterone. The haplotypes of CRP gene had no significant association with CRP concentration in COC users, while independent effects on CRP were found in non-users. CONCLUSION: Our study suggests that use of COCs alters the metabolic determinants and genetic regulation of CRP.