Impairment of quality of life in patients with antiphospholipid syndrome

Abstract

Objectives

Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history.

Methods

HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified.

Results

A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3).

Conclusion

Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient’s perspective and to provide patients with the support they need.

Keywords

Antiphospholipid syndrome arterial thrombosis MOS-SF-36 quality of life systemic lupus erythematosus

Introduction

Antiphospholipid syndrome (APS) is characterized by the association of thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPL).¹ APS can be considered as primary or associated to an underlying condition such as systemic lupus erythematosus (SLE).² APS patients are at high risk for thrombotic recurrences in the absence of an appropriate antithrombotic treatment.³ Health-related quality of life (HRQoL) is an important outcome in patients with chronic diseases.^4,5 While it has been clearly demonstrated that HRQoL is impaired in SLE,⁶ and in patients with history of venous thrombosis,^7–10 data are lacking in APS patients and it has been suggested that patients with either primary APS or SLE-associated APS had an impaired mental and physical health status.^11–13 However, it is unknown to what extent the presence of APS, in particular a thromboembolic history – either arterial or venous – has an impact on HRQoL impairment. Therefore, the objectives of our study were a) to compare the HRQoL of APS patients to the French general population norms, and b) to assess the impact of thromboembolic history (either arterial or venous) on HRQoL in APS patients.

Patients and methods

Study population

This multicentre study was an ancillary study of the case-control TAC(I)T program (Thrombotic risk in APS patients, activated protein C Insensivity and Thrombin generation). Participating centres were the Regional Competence Centre for Rare Vascular and Systemic Autoimmune Diseases (Nancy University Hospital, France), nine tertiary care centres (Besançon, Bordeaux, Brest, Dijon, Lille, Lyon, Reims, Saint-Etienne and Strasbourg) and one secondary care centre (Colmar). Between December 2006 and December 2009, consecutive patients were enrolled. Inclusion criteria were: a) age above 18 years, b) no anticoagulant therapy at inclusion, c) presence of aPL in plasma on two or more occasions at least 12 weeks apart,¹ or d) SLE (according to the American College of Rheumatology (ACR) revised criteria)^14,15 with (cases) or without (controls) a first episode of either arterial (e.g. stroke, myocardial infarction, peripheral arterial thrombosis), venous (e.g. pulmonary embolism, deep vein thrombosis) or small vessel thrombosis. History of obstetrical morbidity can be present in cases but not in controls. Pregnant patients were excluded.

Data collection

At inclusion, a full medical history and physical examination data were recorded. Baseline data included demographic information (age, sex), objectively documented APS (thrombotic, obstetrical events and aPL profile represented by either lupus anticoagulant (LA), anticardiolipin (aCL), or anti-β₂ glycoprotein-I antibodies (anti-β₂-GPI)) according to Sapporo/Sydney classification,¹ other features associated with APS (heart valve disease, livedo reticularis, thrombocytopenia, nephropathy, superficial vein thrombosis, neurological manifestations) and also thromboembolic and cardiovascular risk factors, medications, and inherited thrombophilia.

Definition of thrombotic events

Thrombotic events (arterial, venous, or small vessel thrombosis, in any tissue or organ) were confirmed by appropriate imaging workup. Thrombotic stroke was defined as a focal clinical neurologic event confirmed by neuroimaging studies such as computed tomography (CT) or magnetic resonance imaging. Acute myocardial infarction was defined as changes in a diagnostic electrocardiogram and increased levels of cardiac enzymes in the presence of typical symptoms such as chest pain and/or nausea, diaphoresis, or dyspnea. Pulmonary embolism was defined as positive result of ventilation/perfusion lung scan or spiral CT in the presence of typical symptoms, such as pleuritic chest pain, dyspnea, or hemoptysis. Deep vein thrombosis was defined by a symptomatic clinical event confirmed by compression ultrasonography. Small vessel thrombosis was defined as symptomatic events confirmed by an appropriate imaging (CT or magnetic resonance imaging) or histological techniques.

