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(Circulation. 2001;103:2788.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Low Circulating Vitamin B₆ Is Associated With Elevation of the Inflammation Marker C-Reactive Protein Independently of Plasma Homocysteine Levels

Simonetta Friso, MD; Paul F. Jacques, ScD; Peter W.F. Wilson, MD; Irwin H. Rosenberg, MD; Jacob Selhub, PhD

From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (S.F., P.F.J., I.H.R., J.S.); and Boston University School of Medicine and the National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Mass (P.W.F.W.).

Correspondence to Jacob Selhub, PhD, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail jselhub{at}hnrc.tufts.edu

	Abstract

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Background—Lower vitamin B₆ concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B₆ levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5'-phosphate (PLP), the active form of vitamin B₆, and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship.

Methods and Results—Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. Subjects were divided into 2 groups according to normal or elevated CRP values: group 1, CRP <6 mg/L; group 2, CRP 6 mg/L. Plasma PLP levels were substantially lower in group 2 than in group 1 (mean values in group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1, P<0.001). In a multiple logistic regression model adjusted for tHcy, the association of PLP with CRP remained highly significant (P=0.003).

Conclusions—Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B₆ utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B₆ levels in CVD.

Key Words: atherosclerosis • risk factors • homocysteine • vitamins • inflammation

	Introduction

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Pyridoxal 5'-phosphate (PLP), the active form of vitamin B₆, participates in a wide range of reactions, including metabolism of homocysteine, a sulfur-containing amino acid that is thought to be a risk factor for occlusive vascular disease.^{1 2} Recent studies have shown that plasma PLP levels are significantly reduced in certain pathological conditions. An association with low plasma PLP levels has been demonstrated in patients with rheumatoid arthritis (RA),³ and lower concentrations of this coenzyme have been reported to be an independent risk factor for cardiovascular disease (CVD).^{4 5} Because plasma PLP is an important determinant of plasma total homocysteine (tHcy), an interpretation for a role of this coenzyme has been addressed primarily through its link with homocysteine metabolism. Nevertheless, the relationship between low PLP and diseases cannot be fully explained on the basis of an abnormal tHcy metabolism.^{5 6} Since the first description by Rinehart and Greenberg of arteriosclerotic lesions in pyridoxine-deficient monkeys,⁷ other mechanisms, related or unrelated to the homocysteine pathway, have been proposed for a role of vitamin B₆ in vascular tissue damage. Vitamin B₆ deficiency has been associated with impairment of enzymes involved in determining the structural integrity of the arterial wall,⁸ in altering platelet function,⁹ and in interfering with cholesterol metabolism.¹⁰ Nonetheless, no conclusive mechanism has been identified thus far. An alternative explanation is that the low PLP levels observed in these diseases are linked to inflammatory processes.⁶ As for RA, its chronic inflammatory nature is clearly recognized. There is also growing evidence suggesting that inflammation plays a key part in the pathogenesis of atherosclerosis.¹¹ Indeed, there is an increasing body of evidence supporting the hypothesis that atherosclerosis shares many similarities with RA, a typical chronic inflammatory disease.^{12 13} C-reactive protein (CRP), one of the major acute-phase reactants, as well as cytokines regulating its plasma levels (eg, interleukin-6), have been used to predict the risk of cardiovascular events.¹⁴ Furthermore, it was recently demonstrated that CRP induces adhesion molecule expression in human endothelial cells, supporting the hypothesis of a direct role for CRP in promoting an inflammatory component in the atherosclerotic process.¹⁵ In patients with RA, low plasma PLP levels have been found to be associated also with erythrocyte sedimentation rate and levels of the inflammatory cytokine tumor necrosis factor-.³ More evidence for an inverse correlation between PLP and indices of acute-phase reaction, such as plasma ₁-antichymotrypsin, copper, and blood leukocyte count, was also recently described in a sample of elderly subjects.¹⁶

To evaluate the relationship between plasma PLP, the inflammation marker CRP, and tHcy, we analyzed data available from the 20th examination of the Framingham Heart Study, a well-characterized, population-based cohort.

