LDL Cholesterol, BMI May Be Linked to Risk for Osteoarthritis

Cholesterol build-up
Cholesterol build-up
Data show a causal association between lower LDL cholesterol and increased risk for osteoarthritis.

Recent data published in Arthritis & Rheumatology provide evidence of a causal role of lower low-density lipoprotein cholesterol (LDL-C) and higher body mass index (BMI) in osteoarthritis (OA).

The study included participants from the Malmo Diet and Cancer Study (MDCS) (n=27,691) and participants from the UK Biobank (n=376,435) were used to replicate any novel findings.

The researchers used trait-specific polygenic risk scores for LDL-C and high-density lipoprotein cholesterol (HDL-C), triglycerides, BMI, fasting plasma glucose, and systolic blood pressure to test associations of genetically predicted elevations in each trait with incident OA diagnosis (n=3559), OA joint replacement (n=2780), or both (total OA; n=4226) in Mendelian randomization analyses in MDCS participants. They used self-reported or hospital-diagnosed OA data of participants from the UK Biobank (n=65,213).

Of participants from MDCS, the results indicated that genetically predicted higher LDL-C was associated with a lower risk for OA diagnosis (odds ratio [OR], 0.83; 95% CI, 0.73-0.95) and total OA (OR, 0.87; 95% CI, 0.78-0.98). These results were supported by multivariable Mendelian randomization for OA diagnosis (OR, 0.84; 95% CI, 0.75-0.95) and total OA (OR, 0.87; 95% CI, 0.78-0.97) and conventional 2-sample Mendelian randomization for OA diagnosis (OR, 0.86; 95% CI, 0.75-0.98).

The researchers also found that genetically predicted higher BMI was associated with an increased risk for OA diagnosis (OR, 1.65; 95% CI, 1.14-2.41), although Mendelian randomization with Egger regression indicated pleiotropic bias and larger association with OA diagnosis (OR, 3.25; 95% CI, 1.26-8.39), OA joint replacement (OR, 3.81; 95% CI, 1.39-10.4), and total OA (OR, 3.41; 95% CI, 1.43-8.15).

The researchers did not find any associations between OA outcomes and genetically predicted HDL-C, triglycerides, fasting plasma glucose, or systolic blood pressure.

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When the researchers studied participants from the UK Biobank, they were able to replicate the LDL-C associations.

“This evidence challenges the current perspectives from epidemiological studies and indicates that future investigations need to focus on the mechanisms linking lower [LDL-C] with OA pathogenesis to potentially identify therapeutic targets, and on investigating how the widespread use of [LDL-C] lowering drugs may impact the pathogenesis of OA and related outcomes,” the researchers wrote.

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Hindy G, Akesson KE, Melander O, et al. Cardiometabolic polygenic risk scores and osteoarthritis outcomes: a Mendelian randomization study from the Malmo Diet and Cancer Study and the UK Biobank [published online January 7, 2019]. Arthritis Rheumatol. doi:10.1002/art.40812