HRQoL assessment

HRQoL was assessed using the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. This tool is widely used to measure HRQoL in patients as well as in the general population.¹⁶ Of note, while the MOS-SF-36 questionnaire is a generic, reliable and valid measure for HRQoL and has been used in a variety of conditions including APS,^11–13 its validity and reliability in APS has not been assessed. The MOS-SF-36 questionnaire is self-administered and contains eight dimensions: bodily pain (BP), general health (GH), mental health (MH), physical function (PF), role-emotional (RE), role-physical (RP), social function (SF) and vitality (VT). A score from 0 (worse) to 100 (best) was calculated for each dimension of the MOS-SF-36. Two subscales were computed as two different weighted sums of dimension scores, i.e. a mental (MCS) and a physical component summary (PCS) score to obtain a mean of 50 with a standard deviation (SD) of 10 in a healthy general population.¹⁷ Higher scores represent a better HRQoL. Three scales (BP, PF, RP) correlate most highly with the physical component and contribute most to the scoring of the PCS measure. The mental component correlates most highly with the MH, RE, and SF scales, which also contribute most to the scoring of the MCS measure. Three of the scales (GH, SF, and VT) have noteworthy correlations with both components.

Statistical analysis

Description of data

Qualitative data were presented as numbers and percentages and were compared using Fisher’s exact tests. Quantitative data were presented as the mean with SD or median with interquartile range (IQR) and were compared using the non-parametric Wilcoxon test.

HRQoL analysis: Comparison to the French general population norms

Regarding French MOS-SF-36 norms, details of the national survey assessing HRQoL in the French general population have been published elsewhere:¹⁸ MOS-SF-36 was evaluated in 3617 French individuals (mean age was 49.6 ± 18.6 years old, female: 54%, non-responders: 1.18%). Seven age categories ranged from 18 to more than 74 years with 275 to 864 patients in each group. Cronbach’s coefficient ranged between 0.80 and 0.92, confirming the reliability of MOS-SF-36 in this population. MOS-SF-36 dimension scores were compared to the French population norms¹⁸ according to age groups and sex using a Student t-test. In addition to statistical significance of the tests, a difference of more than five points in one of the eight dimension scores was considered as clinically significant.^18,19 Because PCS and MCS weights had not been produced for the French norms, we did not use them for this comparison.

HRQoL analysis: Identification of characteristics associated with an impaired HRQoL

To assess the impact of clinical characteristics on HRQoL, all dimension scores as well as PCS and MCS scores were computed for different clinical variables and groups of patients. Firstly, univariate analysis identified all clinical variables associated with impaired HRQoL – defined as a lower PCS or MCS score. Then, we performed a multivariate analysis using multiple linear regression to identify independent variables. A p value < 0.05 was considered statistically significant. SAS 9.3 software (SAS Institute Inc, Cary, NC, USA) was used to perform analyses.

Ethics policy

This study was approved by the institutional regional review board (CPP III Est), and written informed consent was obtained from all participants.

Results

Patient characteristics at inclusion

Over a period of three years, 115 patients were included (mean age 42.7 ± 14.1 years old, 86 women): Thirty-six were aPL-positive patients without APS, 26 were SLE patients without APS and 53 patients had definite APS based on a history of one or more thrombotic manifestations (deep vein thrombosis and/or pulmonary embolism: n = 32; arterial thrombosis: n = 17; small vessel thrombosis: n = 5). Among SLE patients, mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 5 ± 7 (minimum–maximum: 0–26). A total of 113 HRQoL questionnaires were available and MCS and PCS were obtained in 111 patients. Patient baseline characteristics are described in Table 1.

