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The specialty of clinical physiology was established in Finland about 20 years later than in Sweden. In the early 1960s, six physicians working mainly in preclinical departments of physiology were certified as specialists in clinical physiology. Many of the first specialists working in hospitals received specialist training in Sweden. The first hospital laboratories of clinical physiology were established in Tampere Central Hospital and Turku University Hospital in 1968. Thereafter, laboratories of clinical physiology were also established in Helsinki University Hospital and in Kuopio University Hospital and later also in most central hospitals. After clinical physiology laboratories were set up in hospitals and the number of specialists increased, the specialty gradually had more impact in clinical work. In the 1999 reform, nuclear medicine, which had previously been a subspecialty, was combined with clinical physiology. Arto Uusitalo was nominated the first professor of clinical physiology in Tampere University in 1984. The first professor in Helsinki University was Anssi Sovijärvi (1994), in Kuopio University Esko Länsimies (1998), and in Turku University Jaakko Hartiala (2003). Today, at four universities professors of clinical physiology and nuclear medicine lead research and medical education in this specialty. The hospital laboratories have modern equipment, which promotes multidisciplinary research with clinicians in fruitful collaboration. The Finnish Society of Clinical Physiology was founded in 1975. Today, it has about 160 members, about half of whom are specialists in the field. On its 40th anniversary, the Society decided to publish the history of clinical physiology in Finland.

Purpose To study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol. Methods Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test. Results During the stimulation protocol, leptin concentrations elevated (P P = 0.03), while estradiol levels increased (P P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased. Conclusion No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

Aims Most international guidelines recommend that repeat blood pressure (BP) readings are required for BP classification. Two international guidelines diverge from this by recommending that no further BP measurements are required if the first clinic BP is below a hypertension threshold. The extent to which within-visit BP variability patterns change over time, and whether this could impact BP classification is unknown. We sought to examine this. Methods and results Data were from the Cardiovascular Risk in Young Finns Study, a prospective cohort study. Up to 2799 participants were followed from childhood (9–15 years) to adulthood (18–49 years) over up to six visits. Patterns of within-visit systolic BP (SBP) variability were defined as no-change, decrease, increase between consecutive readings (with 5 mmHg change thresholds). Classification of SBP (normal, high-normal, hypertension) using the first reading was compared with repeat readings. On average, SBP decreased with subsequent measures, but with major individual variability (no-change: 56.9–62.7%; decrease: 24.1–31.6%; increase: 11.5–16.8%). Patterns of SBP variability were broadly similar from childhood to adulthood, with the highest prevalence of an increase among participants categorized with normal SBP (12.6–20.3%). The highest prevalence of SBP reclassification occurred among participants with hypertension (28.9–45.3% reclassified as normal or high-normal). The prevalence of reclassification increased with the magnitude of change between readings. Conclusion There is a major individual variation of within-visit SBP change in childhood and adulthood and can influence BP classification. This highlights the importance of consistency among guidelines recommending that repeat BP measurements are needed for BP classification.

BACKGROUND AND AIMS Our objective was to study relationships between the new biomarker of vascular health, carotid artery longitudinal wall motion (CALM) and metabolic syndrome (MetS). METHODS Carotid ultrasound and assessment of MetS and its components were performed with 281 subjects aged 30-45 years. In the longitudinal motion analysis, the amplitude of motion and the antegrade-oriented and retrograde-oriented components of motion between the intima-media complex and adventitial layer of the common carotid artery wall were assessed. RESULTS Metabolic syndrome, according to the harmonized criteria, was detected in 53 subjects (19%). MetS was significantly associated with increased antegrade and decreased retrograde longitudinal motion in the carotid artery wall. Augmented antegrade amplitude of longitudinal motion was associated with obesity (β = 0.149, p

Background Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. Methods We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population (N = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve. Results After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p 25 kg/m(2)) associated with 4.7% (2.5-6.9%, p 30kg/m(2)) resulted in a 21% (17.3-32.9%, p

