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| 4. |
- Nielson, Carrie M., et al.
(författare)
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Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
- 2016
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431. ; 31:12, s. 2085-2097
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (β=0.22, p=1.9×10-8) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (β=0.09, p=1.2×10-10) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4×10-4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β=0.12, FDR p=1.7×10-3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence.
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| 5. |
- Chen, Hao Yu, et al.
(författare)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 6. |
- Tang, W. H. Wilson, et al.
(författare)
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Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations
- 2024
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Ingår i: CIRCULATION-HEART FAILURE. - 1941-3289 .- 1941-3297. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, gamma-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). METHODS:We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. RESULTS:In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. CONCLUSIONS:In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF.
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| 7. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 8. |
- Malhotra, Rajeev, et al.
(författare)
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HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:11, s. 1580-
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Tidskriftsartikel (refereegranskat)abstract
- Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10−8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein–deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.
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| 9. |
- Nicoll, Rachel, et al.
(författare)
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The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients : Euro-CCAD study
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 207, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. Methods and Results: We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.50 of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B = 1.07) followed by diabetes mellitus (B = 0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B = 1.25), followed by male gender (B = 0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC 0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC 0.81). Conclusion: In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.
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| 10. |
- Nielsen, Rikke V., et al.
(författare)
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Personalized intervention based on early detection of atherosclerosis : JACC state-of-the-art review
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:21, s. 2112-2127
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Forskningsöversikt (refereegranskat)abstract
- Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required—moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health.
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| 11. |
- Thanassoulis, George, et al.
(författare)
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Genetic Associations with Valvular Calcification and Aortic Stenosis
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 368:6, s. 503-512
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Tidskriftsartikel (refereegranskat)abstract
- Background Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. Methods We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. Results One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P = 9.0x10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P = 1.5x10(-8) and P = 1.8x10(-8), respectively), but the findings were not replicated consistently. Conclusions Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 12. |
- Henein, Michael, et al.
(författare)
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European Calcific Coronary Artery Disease (Euro-CCAD) study : the additional value of coronary calcification, to angiography, in investigating angina patients
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:Supplement: 1, s. 177-177
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.
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| 13. |
- Henein, Michael Y., et al.
(författare)
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European Calcific Coronary Artery Disease (Euro-CCAD) study : the relationship between coronary calcification and flow limiting lesion in symptomatic patients
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 34:Supplement: 1, s. 723-723
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.
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| 16. |
- Nicoll, Rachel, et al.
(författare)
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Diabetes and male gender are key risk factor predictors of CAC extent : a Euro-CCAD study
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Although much has been written about the risk factor predictors of CAC extent, few studies have been carried out on symptomatic patients. Similarly, no study has directly compared predictors of CAC extent and zero CAC.Methods: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring. Results: Among all patients, male gender (β = 1.36, p<0.001) and diabetes (β = 0.47, p<0.001) were the most important risk factors of CAC extent, with age, diabetes (DM), obesity, family history of CAD and number of risk factors also being predictive. Among patients with CAC, DM, hypertension (HT) and dyslipidaemia (DL) were predictors of an increasing CAC score in males and females, with DM being the strongest (p<0.001 for both). These results were echoed in quantile regression, where DM was consistently the most important predictor of CAC extent in every quantile in both males and females. HT and DL were also predictive but to a lesser extent, with HT being predictive in the high CAC quantiles and DL in the low CAC quantiles. Conclusion: In addition to male gender, DM is the most important predictor of CAC extent in both genders.
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| 18. |
- Nicoll, Rachel, et al.
(författare)
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Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients : a Euro-CCAD study
- 2016
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 252, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) presence in symptomatic patients is unclear.Methods: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring. Results: The prevalence of CAC among females was lower than among males in all age groups. Using multivariate logistic regression, age, dyslipidaemia, hypertension, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (β = 0.64 and 0.63 respectively) in males and diabetes (β = 1.08) followed by smoking (β = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70 years. However, in patients aged >70, only dyslipidaemia predicted CAC presence in males and only smoking and diabetes were predictive in females. Conclusion: In symptomatic patients, there are significant differences in the ability of conventional risk factors to predict CAC presence between genders and between patients aged <70 and ≥70, indicating the important role of age in predicting CAC presence.
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| 20. |
- Rhee, CM, et al.
(författare)
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Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients
- 2022
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Ingår i: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 12:3, s. 106-116
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. <b><i>Methods:</i></b> In secondary analyses of patients from the <i>Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients</i> trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm<sup>3</sup> and >100 Houndsfield Units, respectively) using multivariable logistic regression. <b><i>Results:</i></b> Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. <b><i>Conclusions:</i></b> In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.
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| 21. |
- Rhee, CM, et al.
(författare)
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Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients
- 2022
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Ingår i: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 12:3, s. 106-116
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. <b><i>Methods:</i></b> In secondary analyses of patients from the <i>Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients</i> trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm<sup>3</sup> and >100 Houndsfield Units, respectively) using multivariable logistic regression. <b><i>Results:</i></b> Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. <b><i>Conclusions:</i></b> In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.
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