Table 1

Patient characteristics at inclusion

Variable	Total (n = 115)
Mean age at inclusion, y ± SD	42.7	± 14.1
Women, n (%)	86	(74.8)
Risk factors, n (%)
Venous thromboembolism risk factors	15	(13.0)
Cardiovascular risk factors	62	(53.9)
Smoking	37	(32.2)
Hypertension	20	(17.4)
Hypercholesterolemia	18	(15.7)
Diabetes	4	(3.5)
BMI, kg/m²± SD	24.7	± 5.1
Obesity (BMI > 30 kg/m²)	15	(13.0)
Overweight (25 < BMI < 30 kg/m²)	28	(24.3)
History of vascular events (revised classification criteria for APS ^a ), n (%)
Vascular thrombosis^b	53	(46.1)
Venous thromboembolism (DVT and/or PE)	32	(27.8)
Arterial thrombosis	17	(14.8)
Small vessel thrombosis	5	(4.3)
Pregnancy morbidity^c	3	(5.9)
History of other features associated with APS ^a , n (%)
Livedo	19	(16.5)
Heart valve disease	8	(7.0)
Superficial vein thrombosis	7	(6.1)
Transient ischemic attack	4	(3.5)
Treatment
Aspirin	52	(45.2)
Steroids	22	(19.1)
Hydroxychloroquine	19	(16.5)
Laboratory parameters
Antiphospholipid antibodies
Lupus anticoagulant	64	(55.7)
Anticardiolipin antibodies	70	(60.9)
Anti-ß₂-glycoprotein I antibodies	14	(12.2)
Thrombopenia	11	(9.6)
Factor V Leiden mutation	11	(9.6)
Prothrombin mutation	8	(7.0)

y: years; APS: antiphospholipid syndrome; DVT: deep vein thrombosis; PE: pulmonary embolism; BMI: body mass index; SD: standard deviation.

According to Sydney criteria.¹

One patient had a history of both arterial and venous thromboses.

Among 51 pregnancies.

Comparison of HRQoL between patients and the French general population

Among these patients, all dimension scores – except for the PF dimension – were significantly lower than French general population norms (Supplemental Table 1).

HRQoL according to age

In comparison with the French general population norms, all HRQoL dimension scores were significantly impaired from the 25- to 54-year-old age groups. These impairments were also considered as clinically relevant based on a difference of more than five points. In patients aged 18 to 24 years, only three dimensions were significantly lower than in the general population (RP, GH, RE). In patients aged 55 to 64 years, SF, RE and MH were significantly lower while no difference of dimension scores was found between ages 65 to 74 years (Supplemental Table 1). Patients from 45 to 54 years old had the highest HRQoL impairment compared to the general population. PF, BP, VT and SF were significantly and dramatically impaired from age 25 to 54 years old, RP and GH from 18 to 54 years old, RE from 18 to 64 years old, and MH from 25 to 64 years old (Supplemental Figure 1).

Figure 1

Comparison of mean MOS-SF-36 dimension scores according to disease status.

HRQoL according to sex

Compared to the general population, HRQoL in men was significantly impaired in all dimension scores. In women, only GH, VT, SF, RE and MH dimensions were significantly lower than in the general population (Supplemental Table 1). For 25- to 34-year-old patients, more HRQoL dimensions were impaired in women than in men (all dimensions except SF in women and PF, RP, BP and GH in men). Furthermore, in 35- to 44-year-old patients, more HRQoL dimensions were impaired in men than in women (all dimensions in men and only BP, GH, MH dimensions impaired in women). These results suggest that an impairment of HRQoL began earlier in women than in men.

HRQoL according to disease status

Among 111 patients, mean PCS and MCS scores were 48.2 ± 8.9 and 43.1 ± 11.4, respectively, and were similar among APS or SLE patients (PCS = 46.9 ± 9.4 vs 46.8 ± 9.8; MCS = 40.0 ± 11.8 vs 42.2 ± 12.7, respectively). SLE-associated APS patients had the lowest PCS score in comparison with other groups of patients. MCS score was significantly different across groups (p = 0.01) and was the lowest in patients with primary or SLE-associated APS compared to other patient groups. Furthermore, the presence of both APS and SLE is associated with the worst HRQoL (Table 2).

