Soluble ST2, a biomarker of fibrosis, is associated with multiple risk factors, chronic diseases and total mortality in the OPERA study

Abstract Several diseases have a deleterious fibrosis component. Biomarkers indicating potential clinical utility that reliably reflect the degree of fibrosis have been introduced, one of them being soluble suppression of tumorigenicity 2 (sST2). The aim of our study was to explore the association of cardiometabolic risk factors, different diseases and total mortality with biomarker sST2 and see, how fibrosis is portrayed in these conditions. In addition, we were interested to see if sST2 levels could predict fibrosis in the long-term (21 years). The Oulu Project Elucidating Risk of Atherosclerosis (OPERA) survey collected data on the same individuals in years 1991–1993 (baseline, n = 1045), 2013–2014 (follow-up, n = 600) and mortality data until year 2019. Smoking at baseline retained a significant association with sST2 levels reflecting fibrosis development 20 years later. In the multivariate model male gender, diabetes, quick-index, levels of alanine aminotransferase (ALAT), high-density lipoprotein (HDL) cholesterol and high-sensitivity C-reactive protein (hsCRP) were associated with elevated sST2 levels at the examination 2013–2014. sST2 levels were higher among subjects suffering from cardiovascular disease (p = .031), cancer (p = .021), mild cognitive decline (p = .046) and diabetes (p < .001). Total mortality was assessed by using the Cox proportional hazard survival model analysis. sST2 (log-transformed) was an independent predictor of total mortality (HR 9.4; 95% CI 2.8–31.4, p<.001) when age, gender, diabetes, smoking, quick-index, levels of ALAT, HDL-cholesterol and hsCRP were added as covariates. In addition, elevated levels indicated worse prognosis and predicted mortality

Comparing ultrasonographically assessed carotid and abdominal aorta plaques in cardiovascular disease risk estimation

Abstract Background: Individual risk estimation is an essential part of cardiovascular (CV) disease prevention. Several imaging parameters have been studied for this purpose. Based on mounting evidence, international guidelines recommend the ultrasound assessment of carotid artery plaques to refine individual risk estimation. Previous studies have not compared carotid artery and abdominal aorta plaques in CV risk estimation. Our aim was to explore this matter in a prospective study setting. Methods: Participants were part of the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) project. All participants (n = 1007, 50% males, aged 51.3 ± 6.0 years) were clinically examined in the beginning of 1990’s and followed until the end 2014 for fatal and non-fatal CV events. Results: During a median follow-up of 22.5 (17.5–23.2) years, 246 (24%) participants suffered a CV event and 79 (32%) of those CV events were fatal. When compared to those without plaques, both carotid (hazard ratio, HR 2.854 [95% confidence interval, CI, 2.188–3.721, p < 0.001) and abdominal aorta plaques (HR 2.534 [1.503–4.274], p < 0.001) were major risk factors for CV events as an aggregate endpoint. These associations remained even after adjusting the multivariable models with age, sex, systolic blood pressure, smoking, diabetes, LDL cholesterol, and with previous CV events (coronary artery disease and stroke/transient ischemic attack). However, only carotid plaques were significant risk factors for fatal CV events: multivariable adjusted HR 2.563 (1.452–4.524), p = 0.001. Furthermore, reclassification and discrimination parameters were improved only when carotid plaques were added to a baseline risk model. Adding abdominal aorta plaques to the baseline risk model improved C-statistic from 0.718 (0.684–0.751) to 0.721 (0.688–0.754) whereas carotid plaques improved it to 0.743 (0.710–0.776). Conclusions: Both carotid and abdominal aorta plaques are significant risk factors for CV events, but only carotid plaques provide prognostic information beyond traditional CV risk factors on fatal CV events. If one ultrasound parameter for plaque detection and CV risk estimation had to be chosen, carotid plaques may be preferred over abdominal aorta

Cancer increases the risk of atrial fibrillation during long-term follow-up (OPERA study)