International audience; Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

Aims The aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). Methods Medical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. Results Prevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. Conclusions Almost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Chronic oral infection/inflammation is cross-sectionally associated with metabolic syndrome (MetS) in adults, but there are few longitudinal studies and studies on childhood oral infections and adult MetS risk. We investigated whether childhood clinical parameters indicative of oral infection/inflammation were associated with adulthood MetS and its components. A total of 755 children aged 6, 9, and 12 y underwent a clinical oral examination in 1980 as part of the Cardiovascular Risk in Young Finns Study. Oral health measures included bleeding on probing (BOP), periodontal probing pocket depth, caries, fillings, and visible plaque. Metabolic parameters were determined at baseline and during follow-up. MetS was diagnosed ( n = 588, 77.9%) in the adulthood at 21 y (in 2001), 27 y (in 2007), and 31 y (in 2011) after the oral assessment, when the participants were 27 to 43 y old. Regression analyses were adjusted for childhood age, sex, body mass index, and family income, as well as adulthood smoking and education level. In adulthood, MetS was diagnosed in 11.9% (2001), 18.7% (2007), and 20.7% (2011) of participants at the 3 follow-ups. Childhood caries and fillings were associated with increased risk of adult MetS (risk ratio [95% CI], 1.25 [0.90 to 2.45] and 1.27 [1.02 to 1.99]) and with increased systolic blood pressure (1.78 [1.01 to 4.26] and 2.48 [1.11 to 4.12]) and waist circumference (2.25 [1.02 to 4.99] and 1.56 [1.01 to 3.25]), whereas BOP and visible plaque were associated with plasma glucose (1.97 [1.08 to 3.60] and 1.88 [1.00 to 3.53]). Severity of BOP ( P = 0.015) and caries ( P = 0.005) and teeth with plaque ( P = 0.027) were associated with number of MetS components. No such trends were seen with probing pocket depth. Childhood oral infection/inflammation was associated with adverse metabolic parameters and MetS in adulthood.

We studied whether exposure to parental smoking in childhood/adolescence is associated with midlife cognitive function, leveraging data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3–18 years was followed between 1980 and 2011. In 2011, cognitive testing was performed on 2,026 participants aged 34–49 years using computerized testing. Measures of secondhand smoke exposure in childhood/adolescence consisted of parental self-reports of smoking and participants’ serum cotinine levels. Participants were classified into 3 exposure groups: 1) no exposure (nonsmoking parents, cotinine

Background: Do different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol? Does the IVF stimulation induce metabolic changes, which might impact maternal health? Methods: Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs) three days before each visit. In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test, in which the blood samples were taken at five time points at every three visits. They also filled visual analog scales to exhibit satiety and appetite. Twenty-eight of the subjects had only fasting blood samples. Results: During the stimulation protocol, leptin concentrations elevated (P Conclusions: No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, no harmful metabolic effects occurred, which might have a disproportionate impact on maternal health. Trial registration: Not applicable. This study is a clinical study without intervention.

Introduction: The role of risk factor profile in childhood and adolescence on adulthood cognitive function and whether it differs by genetic risk is still obscure. To bring this evidence, we determined cognitive domain-specific youth risk factor profiles leveraging the childhood/adolescence data from the Cardiovascular Risk in Young Finns Study and examined whether genetic propensity for poor cognitive function modifies the association between the risk profiles and adulthood cognitive function. Methods: From 1980, a population-based cohort of 3,596 children (age 3–18 years) has been repeatedly followed up for 31 years. Computerized cognitive test measuring (1) memory and learning, (2) short-term working memory, (3) reaction time, and (4) information processing was performed for 2,026 participants (age 34–49 years). Cognitive domain-specific youth risk profile scores, including physical and environmental factors, were assessed from the data collected at baseline and categorized into favourable, intermediate, and unfavourable. A polygenic risk score for a poor cognitive function was categorized into low, intermediate, and high risk. Results: At all genetic risk levels, a favourable youth risk factor profile is associated with better learning and memory, short-term working memory, and information processing compared to unfavourable risk profile (e.g., β = 0.501 SD, 95% CI: 0.043–0.959 for memory and learning among participants with high genetic risk). However, no significant interactions were observed between the youth risk factor profile score and genetic propensity for any cognitive domain (p > 0.299 for all). Conclusion: A favourable youth risk factor profile may be beneficial for cognitive function in adulthood, irrespective of genetic propensity for poor cognitive function.

Publisher Copyright: © 2021 The Author(s) We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.

