Author + information
- Published online February 5, 2018.
- Qing Shang, PhD∗ (, )
- Hua Li, MM,
- Lai-Shan Tam, MD,
- Ching-Han Priscilla Wong, MD,
- John E. Sanderson, MD,
- Cheuk-Man Yu, MD and
- Brian Tomlinson, MD
- ↵∗Division of Cardiology, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Room 124010, 10/F, Lui Che Woo Clinical Science Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, N.T., Hong Kong
Cardiovascular disease is the most common cause of death in patients with psoriatic arthritis (PsA) (1). An overactive immune response in PsA together with traditional cardiovascular risk factors accelerates early atherosclerosis via a shared inflammatory pathway (2). Inflammation may also directly induce chronic myocardial injury with necrosis, apoptosis, and fibrosis. Our previous studies have shown early evidence of thickened and stiffened ventricular walls, increased diastolic filling pressure, and subclinical left ventricular (LV) systolic dysfunction (3–5). However, all these findings were obtained in the resting state. This study aimed to determine whether impaired cardiovascular reserve on exercise is a more sensitive indicator of myocardial injury in patients with PsA and whether this relates to cumulative inflammatory burden.
Sixty patients with PsA and 27 healthy control subjects (50.1 ± 10.0 years vs. 50.4 ± 10.0 years; female/male, 24/36 vs. 11/16) were recruited for a low-level bicycle exercise echocardiography beginning at a workload of 25 W with only 1 increment of 25 W to 50 W after 3 min. Exclusion criteria were uncontrolled severe hypertension, significant atrial or ventricular arrhythmia, significant valvular diseases, significant coronary artery disease, prior history of myocardial infarction, impaired LV systolic function (ejection fraction <50%, or any regional wall motion abnormality), or inability to exercise. To assess LV longitudinal functional reserve, the early diastolic (E′) and systolic (S′) mitral annular velocities were assessed and LV diastolic (ΔE′ × [1 - (1/E′resting)]) and systolic (ΔS′ × [1 - (1/S′resting)]) longitudinal functional reserve indices were derived, where ΔE′ and ΔS′ were the change of E′ and S′ from resting to 25 W or 50 W, respectively.
Patients in this study had a mean age at PsA diagnosis of 40.8 ± 10.6 years and disease duration of 9.2 ± 8.4 years. Disease Activity Score in 28 joints, Psoriasis Area and Severity Index, and inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein) were assessed. During the previous 1 year, inflammatory markers were raised ≥3 times in 83% of patients and ≥4 times in 50% of patients. Although ESR (21.3 ± 16.6 mm/h vs. 13.3 ± 8.0 mm/h; p = 0.027) and C-reactive protein (median 1.65 vs. 0.6 mg/dl; p < 0.001) were significantly higher in patients than in control subjects, 75% of patients had inactive disease (Disease Activity Score in 28 joints, ≤3.2) during recruitment. Fifty-three patients (88.3%) had psoriasis with median Psoriasis Area and Severity Index equal to 2.4. Seventeen (28.3%) patients had hypertension or diabetes mellitus and 1 (1.7%) had obesity.
Compared with control subjects, patients with PsA had a trend toward an increased LV wall thickness (0.86 ± 0.16 cm vs. 0.79 ± 0.15 cm; p = 0.053), and LV volumes (end-diastolic: 85.1 ± 17.4 ml vs. 77.8 ± 13.7 ml, p = 0.058; end-systolic: 31.4 ± 8.3 ml vs. 27.8 ± 6.2 ml, p = 0.051) in spite of a comparable LV ejection fraction (63% vs. 64%). However, the LV functional reserve on exercise, demonstrated by ΔE′ and ΔS′ and LV longitudinal reserve indices, was significantly lower in patients than in control subjects (Figure 1). Moreover, the 1-year cumulative average of ESR (ESRcum = area under curve/duration) was negatively correlated with ΔS′ (r = −0.394; p = 0.004) and LV longitudinal systolic reserve index (r = −0.403; p = 0.003) at the 50-W stage of exercise even after adjusting for diabetes mellitus and hypertension. In addition, the current inflammatory level (ESR and Ln [C-reactive protein]) and disease activity (Disease Activity Score in 28 joints) were also negatively correlated with ΔS′ and LV longitudinal systolic reserve index (p < 0.05).
This study is an extension of previous research works and strengthens the relationship between inflammation and myocardial involvement, which can be detected by a low-level exercise protocol. Most of patients in this study had the disease for a long time, nearly one-third of patients had diabetes mellitus or hypertension, and the patient group showed signs of subclinical myocardial remodeling. Although 75% of patients had inactive disease at the time of study, the early impaired longitudinal function at rest and blunted myocardial reserve on exercise indirectly suggest that previous low-level inflammatory activation with intermittent flare-ups (indicated by the cumulative inflammatory burden) can lead to sustained subclinical myocardial remodeling and impaired myocardial function and reserve on exercise.
The authors thank Prof. Edmund K. Li for his kind help, and thank Ms. Skiva Chan, Mr. Isaac Cheng, Ms. Pearl Ho, Ms. Dico Tse, Ms. Ka-Bik Lai, Ms. Carria Zhang, Mr. Ken Wong, Ms. Xueting Wang, Mr. Xero Lau, Dr. Tracy Zhu, Dr. Jiayun Shen, Dr. Jing Wang, Dr. Xiuxia Luo, Ms. Ava Cheung, Ms. Tena Li, Ms. Queenie Mak, and Ms. Wendy Yeung for their assistance.
Please note: This study was funded by the Health and Medical Research Fund (#02130686) from the Food and Health Bureau of Hong Kong, Hong Kong, China. Dr. Tomlinson has received grant/research funding from Amgen, AstraZeneca, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, and Roche; is a consultant/adviser to Amgen, AstraZeneca, Merck Serono, and Sanofi; and is on the Speakers Bureau for Amgen, Merck Serono, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (https://www2.ccrb.cuhk.edu.hk/registry/public/243).
- 2018 American College of Cardiology Foundation
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