	Methods

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Study Population
The study sample consisted of the survivors from the original Framingham Heart Study cohort, an epidemiological study established in Framingham, Mass, during the period 1948 through 1950.¹⁷ The original cohort consisted of 5209 subjects of both sexes 30 to 62 years old. The surviving members of this cohort have been examined every 2 years, and in 1988 and 1989, 1402 survivors participated in the 20th examination. Institutional review boards approved the study, and all patients gave informed consent. Characteristics of the study population have been described in detail elsewhere.¹⁸

Additional covariables assessed for the present analyses were age, sex, cigarette smoking, diabetes, history of coronary artery disease, history of CVD, history of stroke events, and history of hypertension. Detailed operational definitions for all these covariables are provided elsewhere.^{19 20}

Laboratory Testing
Samples of venous blood were drawn from each subject to determine the concentration of CRP, tHcy, folate, vitamin B₁₂, and PLP. tHcy was determined by high-performance liquid chromatography with fluorimetric detection.²¹ Plasma folate was measured by a microbial assay (Lactobacillus casei) in a 96-well plate.²² Plasma PLP was assayed by the tyrosine decarboxylase apoenzyme method.²³ Plasma vitamin B₁₂ was measured with a (Magic) radioimmunoassay kit from Ciba-Corning. Serum CRP was determined by an immunoturbidimetric assay (SPQ antibody reagent set II, DiaSorin). Creatinine levels were measured in nonfasting plasma by the Jaffe method, adapted for autoanalyzers. Dietary vitamin B₆ intake was estimated from diet records by use of a semiquantitative food-frequency questionnaire.²⁴

Statistical Analysis
The statistical analyses were confined to a subset of 891 subjects for whom a complete set of CRP, vitamin, and tHcy values was available. To evaluate the relationships among plasma PLP, tHcy, and CRP, we divided the population into 2 groups according to CRP values: group 1, CRP <6 mg/L, ie, within the range of normality (n=834, 93.6%); group 2, CRP 6 mg/L, ie, increased levels (n=57, 6.4%). Distributions of continuous variables were expressed as mean±SD. Logarithmic transformation was performed on all skewed variables to normalize their distributions. Therefore, geometric means (antilogarithms of the transformed means) are presented for tHcy, folate, PLP, vitamin B₁₂, creatinine, albumin, and dietary vitamin B₆ intake. Ninety-five percent CIs for the geometric means were calculated by use of the transformed values, and these intervals are displayed as the antilogarithm of the transformed data. Adjustment for confounding variables (sex, age, smoking, albumin, and creatinine) was performed by general linear model analysis (specifically, ANCOVA) for plasma folate, plasma PLP, vitamin B₁₂, plasma tHcy, albumin, and dietary vitamin B₆ intake. Statistical significance refers to a value of P<0.05. All the statistical computations were performed with an SAS PROC GLM program (SAS user’s guide, version 8.0, SAS Institute, 1999).

	Results

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The relevant characteristics of the study sample divided according to CRP values, ie, group 1, CRP <6 mg/L and group 2, CRP 6 mg/L, are shown in Table 1. As indicated, the 2 groups did not differ with respect to age, sex, plasma folate, vitamin B₁₂, dietary vitamin B₆ intake, and creatinine levels. Neither were they significantly different in terms of clinical characteristics, such as prevalence of hypertension (group 1, 58.6%; group 2, 67.4%, P=0.191), diabetes (group 1, 14.3%; group 2, 13.7%, P>0.2), CVD (group 1, 33.8%; group 2, 36.8%, P>0.2), and coronary heart disease (group 1, 20.4%; group 2, 17.5%, P>0.2). There was a higher prevalence of stroke occurrence in group 2 (12.3%) than in group 1 (6.2%); however, the difference was not statistically significant (P=0.08). Nonsmokers were 88.9% of the population sample, and the cumulative percentage of subjects smoking <10 cigarettes/d was 91.6% (data not shown). Plasma PLP was significantly lower in the group with abnormal CRP values than in the other group (P<0.001). Serum albumin was significantly lower in group 2 than in group 1 (P<0.001). Nevertheless, the difference in albumin concentration between the 2 groups ranged within the reference intervals and did not match the greater difference in PLP concentration. The 2 groups did also differ in tHcy levels, but the difference did not reach statistical significance (P=0.063). To evaluate a possible role for tHcy in the relationship between PLP and CRP values, we performed a general linear model analysis. As shown in Table 2, the strong association of PLP with CRP remained highly significant even after adjustment for tHcy (P<0.001). Conversely, after adjustment for PLP concentrations, the relationship between CRP and tHcy became clearly not statistically significant (P=0.571).