Background Atrial fibrillation (AF) is the most common tachyarrhythmia and associated with a risk of stroke. The detection and diagnosis of AF represent a major clinical challenge due to AF’s asymptomatic and intermittent nature. Novel consumer-grade mobile health (mHealth) products with automatic arrhythmia detection could be an option for long-term electrocardiogram (ECG)-based rhythm monitoring and AF detection. Objective We evaluated the feasibility and accuracy of a wearable automated mHealth arrhythmia monitoring system, including a consumer-grade, single-lead heart rate belt ECG device (heart belt), a mobile phone application, and a cloud service with an artificial intelligence (AI) arrhythmia detection algorithm for AF detection. The specific aim of this proof-of-concept study was to test the feasibility of the entire sequence of operations from ECG recording to AI arrhythmia analysis and ultimately to final AF detection. Methods Patients (n=159) with an AF (n=73) or sinus rhythm (n=86) were recruited from the emergency department. A single-lead heart belt ECG was recorded for 24 hours. Simultaneously registered 3-lead ECGs (Holter) served as the gold standard for the final rhythm diagnostics and as a reference device in a user experience survey with patients over 65 years of age (high-risk group). Results The heart belt provided a high-quality ECG recording for visual interpretation resulting in 100% accuracy, sensitivity, and specificity of AF detection. The accuracy of AF detection with the automatic AI arrhythmia detection from the heart belt ECG recording was also high (97.5%), and the sensitivity and specificity were 100% and 95.4%, respectively. The correlation between the automatic estimated AF burden and the true AF burden from Holter recording was >0.99 with a mean burden error of 0.05 (SD 0.26) hours. The heart belt demonstrated good user experience and did not significantly interfere with the patient’s daily activities. The patients preferred the heart belt over Holter ECG for rhythm monitoring (85/110, 77% heart belt vs 77/109, 71% Holter, P=.049). Conclusions A consumer-grade, single-lead ECG heart belt provided good-quality ECG for rhythm diagnosis. The mHealth arrhythmia monitoring system, consisting of heart-belt ECG, a mobile phone application, and an automated AF detection achieved AF detection with high accuracy, sensitivity, and specificity. In addition, the mHealth arrhythmia monitoring system showed good user experience. Trial Registration ClinicalTrials.gov NCT03507335; https://clinicaltrials.gov/ct2/show/NCT03507335

Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3-18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m2, 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m2, 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m2, 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention. publishedVersion

Background: Within-visit SBP variability is associated with age and SBP, but its long-term clinical significance is unknown. We examined the association between child, adult, and life-time within-visit SBP variability with markers of end-organ damage using data from a 31-year longitudinal study. Methods: Within-visit SBP variability was calculated as the standard deviation of three sitting SBP readings among up to 3010 participants aged 6–18 years (childhood) who were re-measured up to seven times to mid-adulthood. Markers of cardiovascular end-organ damage in adulthood were carotid intima--media thickness, brachial flow-mediated dilatation, carotid distensibility, pulse wave velocity, left ventricular mass index, carotid plaque, and coronary artery calcification. Results: The mean (standard deviation) cumulative within-visit SBP variability was 2.7 (1.5) mmHg in childhood, 3.9 (1.9) mmHg in adulthood and 3.7 (1.5) mmHg across the observed life-time. Childhood within-visit SBP variability was not correlated with its subsequent values measured from 3 to 31 years later. With adjustment for age, sex, cumulative SBP, BMI and serum lipids, neither child, adult, or life-time cumulative within-visit SBP variability associated with markers of cardiovascular end-organ damage. However, higher child, adult, and life-time cumulative SBP significantly associated with higher carotid intima--media thickness, higher pulse wave velocity, lower brachial flow-mediated dilatation, lower carotid distensibility in adulthood. Conclusion: Within-visit SBP variability from childhood to adulthood does not provide additional predictive utility over SBP over the same period of the life course.

