Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.(Extended Report)

Background: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory.

Objective: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account.

Methods: HDL cholesterol and total cholesterol levels were determined in: (a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial).

Results: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity.

Conclusion: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.

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Mortality is increased in patients with rheumatoid arthritis (RA) compared with the general population, and cardiovascular disease is the most important cause of death. (1) Theoretically, this increased cardiovascular risk in patients with RA could be caused by (1) an increased prevalence of (known) risk factors for cardiovascular disease such as dyslipidaemia, diabetes mellitus, hypertension, body mass index, physical fitness, and smoking habits; (2) RA itself by either (a) the underlying inflammatory process, or (b) decreased functional capacity; and (3) undertreatment of cardiovascular disease as a comorbid condition in patients with RA (Boers M, unpublished data).

In this investigation we focused on dyslipidaemia. Published reports are sparse and contradictory about the levels of total, high density lipoprotein (HDL) and low density lipoprotein cholesterol, and triglycerides in patients with RA, even though there is some evidence for increased Lp(a) lipoprotein levels and lowered lipid levels in patients with active disease. (1)

Glucocorticoids are commonly used in patients with RA. Although it is well known that glucocorticoids induce hypercholesterolaemia, a well known cardiovascular risk factor, in patients with diseases other than RA, (2 3) the effect of (long term) glucocorticoid administration on lipid profiles in patients with RA is uncertain. Thus far a limited number of small scale studies have dealt with this subject in patients with RA, indicating either an increase or no effect of total cholesterol levels during (long term) glucocorticoid administration.

Therefore, in stored serum samples we investigated total cholesterol and HDL cholesterol levels cross sectionally, in patients with early RA (4) and in patients with longstanding, established disease. …