Journal of Cardiovascular Nursing
Vol. 00, No. 0, pp 00Y00 x Copyright B 2016 Wolters Kluwer Health, Inc. All rights reserved.
Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure An Observational Study Nicholas A. McKeag, MB, BCh, PhD; Michelle C. McKinley, PhD; Mark T. Harbinson, MD; Ann McGinty, PhD; Charlotte E. Neville, PhD; Jayne V. Woodside, PhD; Pascal P. McKeown, MD Background: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status. Objective: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure. Methods: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion. Results: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration G50 nmol/L) was observed in 75.6% of patients. Conclusions: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs. KEY WORDS:
heart failure, macronutrients, micronutrients, nutrition
H
eart failure is a syndrome comprising symptoms such as breathlessness, alongside signs of fluid retention such as pulmonary congestion or ankle swelling, resulting from an abnormality of cardiac structure
Nicholas A. McKeag, MB, BCh, PhD Clinical Research Fellow, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom.
Michelle C. McKinley, PhD Senior Lecturer, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Mark T. Harbinson, MD Senior Lecturer, Centre for Medical Education, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom.
Ann McGinty, PhD Lecturer, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Charlotte E. Neville, PhD Research Fellow, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
or function.1 Poor nutritional status is associated with mortality in patients with heart failure.2 Micronutrients (defined as substances needed only in small amounts for normal body function3) may play an important role
Jayne V. Woodside, PhD Professor, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Pascal P. McKeown, MD Professor, Centre for Medical Education, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom. This work was supported by a Northern Ireland Health & Social Care R&D Doctoral Fellowship Award and a Northern Ireland Chest Heart & Stroke Association Grant. Nicholas A. McKeag: honorarium from Biotronik, Laboratoires Servier, Medtronic, Menarini Pharma UK, Sorin Group, and St Jude Medical. The other authors have no conflicts of interest to disclose.
Correspondence Nicholas A. McKeag, MB, BCh, PhD, Centre for Public Health, Queen’s University Belfast, Institute of Clinical Sciences Block B, Grosvenor Road, Belfast BT12 6BJ, United Kingdom ([email protected]). DOI: 10.1097/JCN.0000000000000322
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2 Journal of Cardiovascular Nursing x Month 2016 in heart failure. Observational studies suggest that patients with heart failure may have a tendency to reduced or suboptimal status of a number of micronutrients, including vitamin A, vitamin C, thiamine, vitamin B12, vitamin D, selenium, copper, and zinc.4 Micronutrient deficiency in patients with heart failure may be associated with an adverse prognosis. A number of large observational studies have suggested that vitamin D deficiency or suboptimal status is associated with mortality in patients with heart failure.5Y8 Iron deficiency is also common in patients with heart failure, with a prevalence of up to 50%, and is associated with an increased risk of death.9 In a large intervention study involving patients with heart failure and evidence of iron deficiency, treatment with intravenous iron was associated with an improvement in symptoms, functional capacity, and quality of life.10 The mechanism for suboptimal micronutrient status in patients with heart failure is not clear. A small number of observational studies, using varying methods of dietary assessment, have suggested that patients with heart failure have reduced dietary intake of a wide range of micronutrients.11Y18 Very few of these studies investigated dietary micronutrient status alongside micronutrient intake. The aims of this study were to assess dietary micronutrient intake and micronutrient status in patients with chronic stable heart failure and to examine differences in dietary intake across 3 vitamin D status subgroups. A wide-ranging group of micronutrients was chosen for dietary intake assessment because previous studies have suggested reduced intake of a large number of different micronutrients. With respect to micronutrient status, the micronutrients assessed were chosen because of previous data suggesting suboptimal status in patients with heart failure (particularly vitamin D and ferritin9,19). Study Overview and Participants This was an observational study performed at a single tertiary referral hospital in Belfast, Northern Ireland. The study was approved by the Office for Research Ethics Committee Northern Ireland. All patients provided written informed consent before participation. The study is based on data collected at baseline from patients who participated in the Micronutrient Supplementation in Patients With Heart Failure study, a clinical trial conducted to investigate the effect of multiple micronutrient supplementation in patients with chronic stable heart failure.20 Patients were invited to take part in the study at hospital-based heart failure outpatient clinics in Northern Ireland. Inclusion and exclusion criteria are listed in Table 1. Patients receiving a multivitamin or mineral supplement or vitamin DYcontaining fish oil were excluded from participating in this study.
Baseline Characteristics and Dietary Intake Assessment The baseline characteristics of patients taking part in the study were collected by a trained member of the research team (doctor or registered nurse) using a standardized questionnaire. Patients were asked to complete a modified version of the European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ), similar to that used in the US Nurses’ Health Study.21,22 This semiquantitative FFQ, including 130 food items, was used to assess food and nutrient intake during the previous year. The FFQ was adapted to include foods that are commonly consumed within the United Kingdom and Northern Ireland and has been validated within the UK population.23 For each food item, participants indicated their usual consumption over the previous year from 9 frequency categories (never/less than once a month, 1Y3 per month, once a week, 2Y4 per week, 5Y6 per week, once a day, 2Y3 per day, 4Y5 per day, or more than 6 per day). The FFQ is semiquantitative and so does not include specific questions on portion size, but rather, it asks participants to estimate their intake in terms of how many medium portions were consumed; what is meant by ‘‘medium’’ is described in the FFQ according to natural (eg, slice of bread) or household (eg, glass, cup, or spoon) units. An explanation of how to complete the questionnaire was provided by a trained member of the research team. Patients were asked to indicate how often on average they had eaten the specified amount of each food item during the past year. A completed example page was provided for review. The FFQ was completed by the patient in a private research office with a trained member of the research team present to answer any questions. It took patients approximately 20 to 30 minutes to complete the FFQ. This FFQ has been compared with 24-hour recalls and 24-hour urinary nitrogen excretion in subjects from the Netherlands21,22 and France24 and 4-day weighted records and 24-hour urinary nitrogen excretion in subjects from the United Kingdom.25 Overall, these studies indicate good reproducibility and modest to good validity. Nutrient intake was calculated using the method described by Bingham et al.25 Briefly, the selected frequency of consumption for each food item was multiplied by a standard portion weight to obtain a daily intake in grams per day. The weights of natural or household units were derived from those used in previous dietary surveys and from published values.25,26 Mean energy and nutrient intakes for foods were then calculated using a computerized food analysis database (Weighed Intake Software Program; Tinuviel Software, Warrington, United Kingdom) based on UK food composition tables.