Background and aims Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. Methods The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3–18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6–18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. Results Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen >50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76–5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99–2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26–2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. Conclusions Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

BACKGROUND Associations of cardiometabolic risk factors with heart rate variability (HRV) in children are unclear. We examined associations of cardiometabolic risk score (CRS) and individual cardiometabolic risk factors with HRV variables in 6- to 8-year-olds. METHODS The participants were a population-based sample of 443 children participating in baseline measurements of the Physical Activity and Nutrition in Children trial. Cardiometabolic risk factors included waist circumference (WC), insulin, glucose, triglycerides, HDL cholesterol, systolic blood pressure (SBP), and diastolic blood pressure (DBP). CRS was calculated as WC + insulin + glucose + triglycerides - HDL cholesterol + the mean of SBP and DBP. HRV variables (SDNN, RMSSD, HF, LF, LF/HF, Mean RR) were measured using 5-minute electrocardiography at rest and analyzed using the Kubios HRV software. In this cross-sectional study, associations of CRS and individual cardiometabolic risk factors with HRV were investigated using linear regression analyses adjusted for sex and peak height velocity. RESULTS CRS was negatively associated with RMSSD, HF, Mean RR (P value

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow-up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents' socioeconomic position and socioeconomic circumstances in participants' residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow-up (2011) at ages 34-49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18-1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09-1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.

Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3–18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (β=–0.262 SD [95% CI, –0.520 to –0.005]) and serum total cholesterol (β=–0.214 SD [95% CI, –0.365 to –0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (β=–0.407 SD [95% CI, –0.708 to –0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning ( P for trend=0.008; 3 cardiovascular risk factors: β=–0.390 SD [95% CI, –0.691 to –0.088]), with visual processing and sustained attention ( P for trendP for trend=0.048; 2 cardiovascular risk factors: β=–0.164 SD [95% CI, –0.318 to –0.010]). Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3–18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53–0.84; Harmonized criteria), obesity (BMI > 30 kg/m2, RR = 0.76;CI95% = 0.59–0.98), high waist circumference (RR = 0.82;CI95% = 0.69–0.98), and high triglyceride (RR = 0.60;CI95% = 0.47–0.75), insulin (RR = 0.58;CI95% = 0.46–0.74) and glucose (RR = 0.77;CI95% = 0.62–0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLsingle bondC) concentration (RR = 0.78;CI95% = 0.66–0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk. peerReviewed

AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (2), overweight (≥25-2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

BACKGROUND AND OBJECTIVES: Cardiovascular risk factors, such as obesity, blood pressure, and physical inactivity, have been identified as modifiable determinants of left ventricular (LV) diastolic function in adulthood. However, the links between childhood cardiovascular risk factor burden and adulthood LV diastolic function are unknown. To address this lack of knowledge, we aimed to identify childhood risk factors associated with LV diastolic function in the participants of the Cardiovascular Risk in Young Finns Study. METHODS: Study participants (N = 1871; 45.9% men; aged 34–49 years) were examined repeatedly between the years 1980 and 2011. We determined the cumulative risk exposure in childhood (age 6–18 years) as the area under the curve for systolic blood pressure, adiposity (defined by using skinfold and waist circumference measurements), physical activity, serum insulin, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterols. Adulthood LV diastolic function was defined by using E/é ratio. RESULTS: Elevated systolic blood pressure and increased adiposity in childhood were associated with worse adulthood LV diastolic function, whereas higher physical activity level in childhood was associated with better adulthood LV diastolic function (P < .001 for all). The associations of childhood adiposity and physical activity with adulthood LV diastolic function remained significant (both P < .05) but were diluted when the analyses were adjusted for adulthood systolic blood pressure, adiposity, and physical activity. The association between childhood systolic blood pressure and adult LV diastolic function was diluted to nonsignificant (P = .56). CONCLUSIONS: Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.

Background: The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer’s disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-β (Aβ) burden and severe OSA in middle-aged patients. Objective: Examine the possible presence of cortical Aβ accumulation in middle-aged patients with severe OSA. Methods: We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h–1). Known etiological factors for possible Aβ accumulation were used as exclusion criteria. Aβ uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI. Results: When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aβ uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology. Conclusion: Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aβ uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aβ clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated 3H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young's modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis. publishedVersion

Aims/hypothesis We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. Methods We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6–9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. Results Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient β for intervention effect −0.33 [95% CI −0.62, −0.04], p = 0.026) and HOMA-IR (β for intervention effect −0.084 [95% CI −0.156, −0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. Conclusions/interpretation The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. Trial registration ClinicalTrials.gov NCT01803776

