Browsing by Subject "ATHEROSCLEROSIS RISK"

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  • Liljestrand, J. M.; Salminen, A.; Lahdentausta, L.; Paju, S.; Mäntylä, P.; Buhlin, K.; Tjäderhane, L.; Sinisalo, J.; Pussinen, P. J. (2021)
  • FinnDiane Study Grp; Eriksson, Marika; Summanen, Paula; Gordin, Daniel; Forsblom, Carol; Shams, Sara; Liebkind, Ron; Tatlisumak, Turgut; Putaala, Jukka; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2021)
    Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.
  • Louca, Panayiotis; Nogal, Ana; Moskal, Aurelie; Goulding, Neil J.; Shipley, Martin J.; Alkis, Taryn; Lindbohm, Joni; Hu, Jie; Kifer, Domagoj; Wang, Ni; Chawes, Bo; Rexrode, Kathryn M.; Ben-Shlomo, Yoav; Kivimaki, Mika; Murphy, Rachel A.; Yu, Bing; Gunter, Marc J.; Suhre, Karsten; Lawlor, Deborah A.; Mangino, Massimo; Menni, Cristina (2022)
    Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813). Metabolites were aligned and inverse normalised to allow intra-platform comparison. Logistic models adjusting for covariates were performed in each cohort and results were combined using random-effect inverse-variance meta-analyses adjusting for multiple testing. We further conducted canonical pathway analysis to investigate the pathways underlying the hypertension-associated metabolites. In 12,479 hypertensive cases and 31,827 controls without renal impairment, we identified 38 metabolites, associated with hypertension after adjusting for age, sex, body mass index, ethnicity, and multiple testing. Of these, 32 metabolite associations, predominantly lipid (steroids and fatty acyls) and organic acids (amino-, hydroxy-, and keto-acids) remained after further adjusting for comorbidities and dietary intake. Among the identified metabolites, 5 were novel, including 2 bile acids, 2 glycerophospholipids, and ketoleucine. Pathway analysis further implicates the role of the amino-acids, serine/glycine, and bile acids in hypertension regulation. In the largest cross-sectional hypertension-metabolomics study to date, we identify 32 circulating metabolites (of which 5 novel and 27 confirmed) that are potentially actionable targets for intervention. Further in-vivo studies are needed to identify their specific role in the aetiology or progression of hypertension.
  • Eranti, Antti; Kerola, Tuomas; Aro, Aapo L.; Tikkanen, Jani T.; Rissanen, Harri A.; Anttonen, Olli; Junttila, M. Juhani; Knekt, Paul; Huikuri, Heikki V. (2016)
    Background: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. Methods: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose = 9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). Results: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p <0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects. Conclusions: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of nonfatal cardiac event during the follow-up.
  • Pirinen, Jani; Eranti, Antti; Knekt, Paul; Lehto, Mika; Martinez-Majander, Nicolas; Aro, Aapo L.; Rissanen, Harri; Heliövaara, Markku; Kaste, Markku; Tatlisumak, Turgut; Huikuri, Heikki; Putaala, Jukka (2017)
    Introduction: Certain electrocardiographic (ECG) abnormalities are associated with ischemic stroke (IS), especially cardioembolic subtype. Besides atrial fibrillation, markers of left ventricular hypertrophy (LVH) or atrial pathology also reflect elevated risk. We studied the association of ECG markers with IS in young adults. Methods: We performed a case-control study including 567 consecutive IS patients aged 15-49 years (inclusion period: 1994-2007) and one or two age-and sex-matched control subjects enrolled during 1978-1980 (n = 1033), and investigated also the stroke aetiologic subgroups. We studied ECGs of all participants for markers of atrial abnormality, i.e. P-terminal force (PTF) on lead V1, interatrial blocks (IAB; P-wave duration >= 110ms), and LVH. Conditional logistic regression analyses were used. Results: IAB (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.16-2.13) and PTF combined with LVH (HR: 6.83, 95% CI: 1.65-28.31), were independently associated with IS. LVH, abnormal P-wave (HR: 6.87, 95% CI: 1.97-135.29), PTF, IAB, and combinations of these P-wave abnormalities with LVH - were associated with cardioembolic subtype. Abnormal P-wave and IAB were associated with cryptogenic stroke subtype. In unadjusted analysis, LVH was associated with small-vessel disease subtype. Conclusion: P-wave abnormalities on ECG were associated with cardioembolic but also with a cryptogenic subtype of IS.