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Micronutrient Intake and Status in Heart Failure Patients 3 TABLE 1 Inclusion and Exclusion Criteria in the Micronutrient Supplementation in Patients With Heart Failure Study20 Inclusion criteria Age 18Y80 y New York Heart Association symptomatic class II or III On best known medical treatment (on or tried on and unable to tolerate an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a "-blocker) Stable for 6 wks (no acute exacerbations of heart failure and no changes to heart failure treatment) Left ventricular ejection fraction e45% (measured by echocardiography, contrast ventriculography, cardiovascular magnetic resonance imaging or radionuclide ventriculography) Exclusion criteria Alcohol intake > 40 units (320 g) per week Severe renal impairment (glomerular filtration rate G 30 mL/min) Severe hepatic dysfunction (known significant liver disease or serum transaminases greater than 3 times the upper limit of normal) Atrial fibrillation in the absence of a pacemaker Frequent ventricular ectopics On waiting list for cardiac transplantation Uncontrolled diabetes mellitus Inability to give informed consent Estimated life span G12 mo Already taking a multivitamin or mineral supplement or vitamin DYcontaining fish oil Woman of child-bearing potential Personal history of renal stones, hypercalcemia, sarcoidosis, hemochromatosis, or lactose intolerance
Micronutrient intake was compared with the Endocrine Society Clinical Practice Guideline for vitamin D27 and UK dietary reference values for all other micronutrients.28 The UK dietary reference values are reported in the form of a reference nutrient intake (RNI) and a lower reference intake (LRNI). The RNI for a nutrient represents the amount of that nutrient that is sufficient or more than sufficient for approximately 97.5% of a group. Intakes above this limit are almost certainly adequate for most individuals. The LRNI for a nutrient represents the amount of that nutrient that is sufficient or more than sufficient for only a small proportion of a group (2.5% of people). Intakes below this limit are almost certainly inadequate for most individuals.25 Measurement of Micronutrient Status Serum ferritin concentration was measured using an electrochemiluminescence immunoassay (Roche Diagnostics, Burgess Hill, United Kingdom). Serum concentrations of vitamin B12 and folate were measured using chemiluminescent microparticle assays (Roche Diagnostics). Serum vitamin D concentration was measured using ultra performance liquid chromatography followed by tandem mass spectrometry13 (Waters Corporation, Milford, Massachusetts). This method measures both 25-hydroxy-vitamin D2 and 25-hydroxy-vitamin D3, and results are presented as total 25-hydroxy-vitamin D. Plasma vitamin B6 concentration (pyridoxal phosphate) was measured using high-performance liquid chromatography with fluorescence detection (Chromsystems Instruments & Chemicals GmbH, Gra¨felfing, Germany). All assays were closely monitored for performance, and all interassay and intra-assay coefficients of variation
were less than 15%. Fasting blood samples were drawn at the time of FFQ completion. Statistics Results are presented as mean T SD for continuous variables and number (percentage) for categorical variables. Mean intake in grams of 5 food groups (fish and fish dishes, meat and meat products, cereals and cereal products, eggs and egg dishes, and fat spreads) that are recognized as the main sources of vitamin D in the diet29 was examined across 3 vitamin D status groups (plasma total 25-hydroxy-vitamin D concentration G25 nmol/L, 25Y50 nmol/L, and >50 nmol/L) using analysis of variance. All analyses were performed with IBM SPSS Statistics version 20 (IBM Corporation, New York, New York).
Results Seventy-nine patients were recruited. Baseline characteristics are presented in Table 2. The mean age of participants was 64.5 years and 19.0% were women. Patients were, on average, overweight, with a mean body mass index of 29.7 kg/m2. Ischemic heart disease was twice as common as nonYischemic heart disease with respect to etiology of heart failure. Most (79.7%) patients were New York Heart Association functional class II. Most patients were receiving current best drug therapy for heart failure, with nearly all receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (97.5%) and "-blocker (93.7%) and 51.9% receiving a mineralocorticoid receptor antagonist. In total, 54.4% of patients were receiving devicebased therapies.
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4 Journal of Cardiovascular Nursing x Month 2016 TABLE 2
Baseline Characteristics
Age, years Female BMI, kg/m2 Underweight (BMI G18.5 kg/m2) Ideal weight (BMI 18.5Y24.9 kg/m2) Overweight (BMI 25.0Y29.9 kg/m2) Obese (BMI Q30.0 kg/m2) NYHA functional class II III Etiology of heart failure IHD Non-IHD Loop diuretic ACE inhibitor ARB ACE inhibitor or ARB "-blocker Aldosterone antagonist Digoxin ICD CRTD
64.5 T 9.3 15 (19.0) 29.7 T 5.6 2 (2.6) 10 (12.8) 28 (35.9) 38 (48.7) 63 (79.7) 16 (20.3) 51 28 57 55 23 77 74 41 16 43 23
(64.6) (35.4) (72.2) (69.6) (29.1) (97.5) (93.7) (51.9) (20.3) (54.4) (29.1)
Values are mean T SD or n (%); n = 79 with the exception of BMI, which was not measured in 1 patient. Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BMI, body mass index; CRTD, cardiac resynchronization therapy with implantable cardioverter defibrillator; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; NYHA, New York Heart Association.
Mean daily energy and macronutrient intakes reported by the patients are presented in Table 3. Reported intakes of fruit and vegetables were high, with 63 patients (79.7%) meeting the current UK recommendation30 of at least 5 portions per day. Intakes of oily fish were low, with 25 patients (31.6%) meeting the current UK recommendation31 of at least 1 portion per week. Mean alcohol intake was 0.8 units (6.4 g) per day. The European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 suggest that patients with heart failure should consume no more than 2 units (16 g) of alcohol in men or 1 unit (8 g) in women per day.1 Table 4 shows mean daily micronutrient intake reported by the patients alongside a comparison with Endocrine Society recommended dietary intakes for vitamin D27 and UK dietary reference values for all other micronutrients.28 More than 80% of patients reported intakes above the RNI for all micronutrients with the exception of riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the LRNI or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Reported intakes of vitamin D, selenium, and iodine were notably low. No patients reported an intake greater than the minimum recommended intake for vitamin D, and
36.7% and 26.6% of patients reported intakes less than the LRNI for selenium and iodine, respectively. Micronutrient status data were available for 78 patients (not measured in 1 patient). Table 5 shows mean blood concentration of ferritin, vitamin D, vitamin B6, vitamin B12, and folate in the patients, along with cutoffs for deficiency.27,32Y35 Vitamin D deficiency was common; 75.6% of patients had a plasma total 25-hydroxyvitamin D concentration of less than 50 nmol/L and 20 patients (25.6%) had a 25-hydroxy-vitamin D concentration of less than 25 nmol/L. A vitamin B6 concentration less than the normal range was observed in 17.9% of patients. A folate concentration less than the normal range was observed in 11.5% of patients. Less than 10% of patients had a vitamin B12 concentration less than the normal range. No patient had a ferritin concentration less than the normal range. Table 5 also includes information on dietary micronutrient intake for those patients with evidence of micronutrient deficiency. With the exception of vitamin D (all patients within the study population reported a dietary intake of vitamin D less than that recommended), no patient with micronutrient deficiency reported a level of dietary intake that was less than the recommended amount. There was no significant difference in the mean intake of 5 different food groups that contribute to vitamin D intake (fish and fish dishes, meat and meat products, cereals and cereal products, eggs and egg dishes, and fat spreads) between individuals from 3 vitamin D status groups: plasma total 25-hydroxy-vitamin D concentration less than 25 nmol/L, 25 to 50 nmol/L, and greater than 50 nmol/L (data not shown).