Table 2

PCS and MCS scores according to diseases status

Diseases status	n (%)	Mean age ± SD	PCS score		MCS score
Diseases status	n (%)	Mean age ± SD	Mean ± SD	Median (IQR)	Mean ± SD	Median (IQR)
All APS patients	51 (46)	43.7 ± 13.7	46.9 ± 9.4	47.8 (42.9–52.5)	40.0 ± 11.8	42.3 (30.9–49.6)
All SLE patients	33 (30)	36.0 ± 10.3	46.8 ± 9.8	50.1 (41.6–53.4)	42.2 ± 12.7	45.6 (32.0–52.3)
Groups of patients
aPL patients without TE history	34 (31)	44.5 ± 15.1	49.9 ± 7.9	52.1 (45.1–55.7)	48.1 ± 8.5	48.7 (45.0–54.2)
Primary APS	44 (40)	44.7 ± 13	47.9 ± 8.9	47.8 (43.7–53.1)	39.9 ± 11.2	39.1 (31.4–49.0)
SLE-associated APS	7 (6)	37.1 ± 17.5	40.8 ± 10.6	43.3 (29.2–52.0)	40.6 ± 16.5	45.2 (27.0–52.5)
SLE patients with aPL without TE history	14 (13)	36.0 ± 10.3	48.5 ± 8.7	50.5 (44.7–54.6)	39.2 ± 12.6	39.2 (30.0–51.3)
SLE patients without aPL or TE history	12 (11)	40.3 ± 15.7	48.2 ± 10.2	51.7 (44.9–53.6)	46.6 ± 10.0	51.1 (37.5–54.2)

PL: antiphospholipid antibodies; APS: antiphospholipid syndrome; IQR: interquartile range; MCS: mental component summary; PCS: physical component summary; SD: standard deviation; SLE:systemic lupus erythematosus; TE: thromboembolic.

Regarding MOS-SF-36 dimensions (Figure 1), MH (p = 0.03), SF (p = 0.03), VT (p = 0.001) and GH (p = 0.04), were significantly different among groups of patients. SLE-associated APS patients seemed to be associated with the worst HRQoL scores in comparison with other patients. Furthermore, among SLE patients, a significant negative correlation was found between SLEDAI values and PF dimension only (R = 0.38, p = 0.03).

MOS-SF-36: Medical Outcomes Study Short-Form 36; aPL: antiphospholipid antibodies; APS: antiphospholipid syndrome; SLE: systemic lupus erythematosus; TE: thromboembolic. SF-36 dimensions: PF: physical function; RP: role-physical; BP: bodily pain; MH: mental health; RE: role-emotional; SF: social function; VT: vitality; GH: general health.

Impact of clinical variables on HRQoL impairment

Impact of cardiovascular risk factors on HRQoL impairment

Hypertension (p = 0.016), hypercholesterolemia (p = 0.031) and obesity (p < 0.001) were significantly associated with impaired PCS scores, and smoking was associated with impaired MCS scores (p = 0.028) (Supplemental Table 2).

Impact of clinical characteristics on HRQoL impairment

In APS patients with a history of arterial thrombosis compared to those without, HRQoL was dramatically impaired in all dimensions (Figure 2) and in both PCS and MCS scores (Table 3). In particular, a history of myocardial infarction was significantly associated with impaired PCS scores (p = 0.04) while peripheral arterial thrombosis was associated with impaired MCS scores (p = 0.02). Decreased MCS scores of patients with a history of ischaemic stroke did not reach statistical significance (p = 0.055). Other APS clinical classification criteria such as history of venous thromboembolism, of small vessel thrombosis or of pregnancy morbidity were not significantly associated with HRQoL impairment (Table 3).

Figure 2

Comparison of mean MOS-SF-36 dimension scores according to the presence of arterial thrombosis. MOS-SF-36: Medical Outcomes Study Short-Form 36; MOS-SF-36 dimensions: PF: physical function; RP: role-physical; BP: bodily pain; MH: mental health; RE: role-emotional; SF: social function; VT: vitality; GH: general health.

