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Dietary iron intake and serum iron status is not associated with myocardial infarction among adults in the U.S.

M. Beck, N. Harrah, M. Meyer, M. Whitaker, J. Hansen, PhD, RD, LD Graduate Programs in Human Nutrition

Background

Over 1 million people have a myocardial infarction (MI) or heart attack each year; approximately 50% of these individuals die.

In 1981, the “Iron Hypothesis” explained the sex difference in heart disease and iron emerged as a possible risk factor for CVD.

Mechanism: the Oxidative Stress Theory states that free radicals damage tissues, contributing to chronic disease. Excess iron may help catalyze production of free radicals. Therefore, MI events may be partially due to high dietary iron intakes and iron stores in adults, which are hypothesized to increase oxidative stress.

Hypotheses:

1. MI prevalence will be higher among participants with an iron density of ≥ 5 mg/1,000 kcal compared to <5 mg/1,000 kcal

2. MI prevalence will be higher among participants in the highest tertile of serum iron compared to the lowest tertile

3. Iron intake and serum iron will be positively correlated

Methods

Study Design: Cross sectional, retrospective study of 1,847 adults aged 51 years or older who participated in NHANES 2011-2012. Data Collection: Variables that were collected include MI history from the Medical Conditions Questionnaire; iron and caloric intake from two 24-hour dietary recalls; and serum iron from the biochemistry profile. Statistical Analysis: An odds ratio was calculated to assess the association between dietary iron density 5 mg/1000 kcals/day compared to iron density <5 mg/1000 kcals/day and history of MI. A second odds ratio was calculated to assess highest versus lowest tertiles of serum iron and history of MI. A one-sided, unpaired t-test was used to calculate mean serum iron and dietary iron intake between individuals with and without a history of MI. The correlation between serum iron concentration and dietary iron density was assessed with a Pearson’s correlation coefficient.

Figure 1: Exclusion Criteria

NHANES Participants

n = 9,757

Figure 1: Exclusion Criteria NHANES Participants n = 9,757 >51 years of age n = 2,595

>51 years of age

n = 2,595

Participants n = 9,757 >51 years of age n = 2,595 Missing Dietary Data n =

Missing Dietary Data

n = 2,026

years of age n = 2,595 Missing Dietary Data n = 2,026 Missing Serum Iron n

Missing Serum Iron

n = 1,878

Dietary Data n = 2,026 Missing Serum Iron n = 1,878 Missing Biometric Data n =

Missing Biometric Data

n = 1,847

Table 1: Subject Characteristics

Characteristics

Participants (n=1,847)

Age (y)

65 ± 9.2*

BMI (kg/m 2 )

29.3 ± 6.6*

Women (n)

774

Men, (n)

826

Other Hispanic (n)

331

Non-Hispanic White (n)

788

Non-Hispanic Black (n)

510

Other/multiracial (n)

213

* Mean ± Standard Deviation

Figure 2: Association with History of MI

Higher dietary iron 1.38 Higher serum iron 0.78 0.1 Odds Ratio with 95% CI 1
Higher dietary iron
1.38
Higher serum iron
0.78
0.1
Odds Ratio with 95% CI
1
10

Figure 3: Mean Iron Density in Men and Women

12 10 8 mg iron/ 1000 kcal 6 4 7.7 7.9 2 0 Men Women
12
10
8
mg iron/
1000 kcal
6
4
7.7
7.9
2
0
Men
Women

Figure 4: Mean Serum Iron in Men and Women

Serum iron (ug/dL)

125

100

75

50

25

0

90.9

Men

78.7
78.7
78.7
78.7
78.7

78.7

Women

Figure 5: Mean Iron Density and History of MI

mg iron/ 1000 kcal

12 10 8 6 4 8.2 2 0 MI
12
10
8
6
4
8.2
2
0
MI
7.8
7.8
7.8
7.8
7.8

7.8

no MI

Figure 6: Iron Density and Iron Biomarker 360 Y = -0.4076x + 87.817 r =
Figure 6: Iron Density and Iron Biomarker
360
Y = -0.4076x + 87.817
r = -0.039
300
R 2 = 0.0015
240
P = 0.09
Serum
180
Iron
(ug/dL)
120
60
0
0
8
16
24
32
40
Iron Density (iron mg/1000 kcal/day)

Results

134 participants had a history of MI

Odds of MI among participants with an iron density 5 mg/1000 kcal were 38% higher than among participants with an iron density <5 mg/1000 kcal, but this association was not statistically significant (OR: 1.38, 95% CI: 0.71-2.69).

Odds of MI among participants in the highest tertile of serum iron concentration were 22% lower than among participants in the lowest tertile, but this relationship was also not statistically significant (OR:

0.78, 95% CI: 0.51-1.18).

Mean dietary iron intake among those with and without a history of MI was not statistically significant, but trended in the direction of higher intake among those with history of MI (P=0.089, No MI:

x=7.8,SD=3.06, MI: x=8.18 SD=3.08).

There was no significant correlation between iron density and serum iron (r= -0.039, P=0.09).

Strengths

NHANES is a large, representative sample of the United States population

Our study included both dietary and serum iron measures

Dietary iron was expressed as iron density in order to account for caloric variation in participantsdiets

Limitations

Our study did not include iron supplementation

Our study was a retrospective study thus cannot be used to assess causality

Only serum iron was used as a biochemical indicator of dietary iron intake

Conclusion

We found no greater risk for history of MI among individuals with a higher iron density or serum iron concentration, nor did we find a correlation between iron density and serum iron. The latter suggests that serum iron is not a good marker of dietary iron intake. A limitation of our study was that we did not include iron supplementation, which may have limited the range of iron density and serum iron in this population. The average serum iron in the bottom and top tertiles were 53 and 120 mcg/dL, respectively; the normal range is 60-170 mcg/dL. Including supplementation in our study may have yielded greater variation in iron intake.

Future research:

Further research should include iron supplementation data to yield greater variation in iron intake and iron stores. While more research should be done to investigate other markers of iron status used clinically like ferritin or hemoglobin.

Acknowledgements

The team would like to acknowledge Diane Stadler PhD, RD, LD; Jackie Shannon PhD; and Laura Zeigan MA, MLIS MPH, AHIP; Esther Moe PhD, MPH for their contributions to this research project.