Abstract
Context: There is conflicting data on whether variations of physiologic cortisol levels associate with cardiovascular (CV) risk. Objective: We sought to reconcile prior discordant findings through utilization of a large sample size and selection of Framingham risk score to assess cardiovascular risk. An additional objective was to assess the relationship between caveolin-1 (CAV1) risk allele, cortisol levels, and CV risk given that CAV1 risk allele carriers have been associated with increased CV risk. Design & Participants: This was a cross-sectional study of 574 non-diabetic individuals who completed a common protocol that controlled for environmental factors. Data collection included fasting blood samples, blood pressure measurements, and a 24-hour urine free cortisol (UFC) collection. 517 of these participants also completed CAV1 genotyping. Main Outcome Measure: Subjects were classified as belonging to either the low-mode or high-mode urine cortisol groups, based on the bimodal distribution of UFC. Framingham risk score was selected as the main outcome measure to assess composite cardiovascular risk. Results: Framingham risk score was statistically higher in the high-mode cortisol group (10.22 ± 5.12) compared to the low-mode cortisol group (7.73 ± 7.08), p-value < 0.001. Framingham risk score was also statistically higher in the CAV1 risk allele carriers (8.91 ± 6.51) compared to CAV1 non-risk allele carriers (7.59 ± 6.88), p-value 0.034. Overall, the estimated effect of the risk allele was 1.33 ± 0.61, p-value 0.029. Conclusions: Higher, yet physiologic, levels of urinary cortisol are associated with increased cardiovascular risk.
