Browsing by Subject "CARDIOVASCULAR RISK"

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  • Acosta, Tania; Barengo, Noel C.; Arrieta, Astrid; Ricaurte, Carlos; Tuomilehto, Jaakko O. (2018)
    Type 2 diabetes (T2D) imposes a heavy public health burden in both developed and developing countries. It is necessary to understand the effect of T2D in different settings and population groups. This report aimed to present baseline characteristics of study participants in the demonstration area for the Type 2 Diabetes Prevention in Barranquilla and Juan Mina (DEMOJUAN) project after randomization and to compare their fasting and 2-hour glucose levels according to lifestyle and T2D risk factor levels. The DEMOJUAN project is a randomized controlled field trial. Study participants were recruited from study sites using population-wide screening using the Finnish Diabetes Risk Score (FINDRISC) questionnaire. All volunteers with FINDRISC of >= 13 points were invited to undergo an oral glucose tolerance test (OGTT). Participant inclusion criteria for the upcoming field trial were either FINDRISC of >= 13 points and 2-hour post-challenge glucose level of 7.0 to 11.0mmol/L or FINDRISC of >= 13 points and fasting plasma glucose level of 6.1 to 6.9mmol/L. Lifestyle habits and risk factors for T2D were assessed by trained interviewers using a validated questionnaire. Among the 14,193 participants who completed the FINDRISC questionnaire, 35% (n=4915) had a FINDRISC score of >= 13 points and 47% (n=2306) agreed to undergo the OGTT. Approximately, 33% (n=772) of participants underwent the OGTT and met the entry criteria; these participants were randomized into 3 groups. There were no statistically significant differences found in anthropometric or lifestyle risk factors, distribution of the glucose metabolism categories, or other diabetes risk factors between the 3 groups (P>.05). Women with a past history of hyperglycaemia had significantly higher fasting glucose levels than those without previous hyperglycaemia (103 vs 99mg/dL; P Lifestyle habits and risk factors were evenly distributed among the 3 study groups. No differences were found in fasting or 2-hour glucose levels among different lifestyle or risk factor categories with the exception of body mass index, past history of hyperglycaemia, and age of 64 years in women.
  • Loukola, Anu; Buchwald, Jadwiga; Gupta, Richa; Palviainen, Teemu; Hallfors, Jenni; Tikkanen, Emmi; Korhonen, Tellervo; Ollikainen, Miina; Sarin, Antti-Pekka; Ripatti, Samuli; Lehtimaki, Terho; Raitakari, Olli; Salomaa, Veikko; Rose, Richard J.; Tyndale, Rachel F.; Kaprio, Jaakko (2015)
    Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70-0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FIN-RISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.
  • Service, S. K.; Verweij, K. J. H.; Lahti, J.; Congdon, E.; Ekelund, J.; Hintsanen, M.; Räikkönen, Katri; Lehtimaki, T.; Kahonen, M.; Widen, E.; Taanila, A.; Veijola, J.; Heath, A. C.; Madden, P. A. F.; Montgomery, G. W.; Sabatti, C.; Jarvelin, M-R; Palotie, A.; Raitakari, O.; Viikari, J.; Martin, N. G.; Eriksson, J. G.; Keltikangas-Järvinen, Liisa; Wray, N. R.; Freimer, N. B. (2012)
  • LifeLines Cohort Study; Sung, Yun Ju; Heikkinen, Sami; Koistinen, Heikki A. (2019)
    Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P <5 x 10(-8), false discovery rate <0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
  • Elovainio, Marko; Hakulinen, Christian; Pulkki-Raback, Laura; Juonala, Markus; Raitakari, Olli T. (2020)
    We modeled early psychosocial risks as a network of interconnected variables to study their associations with later depressive symptoms and cardiometabolic outcomes. The participants were a nationally representative sample of 2580 men and women aged 3-18 years in 1980. Their parents reported the psychosocial risks in 1980, including the following: (1) child-specific life events, (2) parental health behavior, (3) parental socioeconomic status, and (4) parental psychological problems. Adulthood depressive symptoms and cardiometabolic outcomes were measured in 2007-2012. The most central risks (most number of connections to other risks) were socioeconomic risks that also predicted health outcomes more consistently than others.