View this table: [in this window] [in a new window]   Table 1. Characteristics of the Framingham Heart Study Cohort According to CRP Levels

View this table: [in this window] [in a new window]   Table 2. Relationships Among Plasma tHcy, PLP, and CRP in the Framingham Heart Study Cohort

	Discussion

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These data demonstrate a strong association between decreased plasma PLP and increased levels of CRP, a major systemic marker of inflammation. Moreover, the association of PLP with CRP remained highly significant even after adjustment for tHcy, which is known to be an important metabolic indicator of vitamin B₆ status as well as a cardiovascular risk factor. Furthermore, the low vitamin B₆ levels were not attributable to impaired dietary intake, because it was similar in the 2 groups.

In a recent study, we also found a negative correlation between PLP and erythrocyte sedimentation rate, disease activity status, disease-related pain, joint swelling, and stiffness in patients with RA (E.-P. Chiang, PhD, et al, unpublished data, 2000). These results were consistent with data from similar studies.³ Furthermore, we demonstrated that the low PLP levels were not due to diminished vitamin B₆ intake, nor were they associated with increased urinary excretion of 4-pyridoxic acid, an end product of vitamin B₆ catabolism.

Despite the lack of a pathophysiological explanation for an association between PLP and markers of acute-phase status, a plausible interpretation of our data is that PLP is acting as a coenzyme for the inflammation-related functions. Because vitamin B₆ is integrally involved in the synthesis of nucleic acids and consequently in mRNA and protein synthesis, the production of cytokines and other polypeptide mediators during the inflammatory response might require an increased utilization of this coenzyme. This model is consistent with the observation that vitamin B₆ deficiency is associated with impairment in differentiation and maturation of monocyte-derived macrophages and T lymphocytes, inflammatory cells whose activation leads to the release of several enzymes and cytokines.²⁵ Vitamin B₆ deficiency was also reported to alter the regulation of interleukin-2 production.²⁶

The present study, moreover, confirms observations from others of a lack of association of increased CRP and tHcy levels,^{27 28} suggesting that the relationship between tHcy and atherosclerosis cannot be explained through a link with CRP per se, whereas both are independent risk factors for CVD.

Various conditions such as renal failure, smoking, and age are known to be associated with reduced levels of PLP. In addition, PLP, the predominant form of plasma vitamin B₆, is primarily bound to albumin, whose diminished levels may result in lower values of circulating PLP. Adjustment for albumin, creatinine, age, sex, and smoking, however, did not affect the observed association.

Indeed, additional studies are necessary to clarify whether inflammation-associated decreases in circulating PLP play a role in the cascade of metabolic events related to certain diseases. PLP is one of the most important coenzymes in maintaining the balance between protein synthesis and degradation. Therefore, it is likely that low levels of PLP may reflect a higher utilization of the coenzyme in an underlying inflammatory process, rather than a defective intake or excessive vitamin B₆ catabolism. The low circulating PLP seen as a possible indicator of an inflammatory status as well as a major determinant of tHcy levels may further our understanding of the mechanisms by which this metabolite acts as a risk factor for CVD.

	Footnotes

 
This material is based on work supported by the US Department of Agriculture under agreement No. 58-1950-9-001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture.