Table 3

Association between APS classification clinical criteria and PCS and MCS scores

		PCS score			MCS score
Variable	Patients, n	Mean ± SD	Median (IQR)	p value	Mean ± SD	Median (IQR)	p value
Venous thrombosis				0.55			0.72
No	80	47.7 ± 9.0	49.8 (43.2–54.1)		43.0 ± 11.9	45.8 (32.4–52.4)
Yes	31	49.5 ± 8.7	49.9 (44.3–55.5)		43.2 ± 10.1	44.3 (35.8–49.6)
Arterial thrombosis				0.003			0.004
No	95	49.2 ± 8.5	51.2 (44.7–54.7)		44.6 ± 10.3	46.0 (36.1–52.3)
Yes	16	42.2 ± 9.4	46.1 (33.2–48.1)		33.9 ± 13.7	33.8 (21.9–44.9)
Ischemic stroke ^a				0.20			0.055
No	103	48.4 ± 8.9	50.1 (43.3–54.4)		43.8 ± 11.0	45.7 (35.0–52.3)
Yes	8	45.1 ± 8.8	47.4 (40.5–49.0)		34.5 ± 13.7	36.2 (26.5–44.9)
Myocardial infarction ^a				0.04			0.55
No	108	48.6 ± 8.6	50.0 (44.2–54.3)		43.2 ± 11.4	45.4 (34.8–51.8)
Yes	3	34.5 ± 11.9	30.3 (25.4–47.9)		39.1 ± 13.3	38.1 (26.3–52.8)
Peripheral arterial thrombosis ^a				0.20			0.02
No	108	48.4 ± 8.9	50.0 (43.7–54.3)		43.6 ± 11.1	45.6 (35.3–51.9)
Yes	3	42.1 ± 10.3	47.8 (30.3–48.3)		25.9 ± 10.6	20.4 (19.3–38.1)
Other arterial thrombosis ^a				0.05			0.15
No	107	48.5 ± 8.9	50.0 (44.3–54.4)		43.5 ± 11.1	45.6 (35.6–51.8)
Yes	4	40.7 ± 8.4	43.2 (35.8–45.6)		32.4 ± 17.1	26.8 (20.9–43.9)
Small vessel thrombosis				0.16			0.14
No	106	48.5 ± 8.8	49.9 (44.1–54.4)		43.4 ± 11.4	45.6 (35.6–51.8)
Yes	5	42.2 ± 10.9	47.1 (33.3–50.8)		35.7 ± 10.4	32.0 (28.3–38.7)
Pregnancy morbidity				0.15			0.60
No	43	47.0 ± 8.7	47.9 (42.9–53.3)		45.0 ± 10.1	46.7 (39.5–51.4)
Yes	6	52.1 ± 10.8	54.8 (47.1–58.7)		42.0 ± 12.0	38.1 (32.0–56.4)

PL: antiphospholipid antibodies; APS: antiphospholipid syndrome; IQR: interquartile range; MCS: mental component summary; PCS: physical component summary; SD: standard deviation.

Each patient could have one or more thrombotic events.

Finally, when age, arterial thrombosis and any cardiovascular risk factors were entered in a multivariate model using multiple linear regression, arterial thrombosis remained the only independent factor significantly associated with an impaired PCS or MCS score.

Discussion

Our study clearly demonstrated that patients with APS had an impaired HRQoL in comparison with general population norms stratified by age and sex. Furthermore, our results showed that SLE-associated APS patients have the worst HRQoL in comparison with patients with aPL and/or SLE. Finally, we found that arterial thrombosis was associated with the worst HRQoL in APS patients.

The impact of aPL and APS on HRQoL has not been fully clarified yet. Costa et al. showed that primary APS patients had a lower HRQoL in comparison with healthy individuals.¹² Similarly, we confirmed that APS patients had an impaired HRQoL when results were compared with French norms stratified by age and sex. Balitsky et al. found that SLE patients with aPL without thrombosis had better PCS scores than APS or SLE patients with thromboembolic history.¹¹ Likewise, we have confirmed that asymptomatic aPL-positive patients had better HRQoL scores than patients with either APS or aPL and SLE. Furthermore, our results have shown that HRQoL in asymptomatic aPL patients was close to the mean score of a healthy general population.¹⁸ Finally, in this study, we found that APS patients have the worst HRQoL, especially those who have both APS and SLE, which is in line with another recent study.¹³