  • Kashani-Sabet, Mohammed; Sagebiel, Richard W.; Joensuu, Heikki; Miller, James R. (2013)
  • Hintsanen, Mirka; Kivimäki, Mika; Hintsa, Taina; Theorell, T.; Elovainio, Marko; Raitakari, O. T.; Viikari, J. S. A.; Keltikangas-Järvinen, Liisa (2010)
  • Bogl, Leonie H.; Kaye, Sanna M.; Ramo, Joel T.; Kangas, Antti J.; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietilainen, Kirsi H. (2016)
    Objective. To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Subjects and methods. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (r(g)) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >= 3 kg/m(2)). Results. Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (r(g) = 0.40), glycoprotein (r(g) = 0.37), serum triglycerides (r(g) = 0.36), BCAAs (r(g) = 0.30-0.40), HDL particle diameter (r(g) = -0.33) and HDL cholesterol (r(g) = -0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. Conclusions. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. (C) 2015 Elsevier Inc. All rights reserved.
  • Lindbohm, Joni; Korja, Miikka; Jousilahti, Pekka; Salomaa, Veikko; Kaprio, Jaakko (2018)
    Background and aims: Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. Methods: The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. Results: One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00-1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07-1.55)) and men (HR 1.20 (95% CIs 1.14-1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74-0.97)) and men (HR 0.88 (95% CIs 0.76-1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01-1.31) and HR 1.26 (95% CIs 1.10-1.44) per one SD increase. Age did not change these findings. Conclusions: An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. (C) 2018 Elsevier B.V. All rights reserved.
  • Nath, Artika P.; Ritchie, Scott C.; Byars, Sean G.; Fearnley, Liam G.; Havulinna, Aki S.; Joensuu, Anni; Kangas, Antti J.; Soininen, Pasi; Wennerstrom, Annika; Milani, Lili; Metspalu, Andres; Mannisto, Satu; Wurtz, Peter; Kettunen, Johannes; Raitoharju, Emma; Kahonen, Mika; Juonala, Markus; Palotie, Aarno; Ala-Korpela, Mika; Ripatti, Samuli; Lehtimaki, Terho; Abraham, Gad; Raitakari, Olli; Salomaa, Veikko; Perola, Markus; Inouye, Michael (2017)
    Background: Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. Results: We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. Conclusions: This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.
  • Ahola, Aila J.; Saraheimo, Markku; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Aims: Inflammation plays an important role in the pathogenesis of cardiovascular diseases. Diet, as a modifiable risk factor, may in turn impact systemic inflammation. We therefore assessed whether adherence to the dietary recommendations is associated with high-sensitivity C-reactive protein (hs-CRP) concentrations in type 1 diabetes. Methods: Cross-sectional data from 677 FinnDiane study participants (48% men, mean +/- standard deviation age 46 +/- 13 years) were included. Dietary intake was assessed with a self-administered questionnaire. A diet score, with higher values denoting better adherence to the recommendations, was calculated. Serum hs-CRP concentration was measured, and individuals with hs-CRP <1.0 mg/l, and hs-CRP > 3.0 but <10.0 mg/l were compared. Results: Men and women with high hs-CRP had higher BMI, waist circumference, and triglyceride concentration, but lower HDL-cholesterol concentration. Adjusted for BMI, mean diet score was higher in the low hs-CRP group, both in men (10.8 +/- 3.6 vs. 9.9 +/- 3.8, p = 0.023) and women (12.7 +/- 3.4 vs. 11.6 +/- 3.5, p = 0.021). After further adjustments with potential confounding factors, the difference remained significant only in men. Conclusions: A diet that more closely adheres to the dietary recommendations is associated with lower hs-CRP in men. A prudent diet may help reduce systemic inflammation in type 1 diabetes. (C) 2017 Elsevier B.V. All rights reserved.
  • Takatalo, Jani; Karppinen, Jaro; Taimela, Simo; Niinimaki, Jaakko; Laitinen, Jaana; Sequeiros, Roberto Blanco; Samartzis, Dino; Korpelainen, Raija; Nayha, Simo; Remes, Jouko; Tervonen, Osmo (2013)
  • Nyberg, Solja T.; Singh-Manoux, Archana; Pentti, Jaana; Madsen, Ida E. H.; Sabia, Severine; Alfredsson, Lars; Bjorner, Jakob B.; Borritz, Marianne; Burr, Hermann; Goldberg, Marcel; Heikkila, Katriina; Jokela, Markus; Knutsson, Anders; Lallukka, Tea; Lindbohm, Joni; Nielsen, Martin L.; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H.; Rahkonen, Ossi; Rugulies, Reiner; Shipley, Martin J.; Sipila, Pyry N.; Stenholm, Sari; Suominen, Sakari; Vahtera, Jussi; Virtanen, Marianna; Westerlund, Hugo; Zins, Marie; Hamer, Mark; Batty, G. David; Kivimäki, Mika (2020)
    This cohort study examines disease-free life-years in participants with varying combinations of lifestyle risk factors. Question Are different combinations of lifestyle factors associated with years lived without chronic diseases? Findings In a multicohort study of 116 & x202f;043 participants, a statistically significant association between overall healthy lifestyle score and an increased number of disease-free life-years was noted. Of 16 different lifestyle profiles studied, the 4 that were associated with the greatest disease-free life years included body mass index lower than 25 and at least 2 of 3 factors: never smoking, physical activity, and moderate alcohol consumption. Meaning Various healthy lifestyle profiles appear to be associated with extended gains in life lived without type 2 diabetes, cardiovascular and respiratory diseases, and cancer. Importance It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 & x202f;043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results Of the 116 & x202f;043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 & x202f;911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 & x202f;383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P <.001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex. Conclusions and Relevance In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.
