Elina Jokinen

The 21‐year follow‐up of the Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east–west difference

Objectives.  The Cardiovascular Risk in Young Finns Study is an on‐going multicentre study of atherosclerosis precursors in Finnish children and young adults. We have collected risk factor data in the 21‐year follow‐up performed in 2001. The aims of this analysis were to examine the levels, secular trends and east–west difference in risk factors amongst young adults.

Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study.

Indoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up‐regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima‐media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglyceride, high sensitive C‐reactive protein (CRP), body mass index (BMI), waist circumference, waist‐to‐hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL‐C, BMI, weakly with CRP and inversely with HDL‐C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL‐C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females.

Follow‐ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6‐year changes in risk factors

Abstract.  Raiko JRH, Viikari JSA, Ilmanen A, Hutri‐Kähönen N, Taittonen L, Jokinen E, Pietikäinen M, Jula A, Loo B.‐M, Marniemi J, Lehtimäki T, Kähönen M, Rönnemaa T, Raitakari OT, Juonala M (University of Turku; University of Tampere and Tampere University Hospital, Tampere; University of Oulu, Oulu; Vaasa Central Hospital, Vaasa; University of Helsinki, Helsinki; and Center of Social and Health Services, Kuopio; Finland). Follow‐ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6‐year changes in risk factors. J Intern Med 2010; 267: 370–384.

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study

Background/Objectives:Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity.Subjects/Methods:Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult.Results:Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21–31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age.Conclusions:Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

Comparison of outcome and clinical characteristics of bacteremia caused by methicillin-resistant, penicillin-resistant and penicillin-susceptible Staphylococcus aureus strains

Abstract Background: The aim of this study was to assess the association of methicillin resistance and penicillinase production with clinical characteristics and outcome of Staphylococcus aureus bacteremia. Methods: For 126 patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, 378 age- and gender-matched controls with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia were selected. Of controls, 126 had bacteremia caused by penicillin-susceptible strains (PSSA) and 252 by penicillinase-producing strains (PRSA). Underlying diseases, clinical course and mortality were retrospectively assessed. Results: Patients with MRSA bacteremia were more often smokers than patients with MSSA bacteremia (OR 2.34, 95% CI 1.27–4.32). MRSA bacteremia was more often healthcare-associated (OR 4.23, 95% CI 2.47–7.24), associated with central venous catheters (OR 2.09, 95% CI 1.27–3.47), glucocorticoid therapy (OR 1.82, 95% CI 1.12–2.93) and prior surgery (OR 2.32, 95% CI 1.43–3.76). Patients with MRSA bacteremia received appropriate empiric antibiotic (31%) less often than controls (98%). Mortality within 28 days was higher in MRSA bacteremia (26.8%) than in MSSA bacteremia (15.5%) (OR 2.00, 95% CI 1.20–3.34), PRSA bacteremia (17.0%) (OR 1.79 95% CI 1.04–3.09) or PSSA bacteremia (12.5%) (OR 2.56 95% CI 1.27–5.15). The difference remained after adjusting for underlying diseases and foci. There was no significant difference in clinical course between PRSA and PSSA bacteremias. Conclusions: MRSA bacteremia was associated with poorer outcome than either PRSA or PSSA bacteremia. We corroborated several risk factors found in previous studies.

Combined interventions are effective in MRSA control.

Abstract Background: A large healthcare-associated epidemic mainly caused by one methicillin-resistant Staphylococcus aureus (MRSA) strain broke out in Pirkanmaa County, Finland, in 2001. This study describes the impact of infection control and screening practices on the epidemic. Methods: The number of hospital-acquired (HA)-MRSA findings obtained from clinical and screening samples during the epidemic was calculated. Strains were typed by pulsed-field electrophoresis (PFGE) or spa typing. Strain type distribution was studied in relation to sample type, year of the epidemic and site of transmission. Several infection control interventions were launched stepwise and screening protocols were expanded. Results: A total of 4118 cases were identified during 2001–2014, of which 3527 were classified as HA. One strain (spa t067) dominated in the epidemic. HA-MRSA cases decreased constantly from the year 2011. The number of new HA-MRSA cases was 57% less in the year 2014 (n = 171) as compared with the year 2011 (n = 399). The proportion of the epidemic strain declined significantly over the years. Screening samples comprised 71% (2439/3527) and clinical samples 29% (1034/3527) of HA-MRSA findings. The number of HA-MRSA cases found from clinical samples started to decrease when screening was expanded. An increase in hand-rub consumption was associated with a decrease in transmissions in Tampere University Hospital (TAUH). Conclusion: Implementation of universal screening together with several other interventions is effective in containing an MRSA epidemic. The proportion of other than Pirkanmaa epidemic (PE)-MRSA strain findings increased throughout the period, indicating the changing epidemiology of MRSA.

