After a myocardial infarction, continuous PTH administration for several weeks had beneficial effects on survival and myocardial function (35, 36). 5.3 years, 51% female). Mean 25OHD was 54.2 25.5 nmol/L and the median PTH was 4.5 pmol/L (range 1.5C18). Main Outcomes: MRI to measure cardiac structure and function was the main outcome. Results: The lowest 25OHD category ( 25 nmol/L) compared with the highest category (75 nmol/L) was associated with a smaller left and right atrial area in unadjusted analyses; however, the associations became nonsignificant after adjustment for covariates. The highest PTH quartile compared with the lowest quartile was significantly associated with a 7.3 g (95% confidence interval 0.8, 13.8) greater left ventricular (LV) mass and a 5.1% (?9.1, ?1.1) lower LV ejection fraction compared with the lowest PTH quartile in the fully adjusted model. Conclusions: Serum 25OHD concentrations were not associated with MRI measures in an older white population. Higher PTH concentrations were associated with greater LV mass and lower systolic function and may point to a potential role for PTH as a determinant of cardiac remodeling. Emerging evidence suggests a role for disturbances in mineral metabolism Halofuginone in the development of cardiac diseases. Specifically, low circulating vitamin D and excess PTH have been associated with clinical cardiovascular disease (CVD) outcomes, including incident hypertension, myocardial hypertrophy, heart failure, and CVD death (1C6). Multiple mechanisms have been proposed to explain these observations. In an animal model, targeted deletion of the vitamin D receptor within cardiomyocytes directly led to hypertension, increased myocyte size, and greater overall left ventricular (LV) mass (7). Furthermore, PTH excess increased intracellular calcium content, protein synthesis, and cardiomyocyte mass (8). In cardiac patients, an inverse association between 25-hydroxyvitamin D (25OHD) and overstimulation of the renin-angiotensin system was observed (9). This implies that 25OHD might have antihypertensive and tissue-protective properties attributed to the inhibition of renin synthesis. Lower vitamin D and PTH excess could potentially increase blood pressure (BP) and promote myocardial hypertrophy and thereby influence cardiac remodeling and, in turn, explain CVD (1, 10) or heart failure risk (1, 11C13), although not observed consistently (14, 15). More human data are needed to elucidate the relationship between vitamin D, PTH, and cardiac remodeling to clarify Halofuginone their role in cardiac diseases. Several studies investigated vitamin D and/or PTH in relation to cardiac structure and function by echocardiography (2, 11, 16C20). However, magnetic resonance imaging (MRI) assesses cardiac structure and function better than echocardiography and is now regarded as the reference method (21). Cardiac MRI is usually more sensitive than prior methods and tissue characterization is relevant because heart function decline may culminate in cardiac diseases (22). In this study, we tested the hypothesis that low 25OHD, an established marker of vitamin D deficiency, and high PTH concentrations are associated with unfavorable MRI measures of cardiac structure and function in older white men and women in ICELAND-MI, a substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). Materials and Methods Design and participants ICELAND-MI is an older-aged, community-dwelling cohort of 992 individuals recruited between January 2004 and January 2007 from the AGES-Reykjavik Study, which is a randomly selected cohort of 5764 older men and women born between 1907 and 1935 and followed up since 1967 by the Icelandic Heart Association (23). Participants in AGES-Reykjavik were eligible to participate in ICELAND-MI if they could safely receive MRI scans (ie, no implanted device or severe kidney disease) and provided written informed consent as described previously (24). A total of 992 participants were enrolled for MRI measurements: 702 randomly selected participants and 290 participants with type 2 diabetes. Twenty-three participants did not complete MRI measurements and Rabbit polyclonal to HAtag were excluded. None of the participants used lithium, which may alter calcium metabolism. The analytical sample of this study included 969 participants who successfully underwent MRI and had serum 25OHD measurements. Serum PTH was measured in a subsample and available for 203 participants (23). The study was approved by the Icelandic National Halofuginone Bioethics Committee, the Icelandic Data Protection Authority, and the Institutional Review Board of the National Institute on Aging (Bethesda, Maryland). Serum 25OHD and PTH measurements Fasting blood samples were drawn between 8:00 am and 12:00 pm and processed on-site at the Icelandic Heart Association where its Clinical Biochemistry