Browsing by Subject "INTIMA-MEDIA THICKNESS"

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  • Task Force Members; ESC Comm Practice Guidelines CPG; ESC Natl Cardiac Societies; Mach, Francois; Baigent, Colin; Taskinen, Marja-Riitta (2019)
  • Sung, Yun J.; Winkler, Thomas W.; de las Fuentes, Lisa; Bentley, Amy R.; Brown, Michael R.; Kraja, Aldi T.; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K.; Li, Changwei; Feitosa, Mary F.; Kilpelainen, Tuomas O.; Richard, Melissa A.; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M.; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M.; Tayo, Bamidele O.; Warren, Helen R.; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E.; Heikkinen, Sami; Koistinen, Heikki A.; Weir, David R. (2018)
    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p <5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p <5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).
  • Pussinen, Pirkko J.; Paju, Susanna; Koponen, Jaana; Viikari, Jorma; Taittonen, Leena; Laitinen, Tomi; Burgner, David; Kähönen, Mika; Hutri-Kähönen, Niina; Raitakari, Olli; Juonala, Markus (2019)
    IMPORTANCE Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted. OBJECTIVE To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood. DESIGN, SETTING, AND PARTICIPANTS The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019. MAIN OUTCOMES AND MEASURES Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489). RESULTS This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R-2 = 0.018; P = .01), caries (R-2 = 0.022; P = .008), or both (R-2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-20.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors. CONCLUSIONS AND RELEVANCE Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.
  • Koskinen, Juhani S.; Kytö, Ville; Juonala, Markus; Viikari, Jorma S. A.; Nevalainen, Jaakko; Kähönen, Mika; Lehtimäki, Terho; Hutri-Kähönen, Nina; Laitinen, Tomi; Tossavainen, Päivi; Jokinen, Eero; Magnussen, Costan G.; Raitakari, Olli T. (2020)
    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 cutoffs in identifying children at increased risk for adulthood atherosclerosis.
  • Nuotio, Joel; Vahamurto, Lauri; Pahkala, Katja; Magnussen, Costan G.; Hutri-Kahonen, Nina; Kahonen, Mika; Laitinen, Tomi; Taittonen, Leena; Tossavainen, Paivi; Lehtimaki, Terho; Jokinen, Eero; Viikari, Jorma S. A.; Raitakari, Olli; Juonala, Markus (2019)
    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/m(2)) 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/m(2.7)) 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.
  • Chumaeva, Nadja; Hintsanen, Mirka; Hintsa, Taina; Ravaja, Niklas; Juonala, Markus; Raitakari, Olli T.; Keltikangas-Järvinen, Liisa (2010)
  • Vahamurto, Lauri; Pahkala, Katja; Magnussen, Costan G.; Mikkilä, Vera; Hutri-Kahonen, Nina; Kahonen, Mika; Laitinen, Tomi; Taittonen, Leena; Tosavainen, Paivi; Lehtimaki, Terho; Jokinen, Eero; Telama, Risto; Ronnemaa, Tapio; Viikari, Jorma; Juonala, Markus; Raitakari, Olli (2016)
    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
  • Wiegman, Albert; Gidding, Samuel S.; Watts, Gerald F.; Chapman, M. John; Ginsberg, Henry N.; Cuchel, Marina; Ose, Leiv; Averna, Maurizio; Boileau, Catherine; Boren, Jan; Bruckert, Eric; Catapano, Alberico L.; Defesche, Joep C.; Descamps, Olivier S.; Hegele, Robert A.; Hovingh, G. Kees; Humphries, Steve E.; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Masana, Luis; Nordestgaard, Borge G.; Pajukanta, Paevi; Parhofer, Klaus G.; Raal, Frederick J.; Ray, Kausik K.; Santos, Raul D.; Stalenhoef, Anton F. H.; Steinhagen-Thiessen, Elisabeth; Stroes, Erik S.; Taskinen, Marja-Riitta; Tybjaerg-Hansen, Anne; Wiklund, Olov; European Atherosclerosis Soc Conse (2015)
    Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C a parts per thousand yen5 mmol/L (190 mg/dL), or an LDL-C a parts per thousand yen4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is a parts per thousand yen3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if > 10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.