Context The influence of dietary pattern trajectories from youth to adulthood on adult glucose metabolism is unknown. Objective To identify dietary pattern trajectories from youth to adulthood and examine their associations with adult impaired fasting glucose (IFG). Methods Thirty-one-year population-based cohort study among 1007 youths aged 3-18 years at baseline in Finland. Diet intake was assessed in 1980, 1986, 2001, 2007, and 2011. Group-based trajectory modelling was used to identify dietary pattern (identified by factor analysis) trajectories. Adult IFG was measured by the latest available data from 2001, 2007, and 2011. Results Among 1007 participants, 202 (20.1%) developed IFG and 27 (2.7%) developed type 2 diabetes in adulthood (mean follow-up of 30.7 years; mean [SD] age 40.5 [5.0] years). Three dietary patterns were identified at baseline and were retained in 1986 and 2001: “Traditional Finnish,” “High carbohydrate,” and “Vegetables and dairy products.” Three different patterns were identified in 2007, which remained similar in 2011: “Traditional Finnish and high carbohydrate,” “Red meat,” and “Healthy.” Trajectories of increased or stably medium “red meat” pattern scores from youth to adulthood were detrimentally associated with IFG (relative risk 1.46, 95% CI 1.12-1.90 for Medium (M)-stable/M-large increase vs low-stable trajectory) after adjusting for confounders. This association was slightly reduced after further adjusting for long-term dietary fiber intake. Conclusion Trajectories of an increased or stably moderate adherence to a “red meat” dietary pattern from youth to adulthood are associated with higher risk of adult IFG. This association is partly explained by low dietary fiber intake.

Context To the best of our knowledge, no previous studies have examined the role of youth calcium intake in the development of impaired glucose metabolism, especially those with long-term high calcium intake. Objectives To examine whether youth and long-term (between youth and adulthood) dietary calcium intake is associated with adult impaired glucose metabolism and type 2 diabetes (T2D). Design, setting, and participants The Cardiovascular Risk in Young Finns Study is a 31-year prospective cohort study (n = 1134; age, 3 to 18 years at baseline). Exposures Dietary calcium intake was assessed at baseline (1980) and adult follow-up visits (2001, 2007, and 2011). Long-term (mean between youth and adulthood) dietary calcium intake was calculated. Main outcome measures Adult impaired fasting glucose (IFG) and T2D. Results We found no evidence for nonlinear associations between calcium intake and IFG or T2D among females and males (all P for nonlinearity > 0.05). Higher youth and long-term dietary calcium intake was not associated with the risk of IFG or T2D among females or males after adjustment for confounders, including youth and adult body mass index. Conclusions Youth or long-term dietary calcium intake is not associated with adult risk of developing impaired glucose metabolism or T2D.

Background and aims In the 1960s and 1970s, Finland, mortality due to coronary heart disease (CHD) was over 30% higher among Finns residing in the east of the country compared with those residing in the west. Today, CHD mortality remains 20% higher among eastern Finns. The higher incidence of CHD mortality among eastern Finns has largely been explained by higher risk factor levels. Using a unique longitudinal cohort, we aimed to determine if participants who resided in eastern Finland during childhood had higher CHD risk factors in adulthood and from childhood to adulthood. Methods The study population included 2063 participants of the Cardiovascular Risk in Young Finns Study, born during the period 1962–1977, with risk factor data available from baseline (1980) when participants were aged 3–18 years, and had risk factor data collected again in adulthood (2011) when aged 34–49 years. Results Adult CHD risk factor profile was similar for those who resided in eastern or western Finland in childhood. Over life-course from 1980 to 2011, those subjects with childhood residency in eastern Finland had, on average, higher systolic (p = 0.006) and diastolic (p = 0.0009) blood pressures, total (p = 0.01) and LDL-cholesterol (p = 0.01), triglycerides (p = 0.04), apoB (p = 0.02), and serum glucose (p Conclusions Our sample of adult Finns aged 34–49 years had a similar CHD risk factor profile irrespective of whether they resided in eastern or western Finland during their childhood. However, when considering participants risk factor profiles over a 31-year period, those who resided in eastern Finland in childhood were associated with a less favorable CHD risk factor profile than those who resided in western Finland in childhood. The observed differences suggest that future CHD mortality might remain higher in eastern Finland compared with western Finland.