Discussion In this observational study of patients with chronic stable heart failure, based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.
TABLE 3 Mean Energy and Macronutrient Intake for a Sample of Patients With Heart Failure (n = 79), Assessed Using a Food Frequency Questionnaire Total energy, kcal/d Total energy, kcal/kg Food energy, kcal/d Protein, g/kg Protein, % food energy Fat, % food energy Carbohydrate, % food energy
2207.5 26.4 2161.1 0.9 15.3 33.0 55.1
Values are mean T SD.
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T T T T T T T
1094.0 13.5 1092.6 0.4 3.4 6.0 8.1
Micronutrient Intake and Status in Heart Failure Patients 5 TABLE 4
Mean Micronutrient Intake and Comparison With Recommended Intake for a Sample of Patients With Heart Failure (n = 79), Assessed Using a Food Frequency Questionnaire Number (%) Reporting an Intake Greater Than or Equal to RNI or Recommended Intake
Mean Intake Vitamin D, 2g/d Selenium, 2g/d Iodine, 2g/d Copper, mg/d Calcium, mg/d Magnesium, mg/d Riboflavin, mg/d Potassium, mg/d Zinc, mg/d Vitamin A, 2g/d Iron, mg/d Chloride, mg/d Niacin, mg/d Sodium, mg/d Vitamin B12, 2g/d Folate, 2g/d Vitamin C, mg/d Vitamin B6, mg/d Phosphorus, mg/d Thiamin, mg/d Vitamin E, mg/d
2.8 47.5 100.1 1.2 696.9 302.2 1.5 4041.5 8.7 1015.1 13.5 4217.5 23.4 2830.2 4.0 397.8 199.6 2.9 1253.6 2.0 9.2
T T T T T T T T T T T T T T T T T T T T T
2.0 19.4 63.4 0.6 158.7 122.1 0.8 1547.0 3.7 593.9 5.6 1879.1 9.9 1229.2 1.9 184.7 109.3 1.1 569.2 0.8 5.7
Number (%) Reporting an Intake Less Than LRNI a
0 (0%) 8 (10.1) 12 (15.2) 27 (34.2) 32 (40.5) 36 (45.6) 46 (58.2) 47 (59.5) 54 (68.4) 58 (73.4) 68 (86.1) 70 (88.6) 70 (88.6) 70 (88.6) 75 (94.9) 75 (94.9) 76 (96.2) 77 (97.5) 77 (97.5) 78 (98.7)
29 (36.7) 16 (20.3) b
13 (16.5) 8 (10.1) 6 (7.6) 4 (5.1) 7 (8.9) 5 (6.3) 1 (1.3) 0 (0.0) 2 (2.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
c
c
Values are mean T SD or n (%). Abbreviations: LRNI, lower reference nutrient intake; RNI, reference nutrient intake. a The Endocrine Society Clinical Practice Guideline27 does not report a LRNI for vitamin D. b LRNI not reported. c Recommended intake not reported.
Previously published studies have demonstrated reduced intake of thiamine,13,15,16 riboflavin,14,16,18 niacin,14,16 vitamin B6,14,16,18 folate,14,18 vitamin C,14,16 vitamin D,13,18 vitamin A,14 vitamin E,14,18 calcium,14,17 magnesium,15,17 iron,14,18 zinc,14,15 and selenium11 in patients with heart failure compared with recommended intakes or control patients free from the condition. In general, these studies have involved small numbers of patients with varying definitions of heart failure and different methods of assessing dietary intake. This makes comparisons between studies difficult. However, the mean intakes of most micronutrients in the present study were similar to those reported in other published studies, with the exception of folate, vitamin C, and potassium, which were markedly higher in the present
study. This may reflect the high fruit and vegetable intake reported in the present study or suboptimal accuracy of FFQ completion (see below). It is also important to note that estimation of dietary intake of vitamin A and selenium is difficult using an FFQ.36,37 The reason patients with heart failure may have reduced dietary intake of micronutrients is not clear. However, a study by Lennie et al38 involving 67 patients with heart failure suggests that factors such as decreased hunger sensation, diet restrictions, fatigue, shortness of breath, nausea, anxiety, and sadness may contribute to decreased nutritional intake. The major finding from the present study in relation to micronutrient status was the large proportion of patients with evidence of vitamin D deficiency. All patients
TABLE 5
Blood Concentrations of Micronutrients and Comparison With Dietary Intake in a Sample of Patients With Heart Failure (n = 78)
Mean (SD) Ferritin, 2g/L Vitamin D, nmol/L Vitamin B6 nmol/L Vitamin B12, ng/L Folate, 2g/L
168.6 39.4 57.2 384.4 7.2
(154.0) (19.6) (30.8) (200.0) (3.8)
Deficiency (Reference) G15.0 G50.0 G30.0 G200.0 G3.0
(31) (27) (32) (33) (34)
Number (%) Deficient 0 59 14 5 9
(0.0) (75.6) (17.9) (6.4) (11.5)
Number Deficient and Also Reporting a Dietary Intake GRNI or Recommended Intake
Number Deficient and Also Reporting a Dietary Intake GLRNI
0 59 0 0 0
Abbreviations: LRNI, lower reference nutrient intake; RNI, reference nutrient intake. a Endocrine Society Clinical Practice Guideline27 does not report a LRNI for vitamin D.
