Showing papers by "Tomi Laitinen published in 2020"

HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study

Abstract: 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.

The Young Finns Study.

Abstract: Acknowledging the lack of previous knowledge, we studied whether childhood/adolescent exposure to parental smoking associates with midlife cognitive function leveraging the data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3-18 years was followed-up between 1980-2011. Cognitive testing was performed in 2011 on 2,026 participants aged 34-49 years using a computerized test. Measures of childhood/adolescent second-hand smoke exposure were parental self-reports of smoking and participants' serum cotinine levels. Participants were classified into: 1)no exposure (non-smoking parents, cotinine<1.0ng/mL); 2)hygienic parental smoking (1-2 smoking parents, cotinine<1.0ng/mL); and 3)non-hygienic parental smoking (1-2 smoking parents, cotinine ≥1.0ng/mL). Analyses were adjusted for sex, age, family socio-economic status, polygenic risk score for cognitive function, adolescence/adulthood smoking, blood pressure and serum total cholesterol. Compared with non-exposed, participants exposed to non-hygienic parental smoking were at higher relative risk (RR) for poor (lowest quartile) midlife episodic memory and associative learning (RR=1.38, 95%CI=1.08-1.75) and a weak association was found for short term and spatial working memory (RR=1.25, 95%CI=0.98-1.58). The associations for those exposed to hygienic parental smoking were non-significant (episodic memory and associative learning: RR=1.19, 95%CI=0.92-1.54; short term and spatial working memory: RR=1.10, 95%CI=0.85-1.33). Avoiding childhood/adolescence second-hand smoking exposure promotes adulthood cognitive function.

Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review.

Abstract: 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.

Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene.

Abstract: Objective To investigate whether the Ala143Thr variant of the α-galactosidase A gene (A143T/GLA), with conflicting interpretations of pathogenicity, is associated with Fabry cardiomyopathy. Methods The index patient, a woman in her 60s with cardiomyopathy, was screened for variants in 59 cardiomyopathy-related genes. A143T/GLA, the only rare variant found, was screened in 10 relatives. GLA activity and lyso-Gb3 levels were measured and echocardiography was performed in 8 of 9 subjects carrying A143T/GLA. Cardiac magnetic resonance (CMR) imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) were performed in four adult A143T/GLA carriers. Endomyocardial biopsy was obtained from two adult A143T/GLA carrying sons of the index patient. Results The index patient and her elder son had a pacemaker implantation because of sick sinus syndrome and atrioventricular block. GLA activities were decreased to 25%–40% of normal in both sons and one granddaughter. Lyso-Gb3 levels were elevated in both sons. In CMR, the index patient and her two sons had left ventricular (LV) hypertrophy and/or dilatation. The elder son had late gadolinium enhancement, high CMR-derived T1 time and positive FDG signal in PET/CT in the basal inferolateral LV wall. The younger son had low T1 time and the mother had positive FDG signal in PET/CT in the basal inferolateral LV wall. Endomyocardial biopsy of both sons showed myocardial accumulation compatible with glycolipids in light and electron microscopy, staining with anti-Gb3 antibody available for the younger son. Five female relatives with A143T/GLA had no cardiomyopathy in cardiac imaging. Conclusions A143T/GLA is likely a late-onset Fabry cardiomyopathy causing variant with incomplete penetrance.

Childhood Exposure to Parental Smoking and Midlife Cognitive Function.

Abstract: 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 <1.0 ng/mL); 2) hygienic parental smoking (1-2 smoking parents, cotinine <1.0 ng/mL); and 3) nonhygienic parental smoking (1-2 smoking parents, cotinine ≥1.0 ng/mL). Analyses adjusted for sex, age, family socioeconomic status, polygenic risk score for cognitive function, adolescent/adult smoking, blood pressure, and serum total cholesterol level. Compared with the nonexposed, participants exposed to nonhygienic parental smoking were at higher risk of poor (lowest quartile) midlife episodic memory and associative learning (relative risk (RR) = 1.38, 95% confidence interval (CI): 1.08, 1.75), and a weak association was found for short-term and spatial working memory (RR = 1.25, 95% CI: 0.98, 1.58). Associations for those exposed to hygienic parental smoking were nonsignificant (episodic memory and associative learning: RR = 1.19, 95% CI: 0.92, 1.54; short-term and spatial working memory: RR = 1.10, 95% CI: 0.85, 1.34). We conclude that avoiding childhood/adolescence secondhand smoke exposure promotes adulthood cognitive function.

CVD risk factors and surrogate markers - Urban-rural differences:

Abstract: Aims: Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban-rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). Methods: The study population comprised 2903 participants (54.1% female, mean age 10.5 years in 1980) of the Cardiovascular Risk in Young Finns Study who had been clinically examined in 1980 (age 3-18 years) and had participated in at least one adult follow-up (2001-2011). Results: In adulthood, urban residents had lower systolic blood pressure (-1 mmHg), LDL-cholesterol (-0.05 mmol/l), lower body mass index (-1.0 kg/m2) and glycosylated haemoglobin levels (-0.05 mmol/mol), and lower prevalence of metabolic syndrome (19.9 v. 23.7%) than their rural counterparts. In addition, participants continuously living in urban areas had significantly lower IMT (-0.01 mm), LVM (1.59 g/m2.7) and pulse wave velocity (-0.22 m/s) and higher carotid artery compliance (0.07%/10 mmHg) compared to persistently rural residents. The differences in surrogate markers of CVD were only partially attenuated when adjusted for cardiovascular risk factors. Conclusions: Participants living in urban communities had a more favourable cardiovascular risk factor profile than rural residents. Furthermore, participants continuously living in urban areas had less subclinical markers related to CVD compared with participants living in rural areas. Urban-rural differences in cardiovascular health might provide important opportunities for optimizing prevention by targeting areas of highest need.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