  • Bertone-Johnson, Elizabeth R.; Virtanen, Jyrki K.; Nurmi, Tarja; Niskanen, Leo; Mursu, Jaakko; Voutilainen, Sari; Ronkainen, Kimmo; Kauhanen, Jussi; Tuomainen, Tomi-Pekka (2018)
    Recent studies of perimenopausal women suggest that follicle-stimulating hormone (FSH) levels may be associated with atherosclerosis, independent of estradiol. Whether FSH is related to atherosclerosis in older postmenopausal women, who have completed the menopausal transition, remains unknown. We assessed the relationship of serum FSH and estradiol levels with carotid artery intima-media thickness (IMT) among 587 postmenopausal participants in the Kuopio Ischemic Heart Disease Risk Factor Study (Kuopio, Finland). Participants were aged 53-73 years and not using hormone therapy at baseline (1998-2001). Mean IMT was measured via high-resolution ultrasonography. We observed a significant inverse association between FSH levels and IMT. Mean IMTs among women in quartiles 1-4 of FSH were 0.94 mm, 0.91 mm, 0.87 mm, and 0.85 mm, respectively (P-trend <0.001). After adjustment for age, estradiol, testosterone, body mass index (weight (kg)/height (m)(2)), lipids, and other factors, FSH levels remained significantly associated with IMT (regression coefficients for quartiles 2-4 vs. quartile 1 were -0.038, -0.045, and -0.062, respectively; P-trend = 0.01). Findings were strongest in women aged 64-73 years (P-trend = 0.006) and did not vary by body mass index. In contrast, estradiol levels were not related to IMT. In summary, high postmenopausal FSH levels were associated with a lower atherosclerotic burden, independent of estradiol, adiposity, and other factors. Our findings warrant replication and the further exploration of potential underlying mechanisms.
  • Okser, Sebastian; Lehtimaki, Terho; Elo, Laura L.; Mononen, Nina; Peltonen, Nina; Kahonen, Mika; Juonala, Markus; Fan, Yue-Mei; Hernesniemi, Jussi A.; Laitinen, Tomi; Lyytikainen, Leo-Pekka; Rontu, Riikka; Eklund, Carita; Hutri-Kahonen, Nina; Taittonen, Leena; Hurme, Mikko; Viikari, Jorma S. A.; Raitakari, Olli T.; Aittokallio, Tero (2010)
  • Vähämurto, L.; Juonala, M.; Ruohonen, S.; Hutri-Kähönen, N.; Kähönen, M.; Laitinen, T.; Tossavainen, P.; Jokinen, E.; Viikari, J.; Raitakari, O. T.; Pahkala, K. (2018)
    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
  • Hunjadi, Monika; Lamina, Claudia; Kahler, Patrick; Bernscherer, Tamara; Viikari, Jorma; Lehtimäki, Terho; Kähönen, Mika; Hurme, Mikko; Juonala, Markus; Taittonen, Leena; Laitinen, Tomi; Jokinen, Eero; Tossavainen, Päivi; Hutri-Kähönen, Nina; Raitakari, Olli; Ritsch, Andreas (2020)
    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 H-3-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.
  • Litwin, Linda; Sundholm, Johnny K. M.; Meinilä, Jelena; Kulmala, Janne; Tammelin, Tuija H.; Rönö, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Sarkola, Taisto (2021)
    Background: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. Methods: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 +/- 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. Results: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 +/- 0.2 vs 1.2 +/- 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 +/- 0.04 vs 0.35 +/- 0.04 mm, P=0.06). Conclusion: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.
  • Laitinen, Tomi T.; Ruohonen, Saku; Juonala, Markus; Magnussen, Costan G.; Mikkila, Vera; Mikola, Hanna; Hutri-Kahonen, Nina; Laitinen, Tomi; Tossavainen, Paivi; Jokinen, Eero; Niinikoski, Harri; Jula, Antti; Viikari, Jorma S. A.; Ronnemaa, Tapani; Raitakari, Olli T.; Pahkala, Katja (2017)
    Background: Ideal cardiovascular health (CVH), defined by the American Heart Association, is associated with incident cardiovascular disease in adults. However, association of the ideal CVH in childhood with current and future cardiac structure and function has not been studied. Methods and results: The sample comprised 827 children participating in the longitudinal Special Turku Coronary Risk Factor Intervention Project (STRIP) and The Cardiovascular Risk in Young Finns Study (YFS). In STRIP, complete data on the seven ideal CVH metrics and left ventricular (LV) mass measured with echocardiography were available at the age of 15 (n= 321), 17 (n= 309) and 19 (n= 283) years. In YFS, the cohort comprised children aged 12-18 years (n = 506) with complete ideal CVH metrics data from childhood and 25 years later in adulthood, and echocardiography performed in adulthood. In STRIP, ideal CVH score was inversely associated with LV mass during childhood (P = 0.036). In YFS, childhood ideal CVH score was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume in adulthood (all P <0.01). In addition, improvement of the ideal CVH score between childhood and adulthood was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume (all P Conclusions: Childhood ideal CVH score has a long-lasting effect on cardiac structure and function, and the association is evident already in childhood. Our findings support targeting the ideal CVHmetrics as part of primordial prevention of cardiovascular diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Strawbridge, Rona J.; Silveira, Angela; den Hoed, Marcel; Gustafsson, Stefan; Luan, Jian'an; Rybin, Denis; Dupuis, Josee; Li-Gao, Ruifang; Kavousi, Maryam; Dehghan, Abbas; Haljas, Kadri; Lahti, Jari; Gadin, Jesper R.; Backlund, Alexandra; de Faire, Ulf; Gertow, Karl; Giral, Phillipe; Goel, Anuj; Humphries, Steve E.; Kurl, Sudhir; Langenberg, Claudia; Lannfelt, Lars L.; Lind, Lars; Lindgren, Cecilia C. M.; Mannarino, Elmo; Mook-Kanamori, Dennis O.; Morris, Andrew P.; de Mutsert, Renee; Rauramaa, Rainer; Saliba-Gustafsson, Peter; Sennblad, Bengt; Smit, Andries J.; Syvanen, Ann-Christine; Tremoli, Elena; Veglia, Fabrizio; Zethelius, Bjorn; Bjorck, Hanna M.; Eriksson, Johan G.; Hofman, Albert; Franco, Oscar H.; Watkins, Hugh; Jukema, J. Wouter; Florez, Jose C.; Wareham, Nicholas J.; Meigs, James B.; Ingelsson, Erik; Baldassarre, Damiano; Hamsten, Anders; IMPROVE Study Grp (2017)
    Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.