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0 a
0 0 0
6 Journal of Cardiovascular Nursing x Month 2016 in the present study also reported a dietary intake of vitamin D below recommended levels, and this may be a factor contributing to low status in this population. However, low dietary intake is likely to be only a part of this story; in this study, there were no significant differences in the dietary intake of the 5 main food groups that contribute to vitamin D intake in patients who had sufficient versus deficient vitamin D status. A number of case-control studies have demonstrated reduced vitamin D status in patients with heart failure compared with controls free from the condition.19 In the present study, few patients (3.8%) had evidence of vitamin B12 deficiency, 11.6% had evidence of folate deficiency, and 17.9% had evidence of vitamin B6 deficiency. Few studies have investigated vitamin B6 or vitamin B12 status in patients with heart failure. A casecontrol study involving 100 patients with heart failure and 50 age- and sex-matched controls suggested that vitamin B6 deficiency was more common in patients with heart failure.39 Observational studies investigating vitamin B12 status in patients with heart failure or impaired left ventricular systolic function have yielded inconsistent results.40,41 In the present study, no patient had a blood ferritin concentration less than the normal range. This finding is in contrast to previous studies suggesting a high prevalence of iron deficiency in patients with heart failure.42 With the exception of vitamin D, there was no evidence of an association between micronutrient deficiency and reduced dietary intake. However, the total number of patients with a blood concentration of ferritin, vitamin B6, vitamin B12, or folate less than the normal range was low (28 patients in total), making such comparisons difficult. Study Strengths The present study has a number of strengths. First, the study population is one of the largest when compared with other observational studies that assessed dietary intake in patients with heart failure. In addition, when compared with a recent large clinical trial involving patients with heart failure,43 the present study population is representative of a typical population with heart failure with a reduced ejection fraction. In particular, most patients were receiving contemporary, evidence-based therapies for heart failure, including a substantial proportion that was receiving device-based therapies. Finally, dietary intake of a wide range of micronutrients was measured alongside blood concentrations of ferritin and a selected number of micronutrients in the same population. Study Limitations This study also has a number of limitations, the most important being the lack of a control group free from heart failure. All conclusions regarding reduced micro-
nutrient intake or micronutrient status are derived from comparisons with recommendations for dietary intake of micronutrients and reference values for micronutrient status. It is therefore impossible to determine if any of the observed findings have any specific relationship to the diagnosis of heart failure. This is of particular importance with respect to the large proportion of patients with evidence of vitamin D deficiency, given that large observational studies have reported a high prevalence of suboptimal vitamin D status in healthy populations.44 The study population was largely male, and the observed results may not be generalizable to females with heart failure. In addition, patients receiving a multivitamin or mineral supplement or vitamin DYcontaining fish oil were excluded from participating in this study, and this may have influenced the results observed. It is possible that other patients with heart failure may use such supplements to compensate for low dietary intake of micronutrients. The accuracy of intakes reported in the FFQ may also be suboptimal. In the present study, most patients reported an average intake of more than 5 portions of fruit and vegetables per day. This may not truly reflect fruit and vegetable intake in this population because the most recent data from the National Diet and Nutrition Survey rolling program 2008Y2012 indicates that 30% and 41% of adults and older adults, respectively, were meeting the 5-a-day recommendation.45 Indeed, FFQs are prone to measurement error. Overreporting of foods perceived to be ‘‘healthy,’’ particularly foods such as fruit and vegetables, has been reported with the European Prospective Investigation into Cancer and Nutrition and other FFQs.46,47 Most patients (84.6%) in this study were overweight. As a result, underweight and ideal-weight patients are underrepresented. This may also have relevance with respect to the accuracy of intakes reported in the FFQ because underreporting of dietary intake tends to be common in obese individuals.48 However, the mean reported energy intake in this study (26.4 kcal/kg) would suggest that underreporting of nutritional intake was not an issue. Finally, the European Prospective Investigation into Cancer and Nutrition FFQ used in the present study was developed for use in large-scale epidemiological studies21 and may therefore be less suitable for smaller sample sizes.
Conclusions Vitamin D deficiency was very common in this group of patients with chronic stable heart failure. In addition, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.
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Micronutrient Intake and Status in Heart Failure Patients 7
What’s New and Important h Patients with heart failure may not consume enough micronutrients to meet their needs. h Patients with heart failure with a reduced ejection fraction may be deficient in vitamin D.
Acknowledgments The authors thank Dr Sarah Gilchrist, Mr Cyril McMaster, and Dr Caroline Mercer for their help with laboratory analysis. REFERENCES 1. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Eur Heart J. 2012;33(14): 1787Y1847. 2. Anker SD, Ponikowski P, Varney S, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997;349(9058):1050Y1053. 3. Woodside JV, McCall D, McGartland C, Young IS. Micronutrients: dietary intake v. supplement use. Proc Nutr Soc. 2005;64(4):543Y553. 4. McKeag NA, McKinley MC, Woodside JV, Harbinson MT, McKeown PP. The role of micronutrients in heart failure. J Acad Nutr Diet. 2012;112(6):870Y886. 5. Gotsman I, Shauer A, Zwas DR, et al. Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. Eur J Heart Fail. 2012;14(4):357Y366. 6. Liu LC, Voors AA, van Veldhuisen DJ, et al. Vitamin D status and outcomes in heart failure patients. Eur J Heart Fail. 2011;13(6):619Y625. 7. Pilz S, Ma¨rz W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93(10): 3927Y3935. 8. Zittermann A, Schleithoff SS, Go¨tting C, et al. Poor outcome in end-stage heart failure patients with low circulating calcitriol levels. Eur J Heart Fail. 2008;10(3):321Y327. 9. Cohen-Solal A, Leclercq C, Deray G, et al. Iron deficiency: an emerging therapeutic target in heart failure. Heart. 2014; 100(18):1414Y1420. 10. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436Y2448. 11. de Lorgeril M, Salen P, Accominotti M, et al. Dietary and blood antioxidants in patients with chronic heart failure: insights into the potential importance of selenium in heart failure. Eur J Heart Fail. 2001;3(6):661Y669. 12. Gorelik O, Almoznino-Sarafian D, Feder I, et al. Dietary intake of various nutrients in older patients with congestive heart failure. Cardiology. 2003;99(4):177Y181. 13. Price RJ, Witham MD, McMurdo ME. Defining the nutritional status and dietary intake of older heart failure patients. Eur J Cardiovasc Nurs. 2007;6(3):178Y183. 14. Catapano G, Pedone C, Nunziata E, Zizzo A, Passantino A, Incalzi RA. Nutrient intake and serum cytokine pattern in elderly people with heart failure. Eur J Heart Fail. 2008; 10(4):428Y434.
