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Inflammatory markers, their relation to maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation (AF), and the effect of candesartan were investigated in a double-blind placebo-controlled study (CAPRAF). One hundred seventy-one patients with persistent AF were randomly assigned to receive candesartan 8 mg/day or placebo for 3 to 6 weeks before and candesartan 16 mg/day or placebo for 6 months after electrical cardioversion. Serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha, interleukin-6, P-selectin, E-selectin, CD-40 ligand, and vascular cell adhesion molecule-1 were measured at baseline and end of study. Compared with patients with a relapse of AF, patients still in sinus rhythm at 6 months after cardioversion (n = 40) had lower baseline hs-CRP and E-selectin levels: median 2.36 mg/L (25th, 75th percentiles 1.28, 4.09) versus 3.44 mg/L (25th, 75th percentiles 1.66, 6.05, p = 0.031) and 32 ng/ml (25th, 75th percentiles 23, 42) versus 37 ng/ml (25th, 75th percentiles 28, 51, p = 0.042), respectively. Neither sustained sinus rhythm for 6 months nor treatment with candesartan had an impact on measured concentrations of markers of inflammation. In conclusion, low hs-CRP and E-selectin at baseline were associated with maintenance of sinus rhythm after electrical cardioversion.

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.

Antagonists of the renin-angiotensin system, such as angiotensin type 1 (AT(1)) receptor inhibitors and angiotensin-converting enzyme inhibitors, are becoming increasingly popular agents in treating patients with systemic hypertension and minimizing organ damage. In the present study, we compared the effects of eprosartan, an AT(1) receptor inhibitor, with the diuretic hydrochlorothiazide in a group of newly diagnosed hypertensive patients with multiple risk factors for atherosclerosis. The subjects were monitored and tested at 0 and 4 weeks to determine their individual effects on vascular and inflammatory markers. Although blood pressure reduction was comparable between the 2 agents, there were notable differences in their effects on markers of inflammation and oxidation. We observed a 28% reduction in neutrophil superoxide anion generating capacity, a 34% reduction in soluble monocyte chemotactic protein-1, and a 35% reduction in soluble vascular cell adhesion molecule with eprosartan therapy (all p <0.05 from the start of therapy). In addition, eprosartan showed further benefit in its ability to increase low-density lipoprotein oxidation lag time, suggesting an increased resistance to oxidation and/or modification of low-density lipoprotein. Although hydrochlorothiazide was effective in blood pressure reduction, there were no significant changes in any of the above parameters after 4 weeks of treatment. These findings suggest that eprosartan, an AT(1) receptor inhibitor, effectively reduces systemic blood pressure and, compared with hydrochlorothiazide, suggests additional benefits in the vasculature by inhibiting mechanisms of inflammation and oxidation.

To investigate the effect of estrogen with antioxidant potential on soluble markers of chronic vascular inflammation, we administered either transdermal 17beta-estradiol 0.1 mg/day (9 women) or 17beta-estradiol 0.1 mg and medroxyprogesterone acetate 2.5 mg/day (11 women) for 1-month treatment in a randomized design, with measurement of cell adhesion molecules. Hormone therapy significantly lowered intercellular adhesion molecules-1 levels by 8% (p = 0.009) and tended to lower E-selectin levels (by 6%, p = 0.096), and VCAM-1 levels (by 4%, p = 0.084).