Trends in incidence and resistance patterns of Staphylococcus aureus bacteremia

Abstract Background: Staphylococcus aureus bacteremia (SAB) causes a significant burden on the population. Several infection control measures have been implemented in Pirkanmaa county to combat a local epidemic with methicillin-resistant Staphylococcus aureus (MRSA). We aimed to study the epidemiology of SAB and antibiotic resistance of S. aureus and the possible influence of improved infection control. Methods: Register data from 2005 to 2015 were retrospectively analysed to study the antimicrobial susceptibility, the incidence and mortality in SAB in a population-based setting. Results: The incidence of SAB increased during the study period from 21.6 to 35.8/100,000 population. The number of both health care-associated (HA) and community-associated (CA) cases has increased. The incidence of MSSA bacteremia increased from 19.9 to 35.2/100,000 population in Pirkanmaa in parallel to other parts of Finland. The incidence of MRSA bacteremia was 10-fold (4.5/100,000 population) higher in 2011 than in other parts of the country, but sank to the national level (0.59/100,000 population) in 2015. The fatality rate decreased from 22% to 17%. The proportion of penicillin-susceptible Staphylococcus aureus (PSSA) increased from 23.9% in 2008 to 43.1% in 2015. Conclusion: The incidence of both HA and CA SAB has increased since 2005. Conversely, the proportion of MRSA and PRSA bacteremia has decreased. Promotion of infection control measures may have reduced the incidence of MRSA bacteremia but not the overall incidence of SAB. The rising proportion of PSSA enables the use of targeted, narrow spectrum antimicrobials.

Geographic origin as a determinant of left ventricular mass and diastolic function – the Cardiovascular Risk in Young Finns Study:

Aims: Eastern Finns have higher risk of coronary heart disease (CHD) and carotid intima-media thickness than western Finns although current differences in CHD risk factors are minimal. Left ventricular (LV) mass and diastolic function predict future cardiovascular events but their east–west differences are unknown. We examined the association of eastern/western baseline origin with LV mass and diastolic function. Methods : The study population included 2045 subjects of the Cardiovascular Risk in Young Finns Study with data from the baseline survey (1980) and the latest follow-up (2011) when echocardiography was performed at the age of 34–49 years. Results: Subjects with eastern baseline origin had in 2011 higher LV mass (139±1.0 vs. 135±1.0 g, p=0.006) and E/e′-ratio indicating weaker LV diastolic function (4.86±0.03 vs. 4.74±0.03, p=0.02) than western subjects. Results were independent of age, sex, area of examination and CHD risk factors such as blood pressure and BMI (LV mass indexed with height: p<0.0001; E/e′-ratio: p=0.01). LV end-diastolic volume was higher among subjects with eastern baseline origin (135±0.9 vs. 131±0.9 ml, p=0.0011) but left atrial end-systolic volume, also indicating LV diastolic function, was not different between eastern and western subjects (43.4±0.5 vs. 44.0±0.5 ml, p=0.45). Most of the subjects were well within the normal limits of these echocardiographic measurements. Conclusions: In our healthy middle-aged population, geographic origin in eastern Finland associated with higher LV mass compared to western Finland. Higher E/e′-ratio suggests that subjects with eastern baseline origin might have higher prevalence of diastolic dysfunction in the future than western subjects.

East–west differences and migration in Finland: Association with cardiometabolic risk markers and IMT. The Cardiovascular Risk in Young Finns Study

Background: Coronary heart disease mortality has been internationally high in eastern Finland. The excessive mortality risk in Eastern compared with western Finns is explained by differences in cardiometabolic risk profile. Current risk profile differences and association with migration have not been reported. We examined the association of place of residence (east–west) and specifically migration with cardiometabolic risk markers and carotid intima–media thickness (IMT). Methods: The study population included 2204 participants with data available from childhood/youth in 1980 and follow-up examination in 2007. Results: Participants residing in eastern Finland in adulthood had 0.022±0.004mm higher IMT than Western participants. Those who migrated east-to-west had lower IMT than those staying in the east (0.027±0.006mm, p<0.0001) while no difference to those continuously living in the west was found. Those who moved east-to-west had a lower body mass index (25.3±4.3 kg/m2 vs. 26.2±4.5kg/m2, p=0.01), waist circumference (85.7±12.8cm vs. 88.6±12.8cm, p=0.001), prevalence of metabolic syndrome (13% vs. 21%, p=0.01), and higher socioeconomic status (16.6±3.3 vs. 15.0±3.3 school years, p<0.0001) than those who stayed in the east. Conclusions: Higher IMT was found in eastern Finns than in western Finns. Participants who migrated east-to-west had a lower IMT and a better cardiometabolic risk profile than those who stayed in the east.