  • Urtamo, Annele; Kautiainen, Hannu; Pitkala, Kaisu H.; Strandberg, Timo E. (2018)
    Personal values influence behavior and decision making, but their long-term associations with health-related quality of life (HRQoL), frailty, and mortality are less clear. We studied these associations from midlife to old age in a 26-year follow-up of the Helsinki Businessmen Study (HBS) cohort. In 1974, 1320 clinically healthy men (born 1919-1934) reported in a 12-item questionnaire their personal values. In 2000, a mailed questionnaire, including assessment of HRQoL with RAND-36 (SF-36) instrument, was sent to survivors, and 1025 men responded. In 2000, the presence of phenotypic frailty was assessed using modified Fried criteria including indicators of shrinking, physical weakness, exhaustion, and physical inactivity. Mortality through December 31, 2000 was verified from national registries. Using a factor analysis, the data of the 12-item questionnaire of personal values were loaded in 3 factors: valuing health ("Health"), enjoyable and varying life ("Enjoyment"), and comfort and work-oriented life ("Work-life-balance"). Adjusted for age, we found a significant positive association between valuing "Health" in midlife and RAND-36 domains of Physical functioning (p = .032) and Vitality (p = .005) in old age. "Health" also predicted less frailty (p = .008), and "Enjoyment" was associated with higher mortality (p = .017). Value priorities of men assessed in midlife had long-term associations with HRQoL and frailty in old age, and they may also predict mortality.
  • Bonamy, Anna-Karin Edstedt; Mohlkert, Lilly-Ann; Hallberg, Jenny; Liuba, Petru; Fellman, Vineta; Domellof, Magnus; Norman, Mikael (2017)
    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
  • Saarinen, Aino I. L.; Keltikangas-Järvinen, Liisa; Honda, Yukiko; Oksman, Elli; Raitakari, Olli; Pulkki-Råback, Laura; Hintsanen, Mirka (2020)
    This study investigated whether breastfeeding predicts offspring’s dispositional compassion and empathy from early adulthood to middle age. The parents of the participants (N = 1,394) of the Young Finns study answered questions about breastfeeding in 1983, and the participants’ compassion and empathy were evaluated in 1997‒2012 (participants were aged 20‒50 years). Breastfeeding did not predict the course of compassion or empathy in adulthood at the age of 20‒50 years. The associations remained non‐significant, when adjusted for age, gender, socioeconomic factors, and a wide range of characteristics of the family environment (including mother’s gestational age; premature birth; birth weight; number of other children at home; parental mental disorder; parental relationship status; parental postnatal smoking; parental postnatal alcohol use; parenting behavior; and child’s externalizing behavior). In conclusion, breastfeeding seems not to predict offspring’s compassion or empathy in adulthood. The findings may present a hopeful perspective for children growing up with non‐breastfeeding caregivers.
