Statin drugs, serum cholesterol, and prostate-specific antigen in the National Health and Nutrition Examination Survey 2001-2004

Abstract

Purpose: We evaluated the associations of statins and serum cholesterol with PSA to understand whether the inverse associations of statins and low cholesterol with aggressive prostate cancer are explained by detection bias.

Methods: We analyzed data from 2,574 men aged > or =40 years without prostate cancer in The National Health and Nutrition Examination Survey 2001-2004. We estimated multivariable-adjusted geometric mean PSA by statin use and cholesterol quintiles. To limit the influence of correlates of statin use and cholesterol on PSA, we stratified by comorbidities.

Results: Statin users had a non-statistically significantly lower PSA than non-users (0.90 vs. 0.95 ng/mL, p = 0.22), especially in men without comorbidities (n = 1,680; 0.86 vs. 0.99 ng/mL p = 0.02). In men with comorbidities, statin users had a non-statistically significantly higher PSA than non-users (0.91 vs. 0.83 ng/mL, p = 0.14). Men with lower cholesterol had lower PSA (bottom vs. top quintile: 0.92, 1.02 ng/mL, p-trend = 0.06).

Conclusion: Statin users and men with lower cholesterol may have lower PSA. If so, the probability of detecting asymptomatic prostate cancer might be lower at present, but these cases might be more likely to be diagnosed at an advanced stage in the future. Thus, PSA-associated bias is unlikely to explain the inverse association of statins with advanced prostate cancer.

Figure 1

This figure illustrates the asociations that would be observed between statin use and localized and advanced stage prostate cancer if statin use either increased or decreased PSA concentration. t₀ = Development of asymptomatic tumor at same stage and grade for all scenarios. PSA = PSA screening test = PSA screening test when PSA concentration reached the level for referral for biopsy

Figure 2

In this scenario, we assume that statin drug use has no influence on the development of advanced prostate cancer. Note that if comorbid statin users were compared to comorbid men who do not use a statin (as in Table 3), the apparent state might be different. t₀ = Development of asymptomatic tumor at same stage and grade for all scenarios. PSA = PSA screening test = PSA screening test when PSA concentration reached the level for referral for biopsy