Inflammatory predictors of mortality in the scandinavian simvastatin survival study

Abstract

SummaryBackground and hypothesis: The predictive value of specific markers of infection and autoimmunity for coronary events, such as the effects of statins on inflammation, is still controversial.Methods: A case-control design was used to compare Creactive protein (CRP) levels, seropositivity for Chlamydia pneumoniae and Helicobacter pylori, and anti-oxidized lowdensity lipoprotein (oxLDL) antibody levels in prerandomization blood samples from 129 participants in the Scandinavian Simvastatin Survival Study who died (cases), and from 129 matched participants who were alive during 5-year follow-up (controls).Results: Patients with CRP levels in the highest quartile had an increased risk of death compared with those in the first through third quartile (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.3-4.8). Seropositivity for Chlamydia pneumoniae or Helicobacter pylori and anti-oxLDL antibody levels were similar in cases and controls (p = NS). At a 4-month control, simvastatin reduced CRP levels (p = 0.009) while placebo did not (p = NS). However, the risk of death associated with high baseline CRP levels was similar in patients randomized to placebo (OR = 2.36, 95% CI 1.06-5.26) or simvastatin (OR = 3.13, 95% CI 1.06-9.21).

Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?

“…In a separate, open-label study, 1182 patients with known cardiovascular disease treated with pravastatin 40 mg/day showed a 13% reduction in CRP versus placebo [11]. Similarly, in a subpopulation of 129 secondary prevention patients enrolled in the Scandinavian Simvastatin Survival Study (4S) study, simvastatin reduced CRP levels significantly compared to baseline [12]. Reduction of CRP levels appears to be maintained long-term [10].…”

High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease

“…Even after adjustment for other risk factors, participants in the highest quartile of hs-CRP were 2 1 ⁄ 2 times more likely to die than those in the lower three quartiles (p = 0.005). 15 Recently reported post-hoc analyses from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) and Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trials suggest improved clinical outcomes in patients with lower versus higher hs-CRP levels after statin therapy, regardless of LDL cholesterol levels. 16,17 In PROVE IT, patients with acute coronary syndromes who had hs-CRP < 2 mg/dl after statin therapy had lower rates of recurrent cardiac events than did patients with higher levels (2.8 vs. 3.9 events per person years, p = 0.006), no matter the value of LDL cholesterol ( Fig.…”

A Rationale for Combined Therapy with a Calcium Channel Blocker and a Statin: Evaluation of Basic and Clinical Evidence

“…The effect of atorvastatin was also greater than that observed for other statins in previous large trials, such as Scandinavian Simvastatin Survival Study (4S) (Fig. 10) [105][106][107]. This is especially significant as levels of CRP represent an Fig.…”

“…(10). Comparison of change in median C-reactive protein from baseline to end point with different statins [102,[105][106][107].…”