Laboratory Holtasmra stored serum samples at ?70C. The laboratory performed 25OHD measurements in batch using the Liaison chemiluminescence immunoassay (DiaSorin Inc, Stillwater, Minnesota). The interassay coefficient of variation was less than 6.5% when using a frozen serum pool as control sample and was less than 12.7% when using Liaison quality controls. Intact PTH was measured using electrochemiluminescence technology from Cobas-Roche.Additionally, we investigated whether the association between serum 25OHD and PTH in relation to cardiac MRI measures was influenced by factors that reflect potential pathways or factors that could mediate these association. became nonsignificant after adjustment for covariates. The highest PTH quartile compared with the lowest quartile was significantly associated with a 7.3 g (95% confidence interval 0.8, 13.8) greater left ventricular (LV) mass and a 5.1% (?9.1, ?1.1) lower Halofuginone LV ejection fraction compared with the lowest PTH quartile in the fully adjusted model. Conclusions: Serum 25OHD concentrations were not associated with MRI measures in an older white population. Higher PTH concentrations were associated with greater LV mass and lower systolic function and may point to a potential role for PTH as a determinant of cardiac remodeling. Emerging evidence suggests a role for disturbances in mineral metabolism in the introduction of cardiac illnesses. Particularly, low circulating supplement D and excessive PTH have already been associated with medical coronary disease (CVD) results, including event hypertension, myocardial hypertrophy, center failing, and CVD loss of Halofuginone life (1C6). Multiple systems have been suggested to describe these observations. Within an pet model, targeted deletion from the supplement D receptor within cardiomyocytes straight resulted in hypertension, improved myocyte size, and higher overall remaining ventricular (LV) mass (7). Furthermore, PTH excessive increased intracellular calcium mineral content, proteins synthesis, and cardiomyocyte mass (8). In cardiac individuals, an inverse association between 25-hydroxyvitamin D (25OHD) and overstimulation from the renin-angiotensin program was noticed (9). Therefore that 25OHD may have antihypertensive and tissue-protective properties related to the inhibition of renin synthesis. Decrease supplement D and PTH excessive could potentially boost blood circulation pressure (BP) and promote myocardial hypertrophy and therefore influence cardiac redesigning and, subsequently, clarify CVD (1, 10) or center failing risk (1, 11C13), while not noticed regularly (14, 15). Even more human being data are had a need to elucidate the partnership between supplement D, PTH, and cardiac redesigning to clarify their part in cardiac illnesses. Several studies looked into supplement D and/or PTH with regards to cardiac framework and function by echocardiography (2, 11, 16C20). Nevertheless, magnetic resonance imaging (MRI) assesses cardiac framework and work better than echocardiography and is currently thought to be the reference technique (21). Cardiac MRI can be more delicate than prior strategies and cells characterization is pertinent because center function decrease may culminate in cardiac illnesses (22). With this research, we examined the hypothesis that low 25OHD, a recognised marker of supplement D insufficiency, and high PTH concentrations are connected with unfavorable MRI actions of cardiac framework and function in old white women and men in ICELAND-MI, a substudy of this, Gene/Environment Susceptibility-Reykjavik Research (AGES-Reykjavik). Components and Methods Style and individuals ICELAND-MI can be an older-aged, community-dwelling cohort of 992 people recruited between January 2004 and January 2007 through the AGES-Reykjavik Study, which really is a arbitrarily chosen cohort of 5764 old women and men created between 1907 and 1935 and adopted up since 1967 from the Icelandic Center Association (23). Individuals in AGES-Reykjavik had been eligible to take part in ICELAND-MI if indeed they could securely receive MRI scans (ie, no implanted gadget or serious kidney disease) and offered written educated consent as referred to previously (24). A complete of 992 individuals had been enrolled for MRI measurements: 702 arbitrarily selected individuals and 290 individuals with type 2 diabetes. Twenty-three individuals did not full MRI measurements and had been excluded. None from the individuals used lithium, which might alter calcium rate of metabolism. The analytical test of this research included 969 individuals who effectively underwent MRI and got serum 25OHD measurements. Serum PTH was assessed inside a subsample and designed for 203 individuals (23). The analysis was authorized by the Icelandic Country wide Bioethics Committee, the Icelandic Data Safety Authority, as well as the.