15. Louren0o BH, Vieira LP, Macedo A, Nakasato M, Marucci Mde F, Bocchi EA. Nutritional status and adequacy of energy and nutrient intakes among heart failure patients. Arq Bras Cardiol. 2009;93(5):541Y548. 16. Arcand J, Floras V, Ahmed M, et al. Nutritional inadequacies in patients with stable heart failure. J Am Diet Assoc. 2009; 109(11):1909Y1913. 17. Lemon SC, Olendzki B, Magner R, et al. The dietary quality of persons with heart failure in NHANES 1999Y2006. J Gen Intern Med. 2010;25(2):135Y140. 18. Hughes CM, Woodside JV, McGartland C, Roberts MJ, Nicholls DP, McKeown PP. Nutritional intake and oxidative stress in chronic heart failure. Nutr Metab Cardiovasc Dis. 2012;22(4):376Y382. 19. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Ko¨rfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol. 2003;41(1):105Y112. 20. McKeag NA, McKinley MC, Harbinson MT, et al. The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial. JACC Heart Fail. 2014;2(3):308Y317. 21. Ocke´ MC, Bueno-de-Mesquita HB, Goddijn HE, et al. The Dutch EPIC food frequency questionnaire. I. Description of the questionnaire, and relative validity and reproducibility for food groups. Int J Epidemiol. 1997;26(suppl 1):S37YS48. 22. Ocke´ MC, Bueno-de-Mesquita HB, Pols MA, Smit HA, van Staveren WA, Kromhout D. The Dutch EPIC food frequency questionnaire. II. Relative validity and reproducibility for nutrients. Int J Epidemiol. 1997;26(suppl 1):S49YS58. 23. Day N, McKeown N, Wong M, Welch A, Bingham S. Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium. Int J Epidemiol. 2001; 30(2):309Y317. 24. van Liere MJ, Lucas F, Clavel F, Slimani N, Villeminot S. Relative validity and reproducibility of a French dietary history questionnaire. Int J Epidemiol. 1997;26(suppl 1):S128YS136. 25. Bingham SA, Gill C, Welch A, et al. Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers. Int J Epidemiol. 1997;26(suppl 1):S137YS151. 26. Crawley H. Food Portion Sizes. London, England: HMSO; 1988. 27. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911Y1930. 28. Department of Health. Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. London, England: HMSO; 1991. 29. Henderson L, Irving K, Gregory J, et al. The National Diet and Nutrition Survey: Adults Aged 19 to 64 Years. Volume 3: Vitamin and Mineral Intake and Urinary Analytes. London, England: HMSO; 2003. 30. National Health Service. NHS choices Why 5 A DAY? http:// www.nhs.uk/Livewell/5ADAY/Pages/Why5ADAY. Accessed October 2014. 31. National Health Service. NHS choices Fish and shellfish. http://www.nhs.uk/livewell/goodfood/pages/fishshellfish.aspx. Accessed October 2014. 32. World Health Organisation. Serum Ferritin Concentrations for the Assessment of Iron Status and Iron Deficiency in Populations. Geneva, Switzerland: World Health Organisation; 2011.
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8 Journal of Cardiovascular Nursing x Month 2016 33. Leklem JE. Vitamin B-6: a status report. J Nutr. 1990; 120(suppl 11):1503Y1507. 34. Carmel R. Cobalamin (vitamin B12). In: Ross A, Caballero B, Cousins R, Tucker K, Zieger T, eds. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins; 2014;369Y389. 35. World Health Organisation. Serum and Red Blood Cell Folate Concentrations for Assessing Folate Status in Populations. Geneva, Switzerland: World Health Organisation; 2012. 36. Roidt L, White E, Goodman GE, et al. Association of food frequency questionnaire estimates of vitamin A intake with serum vitamin A levels. Am J Epidemiol. 1988;128(3):645Y654. 37. Karita K, Sasaki S, Ishihara J, Tsugane S, JHPC. Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study to assess selenium intake: comparison with dietary records and blood levels. J Epidemiol. 2003;13(1 suppl):S92YS97. 38. Lennie TA, Moser DK, Heo S, Chung ML, Zambroski CH. Factors influencing food intake in patients with heart failure: a comparison with healthy elders. J Cardiovasc Nurs. 2006; 21(2):123Y129. 39. Keith ME, Walsh NA, Darling PB, et al. B-vitamin deficiency in hospitalized patients with heart failure. J Am Diet Assoc. 2009;109(8):1406Y1410. 40. Herzlich BC, Lichstein E, Schulhoff N, et al. Relationship among homocyst(e)ine, vitamin B-12 and cardiac disease in the elderly: association between vitamin B-12 deficiency and
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Vol. 00, No. 0, pp 00Y00 x Copyright B 2016 Wolters Kluwer Health, Inc. All rights reserved.
Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure An Observational Study Nicholas A. McKeag, MB, BCh, PhD; Michelle C. McKinley, PhD; Mark T. Harbinson, MD; Ann McGinty, PhD; Charlotte E. Neville, PhD; Jayne V. Woodside, PhD; Pascal P. McKeown, MD Background: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status. Objective: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure. Methods: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion. Results: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration G50 nmol/L) was observed in 75.6% of patients. Conclusions: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs. KEY WORDS:
heart failure, macronutrients, micronutrients, nutrition
H
eart failure is a syndrome comprising symptoms such as breathlessness, alongside signs of fluid retention such as pulmonary congestion or ankle swelling, resulting from an abnormality of cardiac structure
Nicholas A. McKeag, MB, BCh, PhD Clinical Research Fellow, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom.
Michelle C. McKinley, PhD Senior Lecturer, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Mark T. Harbinson, MD Senior Lecturer, Centre for Medical Education, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom.
Ann McGinty, PhD Lecturer, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Charlotte E. Neville, PhD Research Fellow, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
or function.1 Poor nutritional status is associated with mortality in patients with heart failure.2 Micronutrients (defined as substances needed only in small amounts for normal body function3) may play an important role
Jayne V. Woodside, PhD Professor, Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, Belfast, United Kingdom.
Pascal P. McKeown, MD Professor, Centre for Medical Education, School of Medicine, Dentistry & Biomedical Sciences, Queen’s University, and The Heart Centre, Belfast Health & Social Care Trust, United Kingdom. This work was supported by a Northern Ireland Health & Social Care R&D Doctoral Fellowship Award and a Northern Ireland Chest Heart & Stroke Association Grant. Nicholas A. McKeag: honorarium from Biotronik, Laboratoires Servier, Medtronic, Menarini Pharma UK, Sorin Group, and St Jude Medical. The other authors have no conflicts of interest to disclose.
Correspondence Nicholas A. McKeag, MB, BCh, PhD, Centre for Public Health, Queen’s University Belfast, Institute of Clinical Sciences Block B, Grosvenor Road, Belfast BT12 6BJ, United Kingdom ([email protected]). DOI: 10.1097/JCN.0000000000000322
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2 Journal of Cardiovascular Nursing x Month 2016 in heart failure. Observational studies suggest that patients with heart failure may have a tendency to reduced or suboptimal status of a number of micronutrients, including vitamin A, vitamin C, thiamine, vitamin B12, vitamin D, selenium, copper, and zinc.4 Micronutrient deficiency in patients with heart failure may be associated with an adverse prognosis. A number of large observational studies have suggested that vitamin D deficiency or suboptimal status is associated with mortality in patients with heart failure.5Y8 Iron deficiency is also common in patients with heart failure, with a prevalence of up to 50%, and is associated with an increased risk of death.9 In a large intervention study involving patients with heart failure and evidence of iron deficiency, treatment with intravenous iron was associated with an improvement in symptoms, functional capacity, and quality of life.10 The mechanism for suboptimal micronutrient status in patients with heart failure is not clear. A small number of observational studies, using varying methods of dietary assessment, have suggested that patients with heart failure have reduced dietary intake of a wide range of micronutrients.11Y18 Very few of these studies investigated dietary micronutrient status alongside micronutrient intake. The aims of this study were to assess dietary micronutrient intake and micronutrient status in patients with chronic stable heart failure and to examine differences in dietary intake across 3 vitamin D status subgroups. A wide-ranging group of micronutrients was chosen for dietary intake assessment because previous studies have suggested reduced intake of a large number of different micronutrients. With respect to micronutrient status, the micronutrients assessed were chosen because of previous data suggesting suboptimal status in patients with heart failure (particularly vitamin D and ferritin9,19). Study Overview and Participants This was an observational study performed at a single tertiary referral hospital in Belfast, Northern Ireland. The study was approved by the Office for Research Ethics Committee Northern Ireland. All patients provided written informed consent before participation. The study is based on data collected at baseline from patients who participated in the Micronutrient Supplementation in Patients With Heart Failure study, a clinical trial conducted to investigate the effect of multiple micronutrient supplementation in patients with chronic stable heart failure.20 Patients were invited to take part in the study at hospital-based heart failure outpatient clinics in Northern Ireland. Inclusion and exclusion criteria are listed in Table 1. Patients receiving a multivitamin or mineral supplement or vitamin DYcontaining fish oil were excluded from participating in this study.