  • Ikram, M. Kamran; Xueling, Sim; Jensen, Richard A.; Cotch, Mary Frances; Hewitt, Alex W.; Ikram, M. Arfan; Wang, Jie Jin; Klein, Ronald; Klein, Barbara E. K.; Breteler, Monique M. B.; Cheung, Ning; Liew, Gerald; Mitchell, Paul; Uitterlinden, Andre G.; Rivadeneira, Fernando; Hofman, Albert; de Jong, Paulus T. V. M.; van Duijn, Cornelia M.; Kao, Linda; Cheng, Ching-Yu; Smith, Albert Vernon; Glazer, Nicole L.; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M.; Jonasson, Fridbert; Eiriksdottir, Gudny; Aspelund, Thor; Harris, Tamara B.; Launer, Lenore J.; Taylor, Kent D.; Li, Xiaohui; Iyengar, Sudha K.; Xi, Quansheng; Sivakumaran, Theru A.; Mackey, David A.; MacGregor, Stuart; Martin, Nicholas G.; Young, Terri L.; Bis, Josh C.; Wiggins, Kerri L.; Heckbert, Susan R.; Hammond, Christopher J.; Andrew, Toby; Fahy, Samantha; Attia, John; Holliday, Elizabeth G.; Scott, Rodney J.; Islam, F. M. Amirul; Tuomilehto, Jaakko; Global BPgen Consortium (2010)
  • Seidelmann, Sara B.; Feofanova, Elena; Yu, Bing; Franceschini, Nora; Claggett, Brian; Kuokkanen, Mikko; Puolijoki, Hannu; Ebeling, Tapani; Perola, Markus; Salomaa, Veikko; Shah, Amil; Coresh, Josef; Selvin, Elizabeth; MacRae, Calum A.; Cheng, Susan; Boerwinkle, Eric; Solomon, Scott D. (2018)
    BACKGROUND Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated. In the general population, variants related to intestinal glucose absorption remain uncharacterized. OBJECTIVES The goat of this study was to identify functional SGLT1 gene variants and characterize their clinical consequences. METHODS Whole exome sequencing was performed in the ARIC (Atherosclerosis Risk in Communities) study participants enrolled from 4 U.S. communities. The association of functional, nonsynonymous substitutions in SGLT1 with 2-h oral glucose tolerance test results was determined. Variants related to impaired glucose tolerance were studied, and Mendelian randomization analysis of cardiometabotic outcomes was performed. RESULTS Among 5,687 European-American subjects (mean age 54 +/- 6 years; 47% mate), those who carried a haplotype of 3 missense mutations (frequency of 6.7%)-Asn51Ser, Ala411Thr, and His615Gln-had lower 2-h glucose and odds of impaired glucose tolerance than noncarriers (beta-coefficient: -8.0; 95% confidence interval [CI]: -12.7 to -3.3; OR: 0.71; 95% CI: 0.59 to 0.86, respectively). The association of the haplotype with oral glucose tolerance test results was consistent in a replication sample of 2,791 African-American subjects (beta = -16.3; 95% CI: -36.6 to 4.1; OR: 0.39; 95% CI: 0.17 to 0.91) and an external European-Finnish population sample of 6,784 subjects (beta = -3.2; 95% CI: -6.4 to 0.02; OR: 0.81; 95% CI: 0.68 to 0.98). Using a Mendelian randomization approach in the index cohort, the estimated 25-year effect of a reduction of 20 mg/dl in 2-h glucose via SGLT1 inhibition would be reduced prevalent obesity (OR: 0.43; 95% CI: 0.23 to 0.63), incident diabetes (hazard ratio [HR]: 0.58; 95% CI: 0.35 to 0.81), heart failure (HR: 0.53; 95% CI: 0.24 to 0.83), and death (HR: 0.66; 95% CI: 0.42 to 0.90). CONCLUSIONS Functionally damaging missense variants in SGLT1 protect from diet-induced hyperglycemia in multiple populations. Reduced intestinal glucose uptake may protect from long-term cardiometabolic outcomes, providing support for therapies that target SGLT1 function to prevent and treat metabolic conditions. (C) 2018 Published by Elsevier on behalf of the American College of Cardiology Foundation.
  • Lehtonen, Arttu O.; Langen, Ville L.; Puukka, Pauli J.; Kahonen, Mika; Nieminen, Markku S.; Jula, Antti M.; Niiranen, Teemu J. (2017)
    Background: Scant data exist on incidence rates, correlates, and prognosis of electrocardiographic P-wave abnormalities in the general population. Methods: We recorded ECG and measured conventional cardiovascular risk factors in 5667 Finns who were followed up for incident atrial fibrillation (AF). We obtained repeat ECGs from 3089 individuals I I years later. Results: The incidence rates of prolonged P-wave duration, abnormal P terminal force (PTF), left P-wave axis deviation, and right P-wave axis deviation were 16.0%, 7.4%, 3.4%, and 2.2%, respectively. Older age and higher BMI were associated with incident prolonged P-wave duration and abnormal PTF (P Conclusions: Modifiable risk factors associate with P-wave abnormalities that are common and may represent intermediate steps of atrial cardiomyopathy on a pathway leading to AF. (C) 2017 Elsevier Inc. All rights reserved.