Whether the type of thromboembolic history influenced HRQoL has not been studied in APS patients previously. In the general population, a history of either arterial^20,21 or venous thrombosis is associated^7–10,22 with impaired HRQoL assessed by the MOS-SF-36. Because of the design of the study patients had either arterial or venous thrombosis and we were able to compare the two groups. Our results demonstrated important differences between the types of thrombosis in APS patients. Comparing all subscales of the MOS-SF-36 questionnaire to the French general population norms adjusted for age and sex, we identified a subset of young patients between 25 and 54 years old with a clinically significant impaired HRQoL mainly associated to a history of arterial thrombosis. A history of arterial thrombotic events dramatically impaired HRQoL independently of cardiovascular risk factors, which was not previously reported in this population. Myocardial infarction rather affected physical health more than other types of arterial thrombosis. These data are in line with previous results described above in a general population. Regarding mental dimensions, peripheral arterial disease and to a lesser extent stroke impaired HRQoL. Regarding history of venous thrombosis, the absence of reported HRQoL impairment may be due to the age of APS patients. While patients with a post-thrombotic syndrome in the general population appeared to have an impaired HRQoL,²³ it can be hypothesized that younger APS patients –who have experienced a venous thrombotic event – had not yet developed a severe post-thrombotic syndrome potentially affecting their HRQoL. The role of cardiovascular risk factors on HRQoL has been studied in the general population. It has been established that obesity,²⁴ smoking,^25,26 hypertension²⁷ and hypercholesterolemia²⁸ could lead to a decreased HRQoL and that risk factors had cumulative effects.²⁹ Our results did show that obesity, smoking, hypertension and hypercholesterolemia were associated with a lower HRQoL in the study population. Finally, even if age was different among groups of patients (e.g. APS or SLE patients), analyses were adjusted for age and confirmed the impact of thrombosis history on HRQoL impairment.

Some characteristics of our cohort may lead to possible limitations: First, we have included consecutive patients either with aPL/APS and SLE – two closely related disorders –³⁰ that reflected everyday clinical practice. Second, patients were not on oral anticoagulants at inclusion; thus, we measured only the burden of the disease and not that of anticoagulant treatment. Moreover, we may have selected less-severe patients than typical APS patients whose quality of life may even be lower. Finally, even if we found a correlation between HRQoL and lupus activity measured by the SLEDAI, we could not demonstrate that APS patients with mild SLE had better HRQoL compared to APS SLE patients with moderate or severe disease.

In conclusion, our study clearly demonstrates that APS patients have a dramatic impairment of their HRQoL compared to the general population. A history of arterial thrombosis was the main factor affecting HRQoL. Thus, we suggest that measurements of HRQoL should be included in everyday APS patient management to assess the burden of the disease from a patient’s perspective as well as an outcome criterion in therapeutic studies especially in clinical trials, together with classical endpoints such as recurrence of thrombosis and survival. Further studies should investigate the characteristics of HRQoL impairment in APS and specifically evaluate health interventions to improve patients’ perception of quality of life.

Footnotes

Acknowledgements

The authors wish to thank Alfousseyni Coly for his assistance in project coordinating and monitoring and Benoît-Damien Caritey for his assistance in statistical analysis.

Funding

This work was supported by grants from the Ministère Français de la Santé et des Sports (Programme Hospitalier de Recherche Clinique) (D.W., T.L.), the Fondation de France (D.W., T.L.), and the Région Lorraine (D.W., T.L.). The funding organizations are public institutions and had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Conflict of interest statement

The authors have no conflicts of interest to declare.

References

Miyakis

Lockshin

Atsumi

. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

Cervera

Piette

Font

. Euro-Phospholipid Project Group. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019–1027.

Cervera R, Serrano R, Pons-Estel GJ, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: A multicentre prospective study of 1000 patients. Ann Rheum Dis. Epub ahead of print 24 January 2014. DOI: 10.1136/annrheumdis-2013-204838.

Devilliers

Amoura

Besancenot

. LupusQoL-FR is valid to assess quality of life in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2012; 51: 1906–1915.

Rat

Pouchot

Fautrel

Boumier

Goupille

Guillemin

. Factors associated with fatigue in early arthritis: Results from a multicenter national French cohort study. Arthritis Care Res (Hoboken) 2012; 64: 1061–1069.

Khanna

Pal

Pandey

Handa

. The relationship between disease activity and quality of life in systemic lupus erythematosus. Rheumatology (Oxford) 2004; 43: 1536–1540.