Abstract Introduction: Relation between atrial fibrillation (AF) and cancer is known but not very well understood. The purpose of this prospective study was to find out whether subjects with cancer were at greater risk of AF than subjects without cancer. Materials and methods: The study was based on the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) material and had 1045 subjects and the mean follow-up time of 16.3 years. During the follow-up AF and cancer diagnosis were made (atrial flutter included) if these events were listed in the National Death Registry and/or hospital discharge registry. Results: In this study 130 subjects (12%) had cancer and 19% of these had AF, whereas only 9% of those without cancer experienced AF during the follow-up (p<0.001). Subjects in the cancer group had greater probability of developing atrial fibrillation during the follow-up time in comparison to the subjects without cancer (Hazard ratio (HR) 2.47 (95%CI) 1.57–3.88) in multivariate model including relevant confounding factors. Conclusion: The main finding of this OPERA study was that cancer is an independent risk factor of atrial fibrillation. Still it remains unclear whether this association is causative or whether cancer and atrial fibrillation just share the same pathophysiologic mechanisms

Association between participation in the Northern Finland Birth Cohorts and cardiometabolic disorders

Abstract Background: We studied the association between participation in the longitudinal follow-up study and cardiometabolic disorders in two longitudinal studies which started prospectively in the antenatal period: the Northern Finland Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). Both birth cohorts have been followed up since birth with multiple follow-ups including questionnaires, and clinical examinations. Methods: The NFBC studies were compared to comparison cohorts of individuals who were born in the same area as the study cohorts, but in different years. The data for the comparison cohort were obtained from registers. The cumulative incidence rates of hospital-treated cardiometabolic disorders were calculated for study and comparison cohorts covering the age of 7–50 years in NFBC1966 and the age of 0–29 years in NFBC1986. Cardiometabolic-related causes of death were analysed in NFBC1966 and the comparison cohort from the age of 0–50 years. The analysed cardiometabolic disorders were diabetes mellitus, coronary artery disease, hyperlipidaemia, obesity, hypertension, and cerebrovascular disorders. The risk ratio (RR) with 95% confidence intervals (CI) was calculated by sex. Results: In NFBC1966, no differences in cumulative incidences of cardiometabolic disorders or cardiometabolic-related deaths compared to the comparison cohort were found. Male members of NFBC1986 had decreased risk of obesity (RR: 0.45, 95% CI: 0.27–0.75) and any cardiometabolic disorders (RR: 0.75, 95% CI: 0.59–0.95) compared to the comparison cohort. Conclusions: The results suggest that participation in the NFBC1986 may have a weak positive health effect among men. Agreement to follow-up studies focusing on diet, substance use, and physical activity, may slightly decrease the incident risk of cardiometabolic disorders in the study population

Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

Abstract The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality

Metabolic syndrome but not genetic polymorphisms known to induce NAFLD predicts increased total mortality in subjects with NAFLD (OPERA study)

Abstract Metabolic syndrome (MetS) and genetic polymorphisms PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 are known inductors of non-alcoholic fatty liver disease (NAFLD). However, knowledge about how these affect the mortality of subjects with NAFLD is scarce. Therefore, we investigated the impact of MetS, PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 on overall and cardiovascular disease (CVD) specific mortality among subjects with or without NAFLD. NAFLD diagnosis was based on liver ultrasound at the baseline. After this and other comprehensive examinations, 958 middle-aged Finns, 249 with NAFLD, were followed for 21 years. The mortality data was gathered from the National Death Registry. After multiple adjustments, the NAFLD individuals with MetS had increased risk of overall mortality as compared to the NAFLD subjects without MetS [2.054 (1.011–4.173, p = 0.046)]. However, PNPLA3 rs738409 [1.049 (0.650–1.692, p =0 .844)], TM6SF2 rs58542926 [0.721 (0.369–1.411, p = 0.340)] or MBOAT7 rs641738 [0.885 (0.543–1.439, p = 0.621)] did not affect the overall mortality. MetS was also a marker of increased risk of CVD mortality (15% vs. 2%, p =0.013) while genetic polymorphisms did not affect CVD mortality. In conclusion, MetS, but not the gene polymorphisms studied, predicts increased overall and CVD-specific mortality among NAFLD subjects

