Low Levels of LDL May Increase Cardiovascular Disease Risk

illustration of artery clogged with cholesterol plaque
illustration of artery clogged with cholesterol plaque
Patients with rheumatoid arthritis and having low-density lipoprotein levels were found to be at a high risk for cardiovascular disease, according to data collected from the combination of 4 large studies.

Patients with rheumatoid arthritis (RA) who have low circulating low-density lipoprotein concentrations (LDL-C) had high coronary arterial calcium scores, according to a study published in Arthritis and Rheumatology.

Researchers compiled data from 4 cohort studies to analyze the levels of coronary arterial calcium scores between patients with RA and patients in a control group at all strata of circulating lipids. All patients completed self-reported demographics, anthropometric measurements, fasting blood analysis, cardiac computed tomography, and coronary arterial calcium score calculation.

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Of the 546 patients with RA, 21% were men, 81% were white, and the average age was 56 years old. Of the 5279 healthy controls, 48% were men, 38% were white, and the average age was 61 years old. Patients with RA had a lower mean adjusted circulating low-density lipoprotein concentration and a higher prevalence of hypertension, mean adjusted coronary arterial calcium score, and mean adjusted c-reactive protein level (P <.001, for all) when compared with the healthy controls.

For patients with RA, a circulating low-density lipoprotein concentration <70 mg/dL was associated with a mean adjusted coronary arterial calcium score 3-fold higher than the score of healthy controls with the same strata of low-density lipoprotein concentration (18.6 vs 4.6 Agatston units; P <.001). When analyzing the subgroup of white participants who had ever smoked, patients with RA in the lower strata of circulating low-density lipoprotein had a mean adjusted coronary arterial calcium score 10-fold higher than comparable healthy controls (61.2 vs 5.7 units; P <.001).

Limitations of this study include variations in the protocols of the 4 included cohort studies, the demographic differences between the patients with RA and the healthy controls, and some loss of statistical power in subgroup analysis due to smaller sample size.

The researchers concluded that patients with RA and low concentrations of low-density lipoproteins are at a higher risk for cardiovascular disease (CVD) events due to their higher coronary arterial calcium scores. Furthermore, they concluded that the “data support the so-called ‘lipid paradox’ in which RA patients with similarly low LDL-C levels have been noted to be at unexpectedly high risk for CVD events and suggest a susceptible subgroup of RA patients that may be appropriate for additional CVD screening and/or preemptory aggressive primary prevention efforts targeting non-lipid risk factors.”


Giles JT, Wasko MCM, Chung CP, et al. Exploring the lipid paradox theory in rheumatoid arthritis: associations of low circulating low density lipoprotein concentration with subclinical coronary atherosclerosis [published online March 18, 2019]. Arthritis Rheumatol. doi: 10.1002/art.40889