Received January 29, 2001; revision received March 20, 2001; accepted March 29, 2001.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. D’Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood. 1997;90:1–11.[Free Full Text]
   
2. Ueland PM, Refsum H, Beresford SAA, et al. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr. 2000;72:324–332.[Abstract/Free Full Text]
   
3. Roubenoff R, Roubenoff RA, Selhub J, et al. Abnormal vitamin B₆ status in rheumatoid cachexia: association with spontaneous tumor necrosis factor alpha production and markers of inflammation. Arthritis Rheum. 1995;38:105–109.[Medline] [Order article via Infotrieve]
   
4. Folsom AR, Nieto JF, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998;98:204–210.[Abstract/Free Full Text]
   
5. Robinson K, Arheart K, Refsum H, et al, from the European COMAC Group. Low circulating folate and vitamin B₆ concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. Circulation. 1998;97:437–443.[Abstract/Free Full Text]
   
6. Roubenoff R, Dellaripa P, Nadeau MR, et al. Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum. 1997;40:718–722.[Medline] [Order article via Infotrieve]
   
7. Rinehart JF, Greenberg LD. Arteriosclerotic lesions in pyridoxine-deficient monkeys. Am J Pathol. 1949;25:481–491.[Medline] [Order article via Infotrieve]
   
8. Levene CI, Murray JC. The aetiological role of maternal vitamin-B₆ deficiency in the development of atherosclerosis. Lancet. 1977;1:628–629.[Medline] [Order article via Infotrieve]
   
9. Is vitamin B₆ an antithrombotic agent? Lancet. 1981;1:1299–1300.[Medline] [Order article via Infotrieve]
   
10. Chi MS. Vitamin B₆ in cholesterol metabolism. Nutr Res. 1984;4:359–362.
    
11. Ross R, Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.[Free Full Text]
    
12. Pasceri V, Yeh ETH. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation. 1999;100:2124–2126.[Free Full Text]
    
13. Manzi S, Wasko MCM, Manzi S. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis. 2000;59:321–325.[Free Full Text]
    
14. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–843.[Abstract/Free Full Text]
    
15. Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165–2168.[Abstract/Free Full Text]
    
16. Bates CJ, Pentieva KD, Prentice A, et al. Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over. Br J Nutr. 1999;8:191–201.
    
17. Dawber TR, Moore FE, Mann GV. Coronary heart disease in the Framingham Study. Am J Public Health. 1957;47:4–24.
    
18. Selhub J, Jacques PF, Wilson PWF, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993;270:2693–2698.[Abstract]
    
19. Kannel WB, Wolf PA, Garrison RJ. Section 34: Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study 30-year follow-up. In: The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Springfield, Va: National Technical Information Service; 1987:1–459.
    
20. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly: the Framingham Heart Study. Arch Intern Med. 1987;147:1561–1564.[Abstract]
    
21. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1987;422:43–52.[Medline] [Order article via Infotrieve]
    
22. Tamura T, Freeberg LE, Cornwell PE. Inhibition by EDTA of growth of Lactobacillus casei in the folate microbiological assay and its reversal by added manganese or iron. Clin Chem. 1990;36:1993.[Medline] [Order article via Infotrieve]
    
23. Camp VM, Chipponi J, Farj BA. Radioenzymatic assay for direct measurement of plasma pyridoxal 5'-phosphate. Clin Chem. 1983;29:642–644.[Abstract/Free Full Text]
    
24. Rimm ED, Giovannucci EL, Stampfer MJ, et al. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol. 1992;135:1114–1126.[Abstract/Free Full Text]
    
25. Rall LC, Meydani SN. Vitamin B₆ and immune competence. Nutr Rev. 1993;51:217–225.[Medline] [Order article via Infotrieve]
    
26. Meydani SN, Ribaya-Mercado JD, Russell RM, et al. Vitamin B₆ deficiency impairs interleukin-2 production and lymphocyte proliferation in elderly adults. Am J Clin Nutr. 1991;53:1275–1280.[Abstract/Free Full Text]
    
27. Anderson JL, Muhlestein JB, Horne BD, et al. Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation. 2000;102:1227–1232.[Abstract/Free Full Text]
    
28. Becker A, Van Hinsberg VW, Kostense PJ, et al. Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and non-diabetic subjects: the Hoorn Study. Eur J Clin Invest.
    

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