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Cardiovascular RiskMarkers inPatients withManifest Atherosclerotic Complications 
Rajdl D.1, Rusňáková H.1, Pittrová H.1, Racek J.1, Polívka J.2, Ševčík P.2, Čechura M.3, Bartůňková V.4, Trefil L.1 

1Ústav klinické biochemie a laboratorní diagnostiky LF UK a FN Plzeň 2Neurologická klinika LF UK a FN Plzeň3Chirurgická klinika LF UK a FN Plzeň 4Kardiochirurgické oddělení FN Plzeň
 


Summary:

       Introduction: Several independent risk factors of cardiovascular diseases appeared recently. The aim of our study was to map frequency distribution of lipoprotein(a)[Lp(a)], ultrasenzitive C-reactive protein [uCRP] and homocysteine [Hcy] concentrations in patients with atherosclerotic complications. Subjects and methods: We analyzed total of 909 samples (622 men, 287 women). The venous blood serum was obtained from patients before reconstruction of lower limb arteries (262 samples, „surgery group“), before bypass operation of coronary arteries (366 samples, „cardio group“) and after cerebral ischemic attack (281 samples, „neuro group“).We determined concentrations of ultrasensitive CRP (uCRP; Orion Diagnostica), lipoprotein (a) (Lp(a);DAKO),total homocysteinelevels (Hcy,Abbott).We also determined levels of total cholesterol (TC;Human), HDL-cholesterol (HDL; Roche), triglycerides (TG; Human), apolipoproteins A-I and B (apoA, apoB; Tina-quant, Roche) and glucose. For statistical analysis we used descriptive statistic, unpaired t-test, analysis of variance (ANOVA) and correlations (Spearman’s coeficient). Computations were performed with StatView software. Results: More than 36% of patients showed increased (>0.3 mg/l) levels of Lp(a) and increased (>15 µmol/l) concentrations of homocysteine. About 56% of observed patients exceeded upper reference limit for uCRP [Table 1], 65% for TC (5.2 mmol/l) and 51% for TG (1.7 mmol/l). HDL was decreased (<1.0 mmol/l) in 22%. Women showed significantly higher concentrations of total and HDL-cholesterol and apoA than men (P<0.05, P<0.0001, P<0.001 resp.) and were older (P<0.0001) [Table 2]. There was a positive correlation between age and homocysteine concentration (P<0.0001, r = 0,34). Patients from „surgery group“ had significantly lower Lp(a) concentrations than patients form „neuro group“ (P<0.05) and non-significantly lower than cardio group (P = 0.075).However, „surgery group“ also showed significantly higher concentrations of uCRP than „cardio“ and „neuro group“ (P<0.001, P<0.05 resp.). All enrolled patients had one or more of measured risk factors. Further details are summarized in Table 3. Discussion: There is still no consensus on optimal values of new cardiovascular risk factors both for primary and for secondary prevention of atherosclerotic complications. The most contradictory opinions on normal reference values in healthy population and target values in secondary prevention remain in the case of homocysteine and uCRP. Upper reference limit for homocysteine is usually between 12 and 15 µmol/l (3), however, it is proposed that there is an increasing risk of cardiovascular diseases with increasing homocysteine levels without a clear treshold value (1). American Heart Association (AHA) recommends concentration of 10 µmol/l as a target value for people with increased risk of atherosclerotic complications (2). This condition was fulfilled only in 14 % of our patients. The prevalence of mild hyperhomocysteinaemia in the normal population is approximately 10–20 % (5), which is far lower than prevalence in our study (86%, cutoff 10 µmol/l). Supplementation of these high-risk patients with folic acid could be beneficial. C-reactive protein as a marker of development of atherosclerotic complications risk suffers from a pronounced intraindividual variability (29.9 %) (7). This makes determination of normal reference values and assesment of recommendations for clinicians more difficult. Riese et al. suggest repeated determination of uCRP whenever concentration exceeds 1.75 mg/l in men, 1.0 mg/l in women who do not use hormonal contraception and 2.0 mg/l in women using hormonal contraception (7). Our results are derived from a single measurement of CRP concentrations, however patients with concentrations of CRP grater than 10 mg/l were excluded. We used a reference interval values for apropriate age group and sex (8). More than 50 % of enrolled patients showed increased levels of CRP, however, patients before reconstruction of lower limb arteries had significantly higher levels than other 2 groups (before bypass operation of cardiac arteries, after cerebral ischemic attac) (Table 2). These patients could benefit from anti-inflammatory effects of statins and aspirine (4, 6). Conclusion: A great proportion of patients hospitalized for atherosclerotic complications have increased levels of homocysteine, uCRP and Lp(a). Homocysteine-lowering and anti-inflammatory drugs should become (besides of lipid lowering drugs) a regular part of secondary prevention of atherosclerotic complications.

        Key words: atherosclerosis, secondary prevention, risk markers.
       

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