Risk factors for coronary heart disease and acute-phase proteins. A population-based study

Abstract

Aims Circulating levels of C-reactive protein and serum amyloid A protein increase markedly, and albumin levels fall, during the acute-phase response to tissue injury, infection and inflammation. Some acute-phase proteins have been associated with increased risks of coronary heart disease in long-term prospective studies. The aim of the present study was to determine whether circulating concentrations of C-reactive protein, albumin and serum amyloid A protein are correlated with one another, standard vascular risk factors, markers of persistent infection, or indicators of socio-economic status. Methods and ResultsWe report a cross-sectional study of 704 individuals without a history of coronary heart disease from five general practices in Bedfordshire, U.K. Plasma levels of C-reactive protein and serum amyloid A protein were strongly associated with each other (2P<0·00001) and inversely related to levels of serum albumin (2P<0·00001). There were highly significant associations of plasma C-reactive protein concentrations with cigarette smoking and obesity (2P<0·00001 for each). Serum albumin levels were strongly associated with blood pressure (2P<0·0001) and plasma lipids (2P<0·001), and concentrations of serum amyloid A protein were strongly correlated with obesity (2P<0·0001). ConclusionPreviously reported long-term prospective studies have found an increased risk of coronary heart disease of about 50% in people with raised baseline levels of plasma C-reactive protein or low albumin. The strong cross-sectional associations we have found between levels of these proteins with each other and with concentrations of serum amyloid A protein suggest that some underlying process related to inflammation is likely to be of relevance to the causation of disease. Further studies are needed to determine if the strong associations of plasma levels of C-reactive protein with cigarette smoking and obesity indicate that this particular protein can mediate some of the effects of those risk factors on coronary heart disease. (Eur Heart J 1999; 20: 954-959)

Genetic and environmental contributions to plasma C-reactive protein and interleukin-6 levels – a study in twins

“…However, after adjustment for all confounding covariates, estimated heritability for CRP was substantially lower (Vogel-Motulsky heritability coefficient 0.22, 95% confidence interval [À0.16-0.61]), pointing to a moderate genetic influence on the observed variability (Table 4). Similar to previous studies, 6,10,15,19,[21][22][23][24]31,44 CRP levels were strongly influenced by factors such as female gender (Po0.0005), older age (Po0.0005) or the BMI (Po0.0001). Particularly, the BMI, which has a large degree of heritability, 55,56 was significantly associated with higher plasma CRP levels in a linear multiple regression analysis.…”

“…[16][17][18] In addition, it is known that (environmental) factors such as obesity, older age, female gender, smoking, diabetes mellitus, chronic infections, lower socio-economic status, greater alcohol consumption and medications such as oral contraceptives are involved in a low-grade inflammatory response with elevated plasma CRP levels. 6,[19][20][21][22][23][24][25][26] An aim of determining plasma CRP levels could be related to polymorphisms in upstream cytokines such as interleukin (IL)-6. 13,27 IL-6 induces CRP production in hepatocytes and it is the only cytokine that can stimulate the synthesis of all other acute-phase proteins.…”

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

“…2,[17][18][19] As mentioned, there are diverging reports regarding the roles of obesity and insulin resistance in influencing the production of CRP. The circulating levels are elevated in obesity, 8,20 particularly when adipose tissue is centrally deposited, 2 as indicated by a high waist-hip ratio. 7,21 The levels correlate positively with body fat in nondiabetic Pima Indians 22 and are high in people with type 2 diabetes.…”

“…28 Furthermore, the increase in CRP and other inflammatory markers, such as IL-6, was not fully explained by BMI in impaired glucose tolerance and type 2 diabetes. 29 The acute-phase protein SAA correlates positively with obesity 8 and is higher in people with type 2 diabetes mellitus and impaired glucose tolerance than in non-diabetic controls. 23,29 Male subjects with coronary heart disease (CHD) have markedly higher SAA levels than those without CHD 30 and SAA may, due to its interaction with HDL-cholesterol, be a factor in the accelerated atherosclerosis of diabetes.…”

“…5 Cytokines are not only produced by inflammatory cells in damaged tissues but are also secreted from adipocytes, 6 making obesity a confounding factor in the association between acute-phase proteins and cardiovascular disease. 7,8 There are diverging reports regarding the importance of obesity per se and insulin resistance for driving the increase in inflammatory markers. In a study of CRP, IL-6 and TNF-a in healthy women and women with polycystic ovary syndrome, obesity and not insulin resistance was found to be the major determinant of the inflammatory markers.…”