Background This study was made to figure out, does low and high estradiol levels during in vitro fertilization (IVF) cycles have a different effect on carotid artery distensibility (Cdis), carotid artery diameter (Cdia), blood pressure and metabolic factors? Can the stimulation protocol be considered safe to women’s vasculature? Methods We studied 28 women having a long agonist protocol IVF-treatment in Kuopio University Hospital during the years 2011–2016. Patients were examined at three time points: in the beginning of their own period (low estradiol), during the gonadotrophin releasing hormone (GnRH) analogue downregulation (low estradiol) and during the follicle stimulating hormone (FSH) stimulation (high estradiol). Women served as their own controls and their menstrual phase (2- to 5-day period after the beginning of menstruation with low estrogen) was used as the reference. Cdis and Cdia were assessed using ultrasound. Blood pressure, weight, estradiol levels and lipids were monitored. Results Cdis, Cdia, systolic and diastolic blood pressures peaked during the GnRH-analogue treatment with the lowest estradiol levels. Cdis, Cdia and systolic blood pressures declined by 11% (P = 0.002), 3,8% (P < 0.001) and 2,5% (P = 0.026) during the FSH-stimulation when the estradiol levels were high. Cdis correlated significantly (P < 0.05) with systolic blood pressure, diastolic blood pressure and triglycerides in high estrogenic environment and with diastolic blood pressure (P < 0.05) when estrogen profiles were low. Conclusions Carotid artery stiffens during the high estradiol levels compared to low levels and this was not explained by the higher diameter of the carotid artery, hyperlipidemia or blood pressure profiles. All the changes in Cdis and Cdia are variations of normal, and if there is no history of cardiovascular problems, it can be considered, that the stimulation protocol is not hazardous to vasculature.

Summary Background & aims The influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes. Methods A population-based prospective cohort study in Finland (n = 1029, aged 3–18 years at baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI). Results There were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption). Conclusions Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.

Though fairly benign reputation, the right bundle branch block (RBBB) can cause left ventricular mechanical dyssynchrony (LVMD). Still, the relationship between electrical disturbance and LVMD is partly unclear among these patients. Thirty patients with RBBB and 60 matching controls were studied with vector electrocardiography and myocardial perfusion imaging phase analysis. RBBB group was divided into those with and those without LVMD. Prevalence of LVMD among RBBB patients was 50% and among controls 22%. Odds ratio (OR) for LVMD in patients with RBBB vs controls without RBBB was 3.6 (95% CI 1.4 to 9.3). Ejection fraction (EF), end-systolic volume, the angle between QRS and T vectors, and the QRS angle in the sagittal plane were significantly different between RBBB patients with and without LVMD. The QRS duration was comparable in these groups. EF associated independently with LVMD, explaining 60% of its variation. A cut-off value of EF ≤ 55% detected LVMD in 100% specificity (sensitivity of 47%). Half of the patients with RBBB had LVMD. The OR for LVMD between RBBB and normal ECG was 3.6. It seems that EF, rather than electrical parameters, is the main determinant of LVMD. This information might be useful when evaluating indications for cardiac resynchronization therapy.

Carotid artery longitudinal wall motion (CALM) is a new biomarker, which can be measured together with carotid intima-media thickness and distensibility measurements in the same session. Our objective was to study the relationship between these indicators of vascular health and cardiovascular risk factors in a large and well-characterized study population.The study population consisted of 465 subjects aged 30-45 years. Successful measurements were performed in 287 participants.The peak-to-peak and retrograde amplitudes of the longitudinal motion were inversely correlated with systolic blood pressure (SBP; r = -0.152, p0.05 and r = -0.189, p0.01), diastolic blood pressure (DBP; r = -0.170, p0.01 and r = -0.256, p0.001) and body mass index (BMI; r = -0.158, p0.01 and r = -0.291, p0.001). In addition, retrograde amplitude of longitudinal motion indirectly correlated with total cholesterol and triglycerides (r = -0.163, p0.01 and r = -0.228, p0.001, respectively). Amplitude of antegrade longitudinal motion was directly correlated with DBP, total cholesterol, LDL-cholesterol, triglycerides and BMI (r = 0.198-0.274, p0.001 for all). Antegrade longitudinal motion increased and retrograde longitudinal motion decreased with the increasing number of cardiovascular risk factors.The magnitude of correlation coefficients between CALM parameters and risk factors was comparable with those for carotid intima-media thickness and distensibility. However, the correlation profile for various risk factors was different and CALM gives additional information regarding arteriosclerosis and risk factors.