Modifiable Cardiovascular Risk Factors in Adults with Sickle Cell Disease
Authors: Ogunsile Foluso Joy , Stewart Kerry , Wang Hang , Lanzkron Sophie 
Published: October 2019

Abstract
Introduction:
Body composition, cardiorespiratory fitness (CRF) and muscular strength(MusS) are important predictors of cardiovascular (CV) mortality and morbidity. Poor CRF, body composition and MusS are each associated with higher rates of musculoskeletal injury, inflammation, heart disease, and all-cause mortality. Fortunately, these parameters in the general population, are partly influenced by lifestyle habits and can improve with modifying unhealthy behaviors such as increasing activity levels. Few studies have examined fitness parameters, in particularly MusS, in adults with sickle cell disease (SCD). As cardiopulmonary disease is a leading cause of death in SCD, we sought to better characterize fitness and body composition in adults with SCD. The objective of this study is to describe modifiable CV risk factors of fitness along with other risk factors of smoking, hypertension, and cholesterol in a population of adults with SCD.
Methods:
Forty-six participants (ages 21-66 yrs.; 74% female; sickle cell anemia n =29, sickle variant genotype n=17) were recruited from a comprehensive adult sickle center. Non-pregnant adults in steady-state SCD disease without an absolute contraindications to exercise were eligible to participate. CRF was measured using symptom-limited exercise testing performed on a cycle ergometer following an incremental ramp protocol. Maximal oxygen uptake (VO2 max), a key measure of CRF, was calculated during exercise testing. MusS was assessed using an isokinetic dynamometer, the Biodex system 3, the gold standard to measure MusS in rehabilitative medicine. Peak isokinetic torques of knee extension and flexion were determined at 60 degrees per second, and adjusted for body weight on the Biodex system 3. A medical history, fitness assessments, anthropometric testing, and laboratory testing were completed on all SCD participants. Sixteen SCD participants had dual energy x-ray absorptiometry imaging to assess fat, lean, and bone mass. The remaining 30 SCD patients underwent isokinetic CRF and MusS testing. Lean muscle mass and body fat of participants were compared to US national guidelines, VO2max was compared to predicted norms. As there are no well-established normative values for MusS, we compared values to a cohort of 60 adults without SCD (age 21-40 yrs.; 63% female) who underwent MusS testing as a part of a separate study. For muscle strength, multivariate regression was performed to control for the effects of age, BMI, gender, and SCD status on peak torques.
Results:
All SCD and control participants were able to complete testing safely without any adverse events. 34.7% of SCD participants (n=16) had a smoking history with a mean pack year history of 9 years (Table 1). 18% of participants (n=10) received medical treatment for hypertension (Table 1). 64% (n=32) of participants had reduced HDL levels and 8% (n=3) had elevated triglycerides. Median (IQR) waist-hip circumference (F=0.89(0.14), M=0.93 (0.11)) and total percent body fat (F=37.7(11.5), M=22.3(11.5)) for SCD participants were higher than national normative values and 66% were classified as obese (Table 1). SCD participants had reduced mean (SD) VO2max, 16.77 (3.29) and 19.56 (7.27) ml/min/kg for females and males respectively compared with norms. In 90% of SCD participants (n=28), percent-predicted VO2max was less than normal (i.e. < 84 percent-predicted) with 4 adults having markedly reduced VO2max with a percent-predicted value less than 50%. Hemoglobin, hydroxyurea use and SCD genotype were not predictive of VO2max. Compared to controls, mean (SD) peak torque values for knee extension (82.7 Nm (19) vs 44.33 Nm (18.85), p<0.0001) and flexion ( 38.6 Nm (9.03)vs 19.19 Nm (13.2), p<0.0001) at 60 degrees were lower in SCD participants even after adjusting for age, sex, and body mass index (BMI) (Table1).
Limitations: Study limitations include a small sample size, and the lack of controls matched for race, age, BMI, and hemoglobin.
Conclusion:
In this pilot study we show that both CRF and MusS are decreased in adults with SCD. Additionally, this cohort had a number of CV risk factors including smoking, hypertension and reduced HDL levels. As we know these are important predictors of poor CV outcomes additional research is needed to determine whether a carefully designed exercise and diet program can improve these modifiable CV risk factors and ultimately health status in adults living with SCD.

Disclosures
Wang: PCORI: Research Funding. Lanzkron:Pfizer: Consultancy, Research Funding; NHLBI: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; GBT: Consultancy, Research Funding; Selexys: Research Funding; Prolong: Research Funding.