  • Liimatta, Jani; Utriainen, Pauliina; Laitinen, Tomi; Voutilainen, Raimo; Jääskeläinen, Jarmo (2019)
    Context: Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown. Objective: To study cardiometabolic profile in adult women with previous PA. Design and participants: Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood. Main outcome measures: Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors. Results: There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; P = 0.014) and acanthosis nigricans (P = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) P = 0.011] and Homeostatic Model Assessment of Insulin Resistance (P = 0.044; BMI-adjusted P = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found. Conclusion: PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors. Copyright (C) 2019 Endocrine Society
  • Paju, Susanna; Pietiäinen, Milla; Liljestrand, John; Lahdentausta, Laura; Salminen, Aino; Kallio, Elisa; Mäntylä, Päivi; Buhlin, Kåre; Hörkkö, Sohvi; Sinisalo, Juha; Pussinen, Pirkko (2021)
    Aim To study the prevalence of carotid artery calcification (CAC) in relation to apical and marginal periodontitis, subgingival dysbiotic bacterial species and serum and saliva immune responses against them. In addition, the aim was to analyse the association of CAC with angiographically verified coronary artery disease (CAD) and mortality. Methodology In the present random Parogene cohort, the patients had an indication for coronary angiography. Apical and marginal periodontitis were diagnosed during clinical and radiographic oral examinations, and CAC on panoramic radiographs (n = 492). Presence and severity of CAD were registered from angiography. Subgingival dysbiotic bacterial species were quantitated using checkerboard DNA-DNA-hybridization, and serum and saliva antibody levels were determined by immunoassays. The cohort was followed-up for 10 years or until death (median 9.9, range 0.21-10.4) via linkage to the national death register. The statistical models were adjusted for age, gender, smoking, hypertension, diabetes and dyslipidemia. Results A total of 102 (20.7%) patients had detectable CAC, which was moderate in 81 (16.4%) and severe in 21 (4.3%). CAC was associated (OR, 95% CI) with severe apical periodontitis (2.25, 1.15-4.41), root canal fillings (1.15, 1.04-1.26), alveolar bone loss (2.66, 1.21-5.84), severe periodontal inflammation (2.23, 1.11-4.47), high level of gram-negative subgingival species (2.73, 1.34-5.50), saliva IgG against dysbiotic species (1.05, 1.01-1.10/unit) and severe (2.58, 1.36-4.90) and chronic (2.13, 1.15-3.93) CAD. A total of 105 (20.7%) patients died during the follow-up and 53 (10.4%) deaths were because of cardiovascular diseases (CVD). Severe CAC predicted worse survival with HRs (95% CI) of 3.08 (1.58-6.06) for all-cause and 3.43 (1.42-8.25) for CVD death. Conclusions CAC on panoramic tomography was associated with (i) apical and marginal periodontitis and dysbiotic bacterial species giving rise to an immunological response, and with (ii) severe, chronic CAD and increased mortality. The results further emphasize the role of oral infections in CAD and the importance of referring a patient with CAC for a cardiovascular evaluation.
  • Vogt, Susanne; Wahl, Simone; Kettunen, Johannes; Breitner, Susanne; Kastenmueller, Gabi; Gieger, Christian; Suhre, Karsten; Waldenberger, Melanie; Kratzsch, Juergen; Perola, Markus; Salomaa, Veikko; Blankenberg, Stefan; Zeller, Tanja; Soininen, Pasi; Kangas, Antti J.; Peters, Annette; Grallert, Harald; Ala-Korpela, Mika; Thorand, Barbara (2016)
    Background: Numerous observational studies have observed associations between vitamin D deficiency and cardiometabolic diseases, but these findings might be confounded by obesity. A characterization of the metabolic profile associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in general and stratified by abdominal obesity, may help to untangle the relationship between vitamin D, obesity and cardiometabolic health. Methods: Serum metabolomics measurements were obtained from a nuclear magnetic resonance spectroscopy (NMR)- and a mass spectrometry (MS)-based platform. The discovery was conducted in 1726 participants of the population-based KORA-F4 study, in which the associations of the concentrations of 415 metabolites with 25(OH)D levels were assessed in linear models. The results were replicated in 6759 participants (NMR) and 609 (MS) participants, respectively, of the population-based FINRISK 1997 study. Results: Mean [standard deviation (SD)] 25(OH)D levels were 15.2 (7.5) ng/ml in KORA F4 and 13.8 (5.9) ng/ml in FINRISK 1997; 37 metabolites were associated with 25(OH) D in KORA F4 at P <0.05/415. Of these, 30 associations were replicated in FINRISK 1997 at P <0.05/37. Among these were constituents of (very) large very-low-density lipoprotein and small low-density lipoprotein subclasses and related measures like serum triglycerides as well as fatty acids and measures reflecting the degree of fatty acid saturation. The observed associations were independent of waist circumference and generally similar in abdominally obese and non-obese participants. Conclusions: Independently of abdominal obesity, higher 25(OH)D levels were associated with a metabolite profile characterized by lower concentrations of atherogenic lipids and a higher degree of fatty acid polyunsaturation. These results indicate that the relationship between vitamin D deficiency and cardiometabolic diseases is unlikely to merely reflect obesity-related pathomechanisms.
  • Pussinen, Pirkko; Paju, Susanna; Viikari, Jorma; Salminen, Aino; Taittonen, Leena; Laitinen, Tomi; Burgner, David; Kähönen, Mika; Lehtimäki, T.; Hutri-Kähönen, Niina; Raitakari, Olli; Juonala, Markus (2020)
    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.