Baseline Characteristics and Dietary Intake Assessment The baseline characteristics of patients taking part in the study were collected by a trained member of the research team (doctor or registered nurse) using a standardized questionnaire. Patients were asked to complete a modified version of the European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ), similar to that used in the US Nurses’ Health Study.21,22 This semiquantitative FFQ, including 130 food items, was used to assess food and nutrient intake during the previous year. The FFQ was adapted to include foods that are commonly consumed within the United Kingdom and Northern Ireland and has been validated within the UK population.23 For each food item, participants indicated their usual consumption over the previous year from 9 frequency categories (never/less than once a month, 1Y3 per month, once a week, 2Y4 per week, 5Y6 per week, once a day, 2Y3 per day, 4Y5 per day, or more than 6 per day). The FFQ is semiquantitative and so does not include specific questions on portion size, but rather, it asks participants to estimate their intake in terms of how many medium portions were consumed; what is meant by ‘‘medium’’ is described in the FFQ according to natural (eg, slice of bread) or household (eg, glass, cup, or spoon) units. An explanation of how to complete the questionnaire was provided by a trained member of the research team. Patients were asked to indicate how often on average they had eaten the specified amount of each food item during the past year. A completed example page was provided for review. The FFQ was completed by the patient in a private research office with a trained member of the research team present to answer any questions. It took patients approximately 20 to 30 minutes to complete the FFQ. This FFQ has been compared with 24-hour recalls and 24-hour urinary nitrogen excretion in subjects from the Netherlands21,22 and France24 and 4-day weighted records and 24-hour urinary nitrogen excretion in subjects from the United Kingdom.25 Overall, these studies indicate good reproducibility and modest to good validity. Nutrient intake was calculated using the method described by Bingham et al.25 Briefly, the selected frequency of consumption for each food item was multiplied by a standard portion weight to obtain a daily intake in grams per day. The weights of natural or household units were derived from those used in previous dietary surveys and from published values.25,26 Mean energy and nutrient intakes for foods were then calculated using a computerized food analysis database (Weighed Intake Software Program; Tinuviel Software, Warrington, United Kingdom) based on UK food composition tables.
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Micronutrient Intake and Status in Heart Failure Patients 3 TABLE 1 Inclusion and Exclusion Criteria in the Micronutrient Supplementation in Patients With Heart Failure Study20 Inclusion criteria Age 18Y80 y New York Heart Association symptomatic class II or III On best known medical treatment (on or tried on and unable to tolerate an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a "-blocker) Stable for 6 wks (no acute exacerbations of heart failure and no changes to heart failure treatment) Left ventricular ejection fraction e45% (measured by echocardiography, contrast ventriculography, cardiovascular magnetic resonance imaging or radionuclide ventriculography) Exclusion criteria Alcohol intake > 40 units (320 g) per week Severe renal impairment (glomerular filtration rate G 30 mL/min) Severe hepatic dysfunction (known significant liver disease or serum transaminases greater than 3 times the upper limit of normal) Atrial fibrillation in the absence of a pacemaker Frequent ventricular ectopics On waiting list for cardiac transplantation Uncontrolled diabetes mellitus Inability to give informed consent Estimated life span G12 mo Already taking a multivitamin or mineral supplement or vitamin DYcontaining fish oil Woman of child-bearing potential Personal history of renal stones, hypercalcemia, sarcoidosis, hemochromatosis, or lactose intolerance
Micronutrient intake was compared with the Endocrine Society Clinical Practice Guideline for vitamin D27 and UK dietary reference values for all other micronutrients.28 The UK dietary reference values are reported in the form of a reference nutrient intake (RNI) and a lower reference intake (LRNI). The RNI for a nutrient represents the amount of that nutrient that is sufficient or more than sufficient for approximately 97.5% of a group. Intakes above this limit are almost certainly adequate for most individuals. The LRNI for a nutrient represents the amount of that nutrient that is sufficient or more than sufficient for only a small proportion of a group (2.5% of people). Intakes below this limit are almost certainly inadequate for most individuals.25 Measurement of Micronutrient Status Serum ferritin concentration was measured using an electrochemiluminescence immunoassay (Roche Diagnostics, Burgess Hill, United Kingdom). Serum concentrations of vitamin B12 and folate were measured using chemiluminescent microparticle assays (Roche Diagnostics). Serum vitamin D concentration was measured using ultra performance liquid chromatography followed by tandem mass spectrometry13 (Waters Corporation, Milford, Massachusetts). This method measures both 25-hydroxy-vitamin D2 and 25-hydroxy-vitamin D3, and results are presented as total 25-hydroxy-vitamin D. Plasma vitamin B6 concentration (pyridoxal phosphate) was measured using high-performance liquid chromatography with fluorescence detection (Chromsystems Instruments & Chemicals GmbH, Gra¨felfing, Germany). All assays were closely monitored for performance, and all interassay and intra-assay coefficients of variation
were less than 15%. Fasting blood samples were drawn at the time of FFQ completion. Statistics Results are presented as mean T SD for continuous variables and number (percentage) for categorical variables. Mean intake in grams of 5 food groups (fish and fish dishes, meat and meat products, cereals and cereal products, eggs and egg dishes, and fat spreads) that are recognized as the main sources of vitamin D in the diet29 was examined across 3 vitamin D status groups (plasma total 25-hydroxy-vitamin D concentration G25 nmol/L, 25Y50 nmol/L, and >50 nmol/L) using analysis of variance. All analyses were performed with IBM SPSS Statistics version 20 (IBM Corporation, New York, New York).
