The Association Between Vitamin D and Inflammation with the 6-Minute Walk and Frailty in Patients with Heart Failure

Department of Family Medicine, Case Western University Hospital, Cleveland, Ohio 44106, USA.
Journal of the American Geriatrics Society (Impact Factor: 4.57). 03/2008; 56(3):454-61. DOI: 10.1111/j.1532-5415.2007.01601.x
Source: PubMed


To identify relationships between anabolic hormones, inflammatory markers, and physical function.
Outpatient university heart failure program in Connecticut.
Sixty patients with an ejection fraction of 40% or less.
The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Linear and ordinal logistic regression analyses were performed for the physical measures.
Forty-three men (mean age 77 +/- 9) and 17 women (mean age 78 +/- 12) participated. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) (all P<.05). Percentage of free testosterone, DHEAS alone, and N-terminal pro-brain natriuretic peptide (NTpro-BNP) did not correlate with 6-minute walk distance. Higher frailty phenotype score (more frail) was correlated with higher high-sensitivity CRP, higher IL6, and lower 25OHD levels (all P<.05). Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25OHD, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed age, sex, 25OHD and hsCRP to be significant (coefficient of determination=53.5%). Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that age, 25OHD, and hsCRP also predicted frailty status.
Twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

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    • "Exercise intolerance is directly related to exercise dyspnea and early fatigue, which can be the major cause of low levels of physical activity in this population, and a vicious cycle clearly ensues. Vitamin D deficiency is positively correlated with worse aerobic capacity in heart failure [43, 44] and in healthy adults, an association that is stronger among those who reported the lowest level of physical activity [45]. We were able to show, for the first time, that vitamin D deficiency associated with diabetes results in higher impact on physical function than in each isolated condition, as evaluated by the 6 MWT. "
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    ABSTRACT: Vitamin D deficiency is frequent among patients with heart failure (HF) and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT), handgrip strength, physical activity level (IPAQ), and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient) and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, n = 25), vitamin sufficient, diabetes (DS-DM, n = 18), vitamin deficient, no diabetes (DD-C, n = 63), and vitamin deficient, diabetes (DD-DM, n = 40). Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups (P = 0.26). DS-C covered higher distances in the 6 MWT (392 ± 60 m) versus DD-DM (309 ± 116 m); P = 0.024. Handgrip strength was similar among groups but tended to lower levels in DD-DM (P = 0.074) even after being adjusted to physical activity (P = 0.069). Vitamin D deficiency can influence physical function in HF diabetic patients.
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    • "n = 1332) [33]. Using a different definition of frailty, Boxer et al. [34] showed that 25% of elderly patients with chronic heart failure were frail. Tjam et al. [35] showed that frailty was more predictive of mortality than New York Heart Association (NYHA) class. "
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    ABSTRACT: Frailty is a geriatric syndrome of impaired resistance to stressors due to a decline in physiologic reserve. Frailty and cardiovascular disease (CVD) share a common biological pathway, and CVD may accelerate the development of frailty. Frailty is identified in 25% to 50% of patients with CVD, depending on the frailty scale used and the population studied. Frail patients with CVD, especially those undergoing invasive procedures or suffering from coronary artery disease and heart failure, are more likely to suffer adverse outcomes as compared to their non-frail counterparts. Five-meter gait speed is a simple and effective way of objectively measuring frailty in patients with CVD and should be incorporated in risk assessment.
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    ABSTRACT: Riassunto. Il crescente diffuso spostamento degli esseri umani da un ambiente naturale all'aria aperta verso uno sti-le di vita al chiuso e sedentario, insieme con le raccoman-dazioni di evitare un'esposizione diretta al sole per il rischio di cancro cutaneo, ha indotto una globale carenza di vita-mina D. Tradizionalmente, la vitamina D è stata associata prioritaria-mente alla salute ossea. Tuttavia, è divenuto evidente che uno stato adeguato di vitamina D è importante per la fun-zione ottimale di molti organi e tessuti corporei, compreso il sistema cardiovascolare. L'insufficienza di vitamina D sem-bra predisporre a ipertensione, diabete e sindrome meta-bolica, ipertrofia ventricolare sinistra, scompenso cardiaco, infiammazione vascolare cronica. Attraverso i trial rando-mizzati in corso si potrà meglio investigare la relazione tra livelli basali di vitamina D, dosi necessarie di supplementa-zioni di vitamina D ed eventi cardiovascolari; tuttavia, un'evi-denza sempre crescente suggerisce che correggere una in-sufficienza di vitamina D, provvedimento semplice, ben tol-lerato e molto economico, agisce favorevolmente sulla mor-bilità e mortalità delle malattie cardiovascolari, oltre a pre-venire le più comuni malattie cronico-degenerative. Parole chiave. Malattie cardiovascolari, vitamina D. Summary. The relationship between the vitamin D insuffi-ciency and the development of cardiovascular disease. The increasing worldwide displacement from the natural out-door environment of human beings to an indoor sedentary lifestyle, along with the recommendation to avoid any direct sun exposure because of the risk of skin cancer, has resulted in a global pandemic of vitamin D insufficiency. Traditional-ly, vitamin D has been associated primarily with bone health. However, it has become evident that adequate vitamin D sta-tus is important for optimal function of many organs and tis-sues throughout the body, including the cardiovascular sys-tem. Vitamin D insufficiency seems to predispose to hyper-tension, diabetes and the metabolic syndrome, left ventricu-lar hypertrophy, heart failure, and chronic vascular inflam-mation. The relationship between baseline vitamin D status, dose of vitamin D supplements, and cardiovascular events remains to be investigated by ongoing randomized trials; however increasing evidence suggests that the provision of a simple, well-tolerated, and inexpensive correction of vita-min D insufficiency favourably affects the morbility and mor-tality of cardiovascular disease along with the prevention of the most common chronic degenerative diseases.
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