Collaborative diabetes training in outpatient primary care

Abstract Two Universities from Oulu, Finland organised integrated and interprofessional (IP) type 2 diabetes training periods for undergraduate medical and nursing students in collaboration with the University Hospital and Health and Wellbeing Centre of Oulu. There is an ongoing health, social services and regional government reform in Finland. The services will be organised in a customer-orientated way and the reform will combine the primary and secondary services. The training was tailored to reflect the real life future setting in Finnish primary care, and this model fits well with the principles of collaborative education. The study aimed at investigating students’ attitudes and readiness for inter professional learning and their learning experience in combined primary and secondary care settings. The second aim was to strengthen students’ professional skills by working with patients in a patient-centred manner. The “Readiness for Interprofessional Learning Scale” was used with added questions about pair training. Students’ perceptions of their clinical skills were evaluated. The students valued the mutual learning experience in outpatient primary care. They felt comfortable with working together and complemented each other. Students performed well with IP competencies such as patient centredness, communication and team functioning. Patients in general were very satisfied with the visit. Teamwork and collaboration, professional identity and pair work were highly scored in both student groups while roles and responsibilities were evaluated a little less positively. Collaboration between different levels of care and health policies is important when developing health professionals’ education. This IP teamwork experience helps both future and current health-care professionals to better organise the care of chronic illnesses

Long-term metabolic fate and mortality in obesity without metabolic syndrome

Abstract Background: Obesity and metabolic syndrome (MetS) are known to expose to atrial fibrillation (AF), cardiovascular diseases (CVD) and mortality. Metabolically healthy obesity refers to obesity without MetS. This study aimed to investigate how obesity and MetS modify the risk of CVD, AF and mortality in very long-time follow-up. Methods: Finnish middle-aged subjects (n = 1045) were grouped into four subgroups according to the presence of obesity and MetS. CVD events and AF were followed for 24 years and total mortality for 30 years. Moreover, 600 available patients had a follow-up visit for metabolic examinations after approximately 22 years. Results: One-hundred and sixty-two (30%) subjects without obesity or MetS died during the follow-up. Ninety-two (17%) of the patients in this group had a CVD event and 58 (11%) were diagnosed with AF. As compared to them, obese subjects without MetS had similar metabolic fate and mortality (mortality 26 (38%), p = .143; CVD event 12 (18%), p = .858 and AF 7 (10%), p = .912, respectively), whereas subjects with obesity and MetS had greater mortality (102 (49%), p < .001), more CVD (71 (34%), p < .001) and AF (49 (23%), p < .001). Non-obese individuals with MetS had greater rates of mortality (96 (44%), p < .001) and CVD (80 (37%), p < .001), but not of AF (26 (12%), p = .606). Of the 40 subjects with obesity but without MetS at baseline and available for the follow-up visit, 15 (38%) were metabolically healthy at the follow-up visit. Conclusions: In the present long-term follow-up study, the presence of MetS, but not obesity only, implies a greater risk of mortality and CVD. The risk of AF is increased only in subjects with both obesity and MetS. However, obesity without MetS tends to progress eventually to obesity with MetS

One-hour post-load glucose improves the prediction of cardiovascular events in the OPERA study

Abstract Background: To estimate the ability of fasting, 1-h, and 2-h post-load glucose to predict cardiovascular outcomes. Methods: We examined a population-based study consisting of 977 middle-aged subjects who underwent an oral glucose tolerance test with glucose values measured at 0, 60, and 120 min. Participants were followed up to 24 years, and cardiovascular outcomes were collected from national registers. Predictive abilities of fasting, 1-h, and 2-h glucose were evaluated alone and in the prediction models with traditional cardiovascular risk factors using Cox proportional hazard models, the likelihood-ratio test, Harrell's concordance index and integrated discrimination improvement. Results: Cardiovascular endpoint occurred in 222 (22.7%) participants during a median follow-up of 19.8 years. In the prognostic models, 1-h glucose (HR 1.67, 95%CI 1.10–2.53), but not fasting or 2-h glucose, predicted cardiovascular events statistically significantly. In addition, when adding glucose parameters into the model including traditional cardiovascular risk factors, only 1-h glucose improved the predictive ability (LR-test p=.046). Finally, 1-h glucose found slightly over 50% more cardiovascular endpoints that were not recognized by fasting or 2-h glucose levels. Conclusions: Our findings support the earlier ones suggesting that 1-h glucose would be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h glucose

Resistin is a risk factor for all-cause mortality in elderly Finnish population:a prospective study in the OPERA cohort

Abstract Objective: Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people. Methods: The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline. Results: After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64–5.56, p<0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577–0.734), p<0.001 and an optimal cutoff value of 12.88 ng/ml. Conclusions: Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors