MOL/200087; Total nos of Pages: 3;
MOL 200087
Editorial comment
Therapy and clinical trials Asim K. Duttaroy
Department of Nutrition, Faculty of Medicine, University of Oslo, Norway
Correspondence to Professor Asim K. Duttaroy, Department of Nutrition, Institute
for Basic Medical Sciences, University of Oslo, POB 1046 Blindern, N-0316 Oslo,
Norway
Tel: +47 22 85 15 47; fax: +47 22 85 13 41; e-mail: a.k.duttaroy@medisin.uio.no
Current Opinion in Lipidology 2006, 17:000–000
Abbreviations
CHD
CRP
CVD
ICAM-1
MCP-1
PAD
VCAM-1
coronary heart disease
C-reactive protein
cardiovascular disease
intercellular cell-adhesion molecule 1
monocyte chemoattractant protein 1
peripheral arterial disease
vascular cell adhesion molecule 1
ß 2006 Lippincott Williams & Wilkins
0957-9672
Epidemiological and clinical studies have shown strong
and consistent relationships between markers of inflammation and risk for cardiovascular disease (CVD) [1].
Recent studies support a central role for inflammation
in all phases of the atherosclerotic disease process, from
lesion initiation to progression and, ultimately, to plaque
rupture and the ensuing thrombotic disorders of CVD
[2]. One approach to study of inflammation and CVD is
through measurement of circulating inflammatory markers. Several biomarkers linked to inflammation and
atherogenesis have been identified. Monocyte chemoattractant protein 1 (MCP-1), produced by endothelial
and smooth muscle cells, is a CC chemokine that mediates monocyte recruitment and entry into vessel walls at
sites of atherosclerosis [3]. Although a large number of
studies in vitro have focused on the potential role of
MCP-1 in pathogenesis, there are no prospective population-based studies investigating the relationship
between plasma MCP-1 levels and subclinical atherosclerosis or incidence of coronary heart disease (CHD).
Hoogeveen et al. [4] investigated the relationship
between MCP-1 level and CHD in a large, prospective,
population-based study. In this study, 209 cases with
lower-extremity peripheral arterial disease (PAD) and
412 cases with an incidence of CHD were compared
with 733 and 709 subjects without PAD and CHD,
respectively. Individuals with PAD had significantly
higher levels of MCP-1 compared with the group without
PAD. They also observed elevated levels of C-reactive
protein (CRP) in the plasma of those who also had higher
plasma levels of MCP-1. However, more clinical studies
are required to assess whether intervention targeting
MCP-1 is beneficial in the treatment of atherosclerosis.
CRP is an acute-phase protein that is produced in
response to acute injury, infection or other inflammatory
stimuli. CRP has been shown in prospective cohort and
case-control studies to be a reliable measure of underlying systemic inflammation and a strong predictor of
future cardiovascular events [5–7]. These observations
stimulated interest in a possible role for CRP in CVD risk
assessment in clinical practice [5–7]. Although most
studies have shown that CRP is a strong and independent
predictor of atherosclerotic risk, the recent study by
Wilson et al. [8] showed that the elevated CRP level
did not provide any further prognostic information
beyond traditional risk-factor assessment to predict
future major CHD in a prospective, observational cohort
study. They used a total of 1949 men and 2497 women
without CVD from the Framingham study who underwent CVD risk-factor assessment.
Obesity contributes to the occurrence of atherosclerotic
and hypertensive disease and it is now considered to be a
serious health problem, especially in the industrialized
world. Panagiotakos et al. [9] observed an association
between inflammation and obesity status in a populationbased sample of 3042 adults without CVD. They
observed several inflammatory markers to correlate with
central adiposity, irrespective of age, sex, or various
metabolic or life-style variables.
Hall et al. [10] examined whether administration of
isoflavones reduces endothelial inflammation in postmenopausal women. In contrast to previous findings,
these workers did not find any beneficial effects of
supplementation of isoflavones on plasma levels of
intercellular cell-adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, or
MCP-1. However, plasma CRP levels were reduced in
these women after isoflavone supplementation. They
observed that the effects of isoflvaone supplementation
depend on the genotype of the woman. Analysis of key
selected genotypes in this population of postmenopausal women indicated a significant diet–gene interaction
for isoflavones between the ERb AluI genotypes. Isoflavones reduced plasma VCAM-1 in the variant AA
genotype but not in the homozygous wild-type (GG)
or heterozygous (GA) genotypes. It seems that certain subpopulations may respond more beneficially to
isoflavone supplementation by decreasing plasma
VCAM-1 levels in one genotype of the ERb AluI polymorphism.
1
MOL/200087; Total nos of Pages: 3;
2 Bimonthly update
References
1
Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med 1999; 340:
115–126.
2
Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr
2006; 83:456S–460S.
3
Cushing SD, Berliner JA, Valente AJ, et al. Minimally modified low density
lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells
and smooth muscle cells. Proc Natl Acad Sci U S A 1990; 87:5134–5138.
4
Hoogeveen RC, Morrison A, Boerwinkle E, et al. Plasma MCP-1 level and risk
for peripheral arterial disease and incident coronary heart disease: Atherosclerosis Risk in Communities study. Atherosclerosis 2005; 183:301–307.
5
Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation aspirin, and the risk
of cardiovascular disease in apparently healthy men. N Engl J Med 1997;
336:973–979.
6
de Maat MP, Trion A. C-reactive protein as a risk factor versus risk marker.
Curr Opin Lipidol 2004; 15:651–657.
7
Ridker PM, Cushman M, Stampfer MJ, et al. Plasma concentration of Creactive protein and risk of developing peripheral vascular disease. Circulation
1998; 97:425–428.
8
Wilson PW, Nam BH, Pfencina M, et al. C-reactive protein and risk of
cardiovascular disease in men and women from the Framingham Heart Study.
Arch Intern Med 2005; 165:2473–2478.
9
Panagiotakos DB, Pitsavos C, Yannakoulia M, et al. The implication of obesity
and central fat on markers of chronic inflammation: the ATTICA study.
Atherosclerosis 2005; 183:308–315.
10 Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and
markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr 2006; 83:592–
600.
MOL/200087; Total nos of Pages: 3;
Therapy and clinical trials Duttaroy 3
Recommended reading
Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and markers
of lipid and glucose metabolism in postmenopausal women: interactions with
genotype and equol production. Am J Clin Nutr 2006; 83:592–600.
This study did not find any beneficial effects of supplementing isoflavones on
circulating concentrations of ICAM-1, VCAM-1, E-selectin, or MCP-1 in postmenopausal women. Analysis of key selected genotypes in this population of postmenopausal women indicated a significant diet–gene interaction for isoflavones
between the ERb AluI genotypes with isoflavones reducing plasma VCAM-1 in the
variant AA genotype but not the homozygous wild-type or heterozygous genotypes.
Hoogeveen RC, Morrison A, Boerwinkle E, et al. Plasma MCP-1 level and risk for
peripheral arterial disease and incident coronary heart disease: Atherosclerosis Risk in Communities study. Atherosclerosis 2005; 183:301–307.
This paper provides data supporting the general hypothesis that increased
expression of MCP-1 is part of an inflammatory system which plays a critical in
the etiology of atherosclerosis through increased recruitment of mononuclear
leucocytes to sites of vascular injury. In this study, 209 cases with lower-extremity
PAD and 412 cases with incident of CHD were compared with 733 and 709
subjects without PAD and CHD, respectively. Individuals with PAD had significantly higher levels of MCP-1 compared with the group without PAD.
Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr
2006; 83:456S–460S.
This paper suggests that inflammation is central to the progression from fatty
streak to complex plaque. The author suggests that assessment and management
of CVD risk must evolve in step with a greater understanding of pathophysiologic
mechanisms. Inflammatory markers such as CRP merit careful consideration for
inclusion in our risk-assessment algorithms. Roles of inflammation in the initiation
and development of atherosclerosis are now increasingly recognized in treating
CVD patients.
Panagiotakos DB, Pitsavos C, Yannakoulia M, et al. The implication of obesity and
central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 2005; 183:308–315.
The authors observed an association between the inflammation process and
central obesity status in a population-based sample of 3042 adults without CVD.
Wilson PW, Nam BH, Pencina M, et al. C-reactive protein and risk of cardiovas
cular disease in men and women from the Framingham Heart Study. Arch
Intern Med 2005; 165:2473–2478.
This paper demonstrates that elevated CRP level did not provide any further
prognostic information, beyond the traditional risk-factor assessment, predicting
future major CHD in a prospective, observational cohort study.
MOL
Manuscript No. 200087
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