Kahn

Hirsch

Shrier

. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002; 162: 1144–1148.

Kahn

M’Lan

Lamping

. The influence of venous thromboembolism on quality of life and severity of chronic venous disease. J Thromb Haemost 2004; 2: 2146–2151.

Kahn

Elman

Bornais

Blostein

Wells

. Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults. Thromb Haemost 2005; 93: 499–502.

10.

Kahn

Shbaklo

Lamping

. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost 2008; 6: 1105–1112.

11.

Balitsky

Peeva

. Thrombovascular events affect quality of life in patients with systemic lupus erythematosus. J Rheumatol 2011; 38: 1017–1019.

12.

Costa

Lage

da Mota

de Carvalho

. Fibromyalgia in primary antiphospholipid (Hughes) syndrome. Lupus 2011; 20: 1182–1186.

13.

Georgopoulou

Efraimidou

MacLennan

Ibrahim

Cox

. Antiphospholipid (Hughes) syndrome: Description of population and health-related quality of life (HRQoL) using the SF-36. Lupus 2015; 24: 174–179.

14.

Tan

Cohen

Fries

. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

15.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

16.

Alarcón

McGwin

Jr Uribe

. Systemic lupus erythematosus in a multiethnic lupus cohort (LUMINA). XVII. Predictors of self-reported health-related quality of life early in the disease course. Arthritis Rheum 2004; 51: 465–474.

17.

Ware

Jr Kosinski

Keller

. SF-36 physical and mental health summary scales: A user’s manual, Boston, MA: The Health Institute, New England Medical Center, 1994.

18.

Leplège

Ecosse

Pouchot

. Data from general population. In: Le questionnaire MOS SF-36: manuel de l'utilisateur et guide d'interprétation des scores [The MOS SF-36 questionnaire. User manual and interpretation guide scores], Paris: Estem, 2001, pp. 67–77.

19.

Ware

Snow

Kosinski

. SF-36 health survey manual and interpretation guide, Boston, MA: The Health Institute, New England Medical Center, 1993.

20.

Brown

Melville

Gray

. Quality of life four years after acute myocardial infarction: Short form 36 scores compared with a normal population. Heart 1999; 81: 352–358.

21.

Brown

Melville

Gray

Young

Skene

Hampton

. Comparison of the SF-36 health survey questionnaire with the Nottingham Health Profile in long-term survivors of a myocardial infarction. J Public Health Med 2000; 22: 167–175.

22.

van Korlaar

Vossen

Rosendaal

. The impact of venous thrombosis on quality of life. Thromb Res 2004; 114: 11–18.

23.

Cohen

Koopmans

Kremer Hovinga

. Potential for glomerular C4d as an indicator of thrombotic microangiopathy in lupus nephritis. Arthritis Rheum 2008; 58: 2460–2469.

24.

Lean

Han

Seidell

. Impairment of health and quality of life using new US federal guidelines for the identification of obesity. Arch Intern Med 1999; 159: 837–843.

25.

Wilson

Parsons

Wakefield

. The health-related quality-of-life of never smokers, ex-smokers, and light, moderate, and heavy smokers. Prev Med 1999; 29: 139–144.

26.

Laaksonen

Rahkonen

Martikainen

Karvonen

Lahelma

. Smoking and SF-36 health functioning. Prev Med 2006; 42: 206–209.

27.

Bardage

Isacson

. Hypertension and health-related quality of life. An epidemiological study in Sweden. J Clin Epidemiol 2001; 54: 172–181.

28.

Hyttinen

Kekäläinen

Vuorio

Sintonen

Strandberg

. Health-related quality of life in elderly patients with familial hypercholesterolemia. Int J Technol Assess Health Care 2008; 24: 228–234.

29.

Chambers

Guo

Siervogel

Hall

Chumlea

. Cumulative effects of cardiovascular disease risk factors on quality of life. J Nutr Health Aging 2002; 6: 179–184.

30.

Giannakopoulos

Krilis

. The pathogenesis of the antiphospholipid syndrome. N Engl J Med 2013; 368: 1033–1044.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.32 MB