Results Seventy-nine patients were recruited. Baseline characteristics are presented in Table 2. The mean age of participants was 64.5 years and 19.0% were women. Patients were, on average, overweight, with a mean body mass index of 29.7 kg/m2. Ischemic heart disease was twice as common as nonYischemic heart disease with respect to etiology of heart failure. Most (79.7%) patients were New York Heart Association functional class II. Most patients were receiving current best drug therapy for heart failure, with nearly all receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (97.5%) and "-blocker (93.7%) and 51.9% receiving a mineralocorticoid receptor antagonist. In total, 54.4% of patients were receiving devicebased therapies.
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4 Journal of Cardiovascular Nursing x Month 2016 TABLE 2
Baseline Characteristics
Age, years Female BMI, kg/m2 Underweight (BMI G18.5 kg/m2) Ideal weight (BMI 18.5Y24.9 kg/m2) Overweight (BMI 25.0Y29.9 kg/m2) Obese (BMI Q30.0 kg/m2) NYHA functional class II III Etiology of heart failure IHD Non-IHD Loop diuretic ACE inhibitor ARB ACE inhibitor or ARB "-blocker Aldosterone antagonist Digoxin ICD CRTD
64.5 T 9.3 15 (19.0) 29.7 T 5.6 2 (2.6) 10 (12.8) 28 (35.9) 38 (48.7) 63 (79.7) 16 (20.3) 51 28 57 55 23 77 74 41 16 43 23
(64.6) (35.4) (72.2) (69.6) (29.1) (97.5) (93.7) (51.9) (20.3) (54.4) (29.1)
Values are mean T SD or n (%); n = 79 with the exception of BMI, which was not measured in 1 patient. Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BMI, body mass index; CRTD, cardiac resynchronization therapy with implantable cardioverter defibrillator; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; NYHA, New York Heart Association.
Mean daily energy and macronutrient intakes reported by the patients are presented in Table 3. Reported intakes of fruit and vegetables were high, with 63 patients (79.7%) meeting the current UK recommendation30 of at least 5 portions per day. Intakes of oily fish were low, with 25 patients (31.6%) meeting the current UK recommendation31 of at least 1 portion per week. Mean alcohol intake was 0.8 units (6.4 g) per day. The European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 suggest that patients with heart failure should consume no more than 2 units (16 g) of alcohol in men or 1 unit (8 g) in women per day.1 Table 4 shows mean daily micronutrient intake reported by the patients alongside a comparison with Endocrine Society recommended dietary intakes for vitamin D27 and UK dietary reference values for all other micronutrients.28 More than 80% of patients reported intakes above the RNI for all micronutrients with the exception of riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the LRNI or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Reported intakes of vitamin D, selenium, and iodine were notably low. No patients reported an intake greater than the minimum recommended intake for vitamin D, and
36.7% and 26.6% of patients reported intakes less than the LRNI for selenium and iodine, respectively. Micronutrient status data were available for 78 patients (not measured in 1 patient). Table 5 shows mean blood concentration of ferritin, vitamin D, vitamin B6, vitamin B12, and folate in the patients, along with cutoffs for deficiency.27,32Y35 Vitamin D deficiency was common; 75.6% of patients had a plasma total 25-hydroxyvitamin D concentration of less than 50 nmol/L and 20 patients (25.6%) had a 25-hydroxy-vitamin D concentration of less than 25 nmol/L. A vitamin B6 concentration less than the normal range was observed in 17.9% of patients. A folate concentration less than the normal range was observed in 11.5% of patients. Less than 10% of patients had a vitamin B12 concentration less than the normal range. No patient had a ferritin concentration less than the normal range. Table 5 also includes information on dietary micronutrient intake for those patients with evidence of micronutrient deficiency. With the exception of vitamin D (all patients within the study population reported a dietary intake of vitamin D less than that recommended), no patient with micronutrient deficiency reported a level of dietary intake that was less than the recommended amount. There was no significant difference in the mean intake of 5 different food groups that contribute to vitamin D intake (fish and fish dishes, meat and meat products, cereals and cereal products, eggs and egg dishes, and fat spreads) between individuals from 3 vitamin D status groups: plasma total 25-hydroxy-vitamin D concentration less than 25 nmol/L, 25 to 50 nmol/L, and greater than 50 nmol/L (data not shown).
Discussion In this observational study of patients with chronic stable heart failure, based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.
TABLE 3 Mean Energy and Macronutrient Intake for a Sample of Patients With Heart Failure (n = 79), Assessed Using a Food Frequency Questionnaire Total energy, kcal/d Total energy, kcal/kg Food energy, kcal/d Protein, g/kg Protein, % food energy Fat, % food energy Carbohydrate, % food energy
2207.5 26.4 2161.1 0.9 15.3 33.0 55.1
Values are mean T SD.
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T T T T T T T
1094.0 13.5 1092.6 0.4 3.4 6.0 8.1
Micronutrient Intake and Status in Heart Failure Patients 5 TABLE 4
Mean Micronutrient Intake and Comparison With Recommended Intake for a Sample of Patients With Heart Failure (n = 79), Assessed Using a Food Frequency Questionnaire Number (%) Reporting an Intake Greater Than or Equal to RNI or Recommended Intake
Mean Intake Vitamin D, 2g/d Selenium, 2g/d Iodine, 2g/d Copper, mg/d Calcium, mg/d Magnesium, mg/d Riboflavin, mg/d Potassium, mg/d Zinc, mg/d Vitamin A, 2g/d Iron, mg/d Chloride, mg/d Niacin, mg/d Sodium, mg/d Vitamin B12, 2g/d Folate, 2g/d Vitamin C, mg/d Vitamin B6, mg/d Phosphorus, mg/d Thiamin, mg/d Vitamin E, mg/d
2.8 47.5 100.1 1.2 696.9 302.2 1.5 4041.5 8.7 1015.1 13.5 4217.5 23.4 2830.2 4.0 397.8 199.6 2.9 1253.6 2.0 9.2
T T T T T T T T T T T T T T T T T T T T T
2.0 19.4 63.4 0.6 158.7 122.1 0.8 1547.0 3.7 593.9 5.6 1879.1 9.9 1229.2 1.9 184.7 109.3 1.1 569.2 0.8 5.7
Number (%) Reporting an Intake Less Than LRNI a
0 (0%) 8 (10.1) 12 (15.2) 27 (34.2) 32 (40.5) 36 (45.6) 46 (58.2) 47 (59.5) 54 (68.4) 58 (73.4) 68 (86.1) 70 (88.6) 70 (88.6) 70 (88.6) 75 (94.9) 75 (94.9) 76 (96.2) 77 (97.5) 77 (97.5) 78 (98.7)
29 (36.7) 16 (20.3) b
13 (16.5) 8 (10.1) 6 (7.6) 4 (5.1) 7 (8.9) 5 (6.3) 1 (1.3) 0 (0.0) 2 (2.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
c
c
Values are mean T SD or n (%). Abbreviations: LRNI, lower reference nutrient intake; RNI, reference nutrient intake. a The Endocrine Society Clinical Practice Guideline27 does not report a LRNI for vitamin D. b LRNI not reported. c Recommended intake not reported.