  • Cuthbertson, Daniel J.; Brown, Emily; Koskinen, Juha; Magnussen, Costan G.; Hutri-Kähönen, Nina; Sabin, Matthew; Tossavainen, Päivi; Jokinen, Eero; Laitinen, Tomi; Viikari, Jorma; Raitakari, Olli T.; Juonala, Markus (2019)
    Background & Aims We aimed to determine how childhood body mass index and metabolic health, along with the change in body mass index between childhood and adulthood, determine the risk of adult non-alcoholic fatty liver disease. Methods Data from 2020 participants aged 3-18 years at baseline, followed up 31 years later, were examined to assess the utility of four childhood metabolic phenotypes (Metabolic Groups I: normal body mass index, no metabolic disturbances; II: normal body mass index, one or more metabolic disturbances; III: overweight/obese, no metabolic disturbances; IV: overweight/obese, one or more metabolic disturbances) and four life-course adiposity phenotypes (Adiposity Group 1: normal child and adult body mass index; 2, high child, normal adult body mass index; 3, normal child body mass index, high adult body mass index; 4, high child and adult body mass index) in predicting adult non-alcoholic fatty liver disease. Results The risk for adult non-alcoholic fatty liver disease was similar across all four groups after adjustment for age, sex, lifestyle factors and adult body mass index. Risk of adult non-alcoholic fatty liver disease was not increased among individuals overweight/obese in childhood but non-obese in adulthood. In contrast, overweight or obese adults, irrespective of their youth body mass index status, had similar to eight-fold to 10-fold increased risk (P <0.001). Conclusions Childhood overweight/obesity, not metabolic health, is associated with increased risk for adult non-alcoholic fatty liver disease. However, the increased risk associated with childhood overweight/obesity can be largely removed by obtaining a normal body mass index by adulthood.
  • Sobenin, Igor A.; Salonen, Jukka T.; Zhelankin, Andrey V.; Melnichenko, Alexandra A.; Kaikkonen, Jari; Bobryshev, Yuri V.; Orekhov, Alexander N. (2014)
  • Sundholm, Johnny K. M.; Litwin, Linda; Rönö, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Sarkola, Taisto (2019)
    Background and aims: Gestational diabetes (GDM) and maternal obesity are linked to weight gain in childhood and an increased risk of cardiovascular disease later in life. We assessed the effects of GDM and maternal obesity on arterial function and morphology in relation to body anthropometrics and composition in early childhood. Methods: We assessed body size and composition, blood pressure (BP), arterial morphology and stiffness in 201 pairs of obese mothers (pre-pregnancy BMI 30.7 +/- 5.6 kg/m(2), 96 with GDM) and their children at 6.1 years (SD 0.5). Results: Child BMI (z-score 0.45 +/- 0.92; p <0.001) and common carotid intima-media thickness (IMT, z-score 0.15 +/- 0.75, p=0.003) were increased compared with a healthy Finnish reference population. No associations with maternal GDM was found. Carotid IMT and pulse wave velocity were unrelated to child sex, anthropometrics, body composition, BP, as well as maternal anthropometrics and body composition. Carotid stiffness was independently predicted by second trimester fasting glucose. Child lean body mass was the strongest independent predictor for radial (RA), and brachial artery (BA) lumen diameter (LD) and BA IMT (LD: RA: r(2)=0.068, p <0.001; BA: r(2)=0.108, p <0.001; IMT: BA: r(2)=0.161, p <0.001) and carotid LD (r(2)=0.066, p <0.001). Conclusions: Children of obese mothers have increased BMI, blood pressure and carotid IMT suggesting a transgenerational effect of maternal obesity and clustering of cardiovascular risk factors in the population. Arterial dimensions were mainly predicted by child LBM, and not associated with maternal or child adiposity, or GDM. There was a weak association with maternal gestational fasting glucose and increased carotid artery stiffness.
  • Värri, Miika; Niskanen, Leo; Tuomainen, Tomi-Pekka; Honkanen, Risto; Kröger, Heikki; Tuppurainen, Marjo T. (2020)
    Purpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association. Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (H-1) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV). Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean +/- SD: 0.033 +/- 0.0070; group II: 0.041 +/- 0.014, CI95%: 0.018.0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p>0.05). Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.