Gender Differences In CRP Studies
Sunday, 22 March 2009 00:00
The Tromsø Study, a prospective, population-based ultrasound study, investigated how HDL cholesterol relates to carotid plaque progression. This study showed that a high level of HDL cholesterol reduces plaque growth in subjects with preexisting carotid atherosclerosis. Transformation of the plaque mass into higher echogenicity is associated with reduced growth. HDL cholesterol was thought to stabilize plaque and counteract its growth by reducing the lipid content and inflammation. Although plaque area increased in 70% of cases, and most plaque became more echogenic during the follow-up interval, the plaque that became more echolucent grew more in size than those that became more echogenic (Circulation 2005; 112498-504).
The evolution toward more echolucent or echogenic plaque was studied in women and men in the follow-up of the Tromsø Study. Both genders with carotid plaque had significantly elevated levels of white blood cells (WBC) and fibrinogen, but not CRP, as compared to subjects without plaque. All inflammatory markers were significantly associated with plaque area in men. WBC was significantly associated with plaque echogenicity in women, whereas no association was found between fibrinogen and CRP and plaque echogenicity in either gender. The study showed gender differences in associations between measures of carotid atherosclerosis and inflammatory markers. CRP did not discriminate echolucent from echogenic carotid plaque in either gender. There is still a need to better understand the gender differences on the correlation between atherosclerosis and inflammation (Cerebrovasc Dis 2009; 27:392-397).
CRP levels are higher in obese subjects and it seems to be linked to increased insulin resistance. Interventions that alter insulin resistance, such as weight loss, exercise, and conjugated linoleic acid, also alter CRP. Glycemic load is associated with CRP, but there have been no interventions with altered macronutrient composition. Alcohol lowers CRP, but the mechanism is unknown. The interaction between gender and obesity needs further understanding, but it appears that obesity has a greater effect on CRP levels in women (Curr Atheroscler Rep 2003; 5:431-6). Further laboratory epidemiologic data link inflammation and high-sensitivity CRP (hs-CRP) to insulin resistance: hs-CRP levels have been associated with impaired insulin sensitivity and the development of dysglycemic conditions, including the cardiometabolic syndrome and incident type 2 diabetes. hs-CRP has also been associated with each of the individual components of the cardiometabolic syndrome. Furthermore, in large prospective studies, hs-CRP adds prognostic information about cardiovascular risk beyond that provided by the cardiometabolic syndrome. These findings have led to discussion about the addition of hs-CRP measurement to the current definition of the cardiometabolic syndrome to improve detection of risk for both diabetes and cardiovascular events in patients. Multiple clinical studies are needed to evaluate whether agents traditionally used to improve glycemic control may also significantly reduce hs-CRP (J Cardiometab Syndr 2006; 1:190-6).
The relationship between HDL-cholesterol levels and various inflammation markers status in a sample of cardiovascular disease free adult men and women from Greece (the ATTICA Study) has been studied. In an apparently healthy population aged over 18 years old and adherent to the Mediterranean diet, 46% of men and 40% of women had total serum cholesterol levels > 200 mg/dl, while 21% of men and 7% of women had HDL-cholesterol levels < 35 mg/dl. HDL-cholesterol levels were inversely correlated to the hs-CRP levels (b = -0.028, P = 0.001) and homocysteine levels (b = -0.039, P = 0.036), after adjustment for sex, age, body mass index, physical activity status, smoking, total cholesterol levels, lipid lower agents, ethanol intake and diabetes mellitus; while no statistical significance was found between HDL-cholesterol levels and interleukin-6 and serum amyloid-a. This study among others illustrates the emerging anti-inflammatory role of HDL-cholesterol in reducing cardiovascular risk (Int J Cardiol 2007; 122:29-33).
Clinically significant seasonal variation in hs-CRP was observed in healthy adults: women had greater seasonal variation than men, (14% vs 6% fluctuation) between late spring and late fall, respectively. Some factors can be further studied to explain the observed seasonal variation of hsCRP: relative plasma volume, anthropometric measurements, and diastolic blood pressure. However more attention should be paid in the clinical setting to these seasonal variations (Clin Chem 2009; 55:313-21).
Common genetic variants in the CRP gene were substantially and independently associated with plasma hs-CRP concentrations in a large multiethnic case–control study of postmenopausal women. These associations may differ with ethnicity. Further studies will be warranted to confirm the ethnic differences in CRP gene variants and the potential direct role of these genetic variants on the risk for type 2 diabetes mellitus (Clin Chem 2009; 55: 351-60). Mexican-American women had a higher adjusted CRP concentration, measured with a high-sensitivity assay, than did white women. African-American women had a higher age-adjusted geometric mean concentration than white women, but the difference was no longer significant after adjustment for potential confounders. The higher CRP concentrations among Mexican-American women than white women could indicate that Mexican-American women are at increased risk for cardiovascular disease, especially if their risk functions for cardiovascular disease are similar to those of other women (Clin Chem 2004; 50: 574-81).
Despite improved understanding of athero-thrombosis, cardiovascular prediction algorithms for women have largely relied on traditional risk factors. Now, gender differences are taken into consideration in the developing of risk scores for CVD. The predictive value of hs-CRP (greater than that of traditional laboratory markers such as total cholesterol, HDL cholesterol, and LDL cholesterol and novel markers such as lipoprotein (a), homocysteine, and apolipoproteins AI and B as described by Nader Rifai et al. Clin Chem 2001; 47: 403-11) indicated to these authors the importance and need to develop and validate cardiovascular risk algorithms for women (JAMA 2007; 297:611-19) and later, men (Circulation 2008; 118:2243-51), based on a large panel of traditional and novel risk factors. The Reynolds Risk Score in the Assessment of Global Cardiovascular Risk showed highly improved accuracy of two clinical algorithms for global cardiovascular risk prediction that reclassified 40% to 50% of women at intermediate risk into higher- or lower-risk categories (JAMA 2007; 297:611-19).
March 22, 2009
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