Total hip arthroplasty, osteolysis and cardiovascular disease in patients with osteoarthritis of the hip

The pathogenesis of OA and CVD is currently related to inflammatory processes. It is unknown how OA and its surgical treatment impact the cardiovascular system.

Hypotheses: We hypothesized that (1) THA patients more than 5 years after the index surgery have an increased risk for cardiovascular morbidity and mortality compared with the general population and (2) that late cardiovascular risk following THA may be mediated by the development of osteolysis and systemic inflammation. Furthermore, we hypothesized that patients with asymptomatic osteolysis after THA (3) are more likely to develop CVD and (4) have a higher burden of cardiovascular risk markers than patients without periacetabular osteolysis.

Aims of the studies: The general aim of this thesis was to investigate patients treated with THA due to OA and patients treated with THA who subsequently underwent revision surgery and the associated risk of cardiovascular morbidity and mortality. Further aims were to compare patients with and without periacetabular osteolysis regarding CVD and cardiovascular risk markers. The specific aims were as follows. Paper I) to determine whether there is a late correlation between THA and cardiovascular events; Paper II) to compare patients after revision surgery due to aseptic loosening of the implant to controls (patients not having revision surgery) regarding the risk for cardiovascular morbidity and mortality and the time to first event during the exposure period; Paper III) to investigate whether THA patients with asymptomatic periacetabular osteolysis have an increased long-term risk of CVD compared to THA patients without osteolysis and the time to event; Paper IV) to compare THA patients with and without periacetabular osteolysis regarding cardiovascular risk markers and electrocardiography findings.

Materials and methods/results: Paper I. This was a nationwide, matched cohort study with data on 91,527 OA patients who underwent surgical treatment. Data were obtained from the Swedish Hip Arthroplasty Register. A control cohort consisting of 270,688 patients from the general Swedish population was matched at a ratio of 1:3 to each case by sex, age, and residence. The mean follow-up time was 10 years. Patients with surgically treated OA of the hip had an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Paper II. This was a nationwide, nested, case-control study consisting of 14,430 patients undergoing cemented THA due to OA between the years 1992 and 2005. The case group consisted of 2,886 patients who underwent reoperation on the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (11,544). Patients with OA who underwent THA and subsequently underwent revision surgery due to loosening had a higher risk of developing cardiovascular events than controls. Paper III. This was an observational cohort study of 139 patients who underwent uncemented THA between 1992 and 2007. All patients were assessed by CT of the affected hip to sort patients into 2 groups, those with periacetabular osteolysis (cases=33) and those without periacetabular osteolysis (controls=106). There was a higher rate of CVD among THA patients with periacetabular osteolysis than among THA patients without periacetabular osteolysis but no statistically significant risk increase. Paper IV. This was a cross-sectional study consisting of 108 patients who underwent THA (uncemented components) due to OA between 1992 and 2007. All patients were assessed by CT of the affected hip. Patients with periacetabular osteolysis constituted the cases (n=19) patients without periacetabular osteolysis (n=89) were selected as controls.(89) Markers of inflammation, risk markers for CVD and ECG abnormalities were collected and compared between the groups. There was no difference in the risk burden for CVD many years after THA between patients with and without periacetabular osteolysis.

Conclusions: Patients with surgically treated OA of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation. Patients who undergo revision surgery due to aseptic loosening and/or osteolysis have a higher risk of developing cardiovascular events. These observations may be indicative of common disease pathways. Furthermore, while the risk for CVD in patients with periacetabular osteolysis is slightly higher, there is no significant difference in the risk burden for CVD compared with patients without periacetabular osteolysis. The examination of a larger sample and the use of comparable durations after surgery are recommended.

List of scientific papers

I. Gordon M, Rysinska A, Garland A, Rolfson O, Aspberg S, Eisler T, Garellick G, Stark A, Hailer NP, Sköldenberg O. Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty: A Nationwide Cohort Study. Medicine (Baltimore). 2016 Feb;95(6):2662.
https://doi.org/10.1097/MD.0000000000002662

II. Rysinska A, Sköldenberg O, Garland A, Rolfson O, Aspberg S, Eisler T, Garellick G, Stark A, Gordon M. Aseptic loosening after total hip arthroplasty and the risk of cardiovascular disease: A nested case-control study. PLoS One. 2018 Nov 14; 13(11):e0204391.
https://doi.org/10.1371/journal.pone.0204391

III. Rysinska A, Aspberg S, Hailer NP, Hallman D, Laurencikas E, Eisler T, Gordon M, Sköldenberg O. Asymptomatic Osteolysis as a Risk Factor for Cardiovascular Disease-A prospective observational cohort study. [Manuscript]

IV. Rysinska A, Aspberg S, Hailer NP, Eisler T, Gordon M, Sköldenberg O. Cardiovascular and Inflammatory Markers in Patients with and without Periacetabular Osteolysis after Total Hip arthroplasty-A cross sectional study. [Manuscript]