Background/Purpose: In studies of SLE patients, the benefits of hydroxychloroquine (HCQ) extend beyond control of disease activity. In particular, HCQ use has decreased multiple cardiovascular risk factors (cholesterol and risk of diabetes) and reduced thrombosis in those with antiphospholipid antibodies. However, the amount of HCQ needed to obtain these benefits has not been ascertained. We asked whether blood HCQ levels were associated with cardiovascular risk benefit.

Methods: HCQ blood levels were measured by liquid chromatography-tandem mass spectrometry as described by Füzéry, et al (Clin Chim Acta 2013;421:79-84). We looked at the within-person relationship between HCQ blood concentration and three cardiovascular risk factors (systolic or diastolic blood pressure, cholesterol and glucose). To perform this analysis we calculated the mean HCQ blood level across each person. For each visit, we calculated the difference between the HCQ blood level at that particular visit and the patient’s mean. We then assessed whether there was a relationship between these differences and the patient’s cardiovascular risk factor level at a particular visit. The results indicate whether changes in HCQ blood concentration correspond to changes in cardiovascular risk factors.

Results: The association between changes in HCQ blood concentration and changes in cardiovascular risk factors is shown in Table 1.

Table 1. Association between changes in HCQ blood concentration and changes in cardiovascular risk factors.

We next looked to see whether increases in HCQ blood concentration among those with low levels (<500 ng/ml) had more of an effect than changes in the therapeutic range (500-1999 ng/ml). We also looked at changes in the super-therapeutic range (>2000 ng/ml). The results are in Table 2 below.

Table 2. Association between changes in HCQ concentration by ranges and changes in cardiovascular risk factors.

For cholesterol, a change of HCQ of 500 ng/ml in the sub-therapeutic range (i.e. an increase from 0 to 500 ng/ml) was associated with a relatively larger improvement in cholesterol (decline of 5.2 mg/dl). However changes in cholesterol in the HCQ therapeutic or super-therapeutic range were not associated with a decrease in cholesterol.

Conclusion: HCQ blood levels are statistically associated with blood pressure, cholesterol and glucose (proven for the first time). For cholesterol, the association is also meaningful clinically. The benefit is achieved when the HCQ blood level moves from 0 to 500 (low end of therapeutic range).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxychloroquine-blood-levels-are-significantly-associated-with-cardiovascular-risk-factors/