Previously published studies have demonstrated reduced intake of thiamine,13,15,16 riboflavin,14,16,18 niacin,14,16 vitamin B6,14,16,18 folate,14,18 vitamin C,14,16 vitamin D,13,18 vitamin A,14 vitamin E,14,18 calcium,14,17 magnesium,15,17 iron,14,18 zinc,14,15 and selenium11 in patients with heart failure compared with recommended intakes or control patients free from the condition. In general, these studies have involved small numbers of patients with varying definitions of heart failure and different methods of assessing dietary intake. This makes comparisons between studies difficult. However, the mean intakes of most micronutrients in the present study were similar to those reported in other published studies, with the exception of folate, vitamin C, and potassium, which were markedly higher in the present
study. This may reflect the high fruit and vegetable intake reported in the present study or suboptimal accuracy of FFQ completion (see below). It is also important to note that estimation of dietary intake of vitamin A and selenium is difficult using an FFQ.36,37 The reason patients with heart failure may have reduced dietary intake of micronutrients is not clear. However, a study by Lennie et al38 involving 67 patients with heart failure suggests that factors such as decreased hunger sensation, diet restrictions, fatigue, shortness of breath, nausea, anxiety, and sadness may contribute to decreased nutritional intake. The major finding from the present study in relation to micronutrient status was the large proportion of patients with evidence of vitamin D deficiency. All patients
TABLE 5
Blood Concentrations of Micronutrients and Comparison With Dietary Intake in a Sample of Patients With Heart Failure (n = 78)
Mean (SD) Ferritin, 2g/L Vitamin D, nmol/L Vitamin B6 nmol/L Vitamin B12, ng/L Folate, 2g/L
168.6 39.4 57.2 384.4 7.2
(154.0) (19.6) (30.8) (200.0) (3.8)
Deficiency (Reference) G15.0 G50.0 G30.0 G200.0 G3.0
(31) (27) (32) (33) (34)
Number (%) Deficient 0 59 14 5 9
(0.0) (75.6) (17.9) (6.4) (11.5)
Number Deficient and Also Reporting a Dietary Intake GRNI or Recommended Intake
Number Deficient and Also Reporting a Dietary Intake GLRNI
0 59 0 0 0
Abbreviations: LRNI, lower reference nutrient intake; RNI, reference nutrient intake. a Endocrine Society Clinical Practice Guideline27 does not report a LRNI for vitamin D.
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0 a
0 0 0
6 Journal of Cardiovascular Nursing x Month 2016 in the present study also reported a dietary intake of vitamin D below recommended levels, and this may be a factor contributing to low status in this population. However, low dietary intake is likely to be only a part of this story; in this study, there were no significant differences in the dietary intake of the 5 main food groups that contribute to vitamin D intake in patients who had sufficient versus deficient vitamin D status. A number of case-control studies have demonstrated reduced vitamin D status in patients with heart failure compared with controls free from the condition.19 In the present study, few patients (3.8%) had evidence of vitamin B12 deficiency, 11.6% had evidence of folate deficiency, and 17.9% had evidence of vitamin B6 deficiency. Few studies have investigated vitamin B6 or vitamin B12 status in patients with heart failure. A casecontrol study involving 100 patients with heart failure and 50 age- and sex-matched controls suggested that vitamin B6 deficiency was more common in patients with heart failure.39 Observational studies investigating vitamin B12 status in patients with heart failure or impaired left ventricular systolic function have yielded inconsistent results.40,41 In the present study, no patient had a blood ferritin concentration less than the normal range. This finding is in contrast to previous studies suggesting a high prevalence of iron deficiency in patients with heart failure.42 With the exception of vitamin D, there was no evidence of an association between micronutrient deficiency and reduced dietary intake. However, the total number of patients with a blood concentration of ferritin, vitamin B6, vitamin B12, or folate less than the normal range was low (28 patients in total), making such comparisons difficult. Study Strengths The present study has a number of strengths. First, the study population is one of the largest when compared with other observational studies that assessed dietary intake in patients with heart failure. In addition, when compared with a recent large clinical trial involving patients with heart failure,43 the present study population is representative of a typical population with heart failure with a reduced ejection fraction. In particular, most patients were receiving contemporary, evidence-based therapies for heart failure, including a substantial proportion that was receiving device-based therapies. Finally, dietary intake of a wide range of micronutrients was measured alongside blood concentrations of ferritin and a selected number of micronutrients in the same population. Study Limitations This study also has a number of limitations, the most important being the lack of a control group free from heart failure. All conclusions regarding reduced micro-
nutrient intake or micronutrient status are derived from comparisons with recommendations for dietary intake of micronutrients and reference values for micronutrient status. It is therefore impossible to determine if any of the observed findings have any specific relationship to the diagnosis of heart failure. This is of particular importance with respect to the large proportion of patients with evidence of vitamin D deficiency, given that large observational studies have reported a high prevalence of suboptimal vitamin D status in healthy populations.44 The study population was largely male, and the observed results may not be generalizable to females with heart failure. In addition, patients receiving a multivitamin or mineral supplement or vitamin DYcontaining fish oil were excluded from participating in this study, and this may have influenced the results observed. It is possible that other patients with heart failure may use such supplements to compensate for low dietary intake of micronutrients. The accuracy of intakes reported in the FFQ may also be suboptimal. In the present study, most patients reported an average intake of more than 5 portions of fruit and vegetables per day. This may not truly reflect fruit and vegetable intake in this population because the most recent data from the National Diet and Nutrition Survey rolling program 2008Y2012 indicates that 30% and 41% of adults and older adults, respectively, were meeting the 5-a-day recommendation.45 Indeed, FFQs are prone to measurement error. Overreporting of foods perceived to be ‘‘healthy,’’ particularly foods such as fruit and vegetables, has been reported with the European Prospective Investigation into Cancer and Nutrition and other FFQs.46,47 Most patients (84.6%) in this study were overweight. As a result, underweight and ideal-weight patients are underrepresented. This may also have relevance with respect to the accuracy of intakes reported in the FFQ because underreporting of dietary intake tends to be common in obese individuals.48 However, the mean reported energy intake in this study (26.4 kcal/kg) would suggest that underreporting of nutritional intake was not an issue. Finally, the European Prospective Investigation into Cancer and Nutrition FFQ used in the present study was developed for use in large-scale epidemiological studies21 and may therefore be less suitable for smaller sample sizes.
Conclusions Vitamin D deficiency was very common in this group of patients with chronic stable heart failure. In addition, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.
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Micronutrient Intake and Status in Heart Failure Patients 7
What’s New and Important h Patients with heart failure may not consume enough micronutrients to meet their needs. h Patients with heart failure with a reduced ejection fraction may be deficient in vitamin D.
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