Abstract: 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. 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. 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. 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. ClinicalTrials.gov NCT01803776

Associations of cardiometabolic risk factors with heart rate variability in 6‐ to 8‐year‐old children: The PANIC Study

Abstract: 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 < .05) and positively with LF/HF (P value = .005). Insulin was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05) and positively with LF/HF (P value = .008). SBP was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05). DBP was negatively associated with SDNN, RMSSD, and Mean RR (P value < .05). WC, glucose, triglycerides, or HDL cholesterol were not associated with HRV variables. CONCLUSIONS Higher CRS, insulin, and blood pressure were associated with smaller HRV, mainly indicating lower parasympathetic activity, in young children. This knowledge may help improving the clinical management of metabolic syndrome and cardiovascular diseases since childhood.

Childhood Oral Infections Associate with Adulthood Metabolic Syndrome: A Longitudinal Cohort Study.

Abstract: 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.

Association of Body Mass Index in Youth With Adult Cardiometabolic Risk.

Abstract: Background Whether long-term exposure to overweight or obesity from early life to adulthood has a detrimental influence on health outcomes is unknown. We aimed to investigate whether duration of overweight or obesity from youth to adulthood is associated with adult cardiometabolic risk. Methods and Results A population-based cohort study was performed of 1268 youths, aged 3 to 18 years, with follow-ups at 3, 6, 9, 12, 21, 27, and 31 years. Duration of overweight or obesity over 31-year follow-up was calculated. Adulthood outcomes included type 2 diabetes mellitus, impaired fasting glucose, high insulin levels, high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity, carotid artery compliance, Young elastic modulus, and stiffness index. Rates of overweight/obesity were 7.9% at baseline and 55.9% after 31 years. After adjustment for confounders, longer duration of overweight or obesity was associated with increased risk of all outcomes (relative risk ranged from 1.45-9.06 for type 2 diabetes mellitus, impaired fasting glucose, carotid intima-media thickness, hypertension, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; β from 0.370-0.543 m/s for pulse wave velocity; -0.193 to -0.237 %/10 mm Hg for carotid artery compliance; 52.1-136.8 mm Hg·mm for Young elastic modulus; and 0.554-0.882 for stiffness index). When body mass index was further adjusted, these associations disappeared or were substantially reduced. Detrimental associations of adult body mass index with all outcomes were robust to adjustment for confounders and duration of overweight or obesity. Conclusions Overweight or obesity in adulthood rather than childhood appears to be more important for adult cardiometabolic health.

The effect of different estradiol levels on carotid artery distensibility during a long agonist IVF protocol

Abstract: 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? 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. 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. 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.

Divergent pathologies and treatment options for diabetic neuropathies.

Abstract: To the Editor: In an excellent review on polyneuropathy in patients with diabetes, Callaghan et al [1] question the significance of hyperglycaemia in the prevention and treatment of neuropathy in individuals with type 2 diabetes. They concluded that intensive glycaemic control only marginally improved neuropathy in type 2 diabetes cohorts. This viewwas based on the lack of definitive evidence from a small number of intervention studies in individuals with type 2 diabetes, and the conclusions depended heavily on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which accounted for 70.6% of the evidence [2]. There are many reasons for this quite modest level of evidence, as also discussed by the authors. Furthermore, we should keep in mind that the aetiology of type 2 diabetes is heterogeneous based on recent genetic studies, and that the phenotype is also variable, ranging from relative insulin deficiency to marked insulin resistance, commonly associated with obesity. In line with the heterogenous nature of the disease, in 1995 we published a 10-year follow-up study on the development of neuropathy in newly diagnosed individuals with type 2 diabetes [3]. The diagnosis was based on both clinical symptoms and signs, and neurophysiological measurements during follow up, making this study unique in the field. There was a remarkable increase in the development of neuropathy in diabetic individuals from baseline (8.3%) to 10-year examination (41.9%). In the non-diabetic control group, the respective figures were 2.1% and 5.8%. Besides hyperglycaemia, low fasting and postprandial insulin and C-peptide values were, independently of glucose values, associated with the risk of peripheral somatic neuropathy. We suggested that, in individuals with type 2 diabetes, good glycaemic control should be maintained from the time of diagnosis. Patients who develop marked insulin deficiency should be treated with insulin therapy to correct hyperglycaemia in order to prevent neuropathy, due to the known beneficial effects of insulin on hyperglycaemia and a potential role of insulin deficiency, per se in the pathophysiology of diabetic neuropathy [3]. It is of note that, on average, metabolic control in individuals with type 2 diabetes was quite poor in 1990s as compared with present day, which may explain the observed clear relationship between glucose values and the long-term risk of neuropathy in our study [3]. Callaghan et al barely mention diabetic autonomic neuropathy as a part of the diabetic neuropathy concept [1]. Autonomic neuropathy may have different pathologies to peripheral neuropathy. We consider autonomic neuropathy underdiagnosed concerning its multiple clinical manifestations. Furthermore, cardiac autonomic neuropathy is associated with an increased cardiovascular morbidity and mortality risk in individuals with diabetes. In our study on newly diagnosed patients with type 2 diabetes [4], both hyperglycaemia and high insulin values were associated with the risk of autonomic neuropathy, strongly suggesting that insulin resistance plays a role in the pathogenesis of autonomic nervous dysfunction among obese individuals with type 2 diabetes. We suggested divergent pathologies for autonomic and * Matti Uusitupa matti.uusitupa@uef.fi