Shared genetic factors between osteoarthritis and cardiovascular disease may underlie common etiology

Abstract

Osteoarthritis is one of the most common musculoskeletal diseases and increases the risk of severe cardiovascular disease, like heart attack and stroke. In some individuals, osteoarthritis and cardiovascular disease will co-occur. This co-occurrence might be due to shared risk factors, for example high age, lifestyle factors and/or a shared genetic liability for the two diseases. Here, we show that the correlation between osteoarthritis and cardiovascular disease can be explained by shared genetic factors, independent of high age and body weight, and also likely independent of lifestyle factors, like smoking and physical activity level. Findings suggest that genetic factors that are shared for osteoarthritis and cardiovascular disease may contribute to both diseases. Thus, the prevailing idea that osteoarthritis is predominantly a risk factor for cardiovascular disease is challenged. Our findings imply that the current diagnostic boundaries between these diseases may need to be re-evaluated.

Fig. 1. Phenotypic correlations between site-specific OA and any type of severe cardiovascular disease.

Phenotypic correlations (black bars, i.e. correlations between hip osteoarthritis (OA) and knee OA, respectively, and severe cardiovascular disease in one individual) with 95% confidence interval, and parts of this correlation that are explained by additive genetic factors, common- and unique environmental factors. Analyses are performed separately by joint site, on 29 985 twin pairs, where 145 had any site OA (hip, knee and/or hand OA) and any of CVDs, 38 had hip OA and any of CVDs and 44 had knee OA and any of CVDs (pair level). Please note that the total correlation (denoted with black bars) can be lower than the sum of A and C components, when the E component has negative value. Data are presented as correlations +/− 95% confidence intervals. Source data are provided as a Source Data file.

Fig. 2. Phenotypic correlations between any site OA and each of specific types of severe cardiovascular disease.

Phenotypic correlations (black bars, i.e. correlations between osteoarthritis and specific, severe cardiovascular disease (CVD) in one individual) with 95% confidence interval, and parts of this correlation that are explained by additive genetic factors, common- and unique environmental factors. Analyses are performed for any site OA (hip, knee and/or hand OA) combined with specific CVDs on 29 985 twin pairs, i.e. where 39 had cardiac arrythmias and any site OA, 49 had CHD and any site OA, 15 had heart failure and any site OA, and 18 had stroke and any site OA (pair level). Please note that the total correlation (denoted with black bars) can be lower than the sum of A and C components, when the E component has negative value. CHD: coronary heart disease. Data are presented as correlations +/− 95% confidence intervals. Source data are provided as a Source Data file.

Fig. 3. The cumulative incidence of bivariate concordance for OA and CVD.

The cumulative incidence of bivariate concordance for OA and CVD from the start of follow-up (time 0, Jan 1^st 1997) until the second twins get the last diagnosis of OA or CVD (event). MZ: monozygotic, DZ: dizygotic. Data are presented as the cumulative incidence +/− 95% confidence intervals. Source data are provided as a Source Data file.