High Cardiovascular Risk but Poor Risk-factor Control in Antiphospholipid Syndrome — Worse in Primary APS than SLE-related APS

Highlights

– In a cross-sectional analysis of 1003 patients with antiphospholipid syndrome (APS) from 11 countries, traditional cardiovascular risk factors were common and control was generally suboptimal.

– Patients with SLE-related APS had higher prevalences of hypertension and hyperlipidaemia, but people with primary APS had worse attainment of several key cardiovascular risk-factor targets (blood pressure, smoking cessation, BMI, lipids).

– Older age and prior arterial thrombosis were associated with lower odds of meeting multiple cardiovascular risk targets. The findings underscore the need for systematic cardiovascular risk assessment and management in all APS patients, with particular attention to those with primary APS.

Background

Antiphospholipid syndrome (APS) is an autoimmune pro-thrombotic disorder defined by persistent antiphospholipid antibodies and clinical events such as venous or arterial thrombosis and/or pregnancy morbidity. APS occurs as a primary disorder or in association with systemic lupus erythematosus (SLE). Beyond the immediate thrombotic risk, people with APS carry an amplified long-term risk of atherosclerotic cardiovascular disease (ASCVD), likely attributable to a combination of antibody-driven endothelial dysfunction, thrombosis, and the influence of traditional cardiovascular risk factors.

International rheumatology and cardiology guidance emphasizes the importance of identifying and treating conventional cardiovascular risk factors in inflammatory and autoimmune disease states, because reduction of modifiable risk factors can materially lower ASCVD risk. In practice, however, the extent to which patients with APS achieve guideline-recommended targets for blood pressure, lipids, body mass index (BMI) and smoking cessation has been incompletely described across diverse health-care settings.

Study design

Overview

The SURF-SLE and APS project reported a cross-sectional audit of cardiovascular risk-factor prevalence and target attainment in 1003 adults with APS across 17 centres in 11 countries, covering 2015–2020 (with some centres extending data collection to 2022 because of the COVID-19 pandemic). Patients were eligible if they were aged ≥18 and met the revised Sapporo (Sydney) classification criteria for APS (Miyakis et al., 2006). Individuals meeting the 2012 SLICC criteria for SLE were classified as having SLE-related APS; those without SLE were classified as primary APS. Coexisting systemic autoimmune diseases other than SLE were excluded.

Measurements and endpoints

Cardiovascular risk-factor data were extracted from medical records. Risk was estimated using the Systematic Coronary Risk Evaluation (SCORE) algorithm. Target attainment for individual risk factors was assessed using contemporary European Society of Cardiology (ESC) recommendations for blood pressure and lipid targets, and by conventional thresholds for BMI and smoking cessation. The main outcomes were (1) prevalence of hypertension, hyperlipidaemia, obesity and current smoking, and (2) attainment of single and composite cardiovascular risk-factor targets. Analyses included unadjusted and adjusted mixed-effects logistic regression models to account for clustering by centre.

Key findings

Population characteristics

The study cohort comprised 1003 patients (78% women), median age 47 years (IQR 38–57) and median disease duration 11 years (IQR 5–18). Ethnicity was reported as White in 66% of 1000 individuals. Primary APS accounted for 54% (n=539) and SLE-related APS for 46% (n=464).

Prevalence of traditional cardiovascular risk factors

Traditional cardiovascular risk factors were common: hypertension in 41% (411/1003), hyperlipidaemia in 34% (344/1003), obesity in 32% (295/919 with recorded BMI), and current smoking in 19% (186/963 with smoking data). Compared with primary APS, SLE-related APS had a higher prevalence of hypertension (50% vs 33%; p<0·0001) and hyperlipidaemia (40% vs 30%; p=0·0009), but a lower prevalence of current smoking (16% vs 22%; p=0·012).

Guideline target attainment — single and composite outcomes

Overall, attainment of guideline targets was suboptimal across the cohort. Less than two-thirds of patients achieved blood pressure <130/80 mmHg when indicated, and control of LDL-cholesterol and BMI was frequently inadequate. Specifically, primary APS patients performed worse than SLE-related APS patients on several measures:

• Smoking cessation targets: lower attainment in primary APS (78%) than SLE-related APS (84%); p=0·012.
• Blood pressure <130/80 mmHg: 48% attainment in primary APS vs 57% in SLE-related APS; p=0·0067.
• Composite attainment of two or more cardiovascular risk-factor targets (smoking, BMI, blood pressure, LDL): worse in primary APS across the whole cohort and notably poorer in the high and very-high SCORE risk subgroups (including worse attainment for LDL, triglycerides, BMI and ≥3 targets).

Age and a history of arterial thrombosis were independently associated with lower odds of attaining three or more, or all four, prespecified cardiovascular risk-factor targets. These associations persisted in multivariable models adjusted for centre clustering.

Clinical and public health implications of the magnitude of the findings

The combination of high prevalence and poor control of major modifiable risk factors suggests a substantial preventable burden of ASCVD among people with APS. The divergence between primary and SLE-related APS — where patients with primary APS were less likely to meet several targets despite having somewhat lower measured prevalences of hypertension and hyperlipidaemia — points to possible gaps in risk recognition and management in primary APS populations. Clinicians may be more attuned to risk-factor management in people with SLE because of established care pathways, multidisciplinary follow-up, or differential prescribing of cardioprotective medications.

Expert commentary

The SURF-SLE and APS study fills an important knowledge gap by providing multinational real-world data on cardiovascular risk factors and target attainment in APS. Strengths include its large sample size, multicentre design, and use of standardized classification criteria (Miyakis et al., 2006; SLICC 2012). The use of mixed-effects models acknowledges practice variation across centres.

Limitations worth noting include the cross-sectional design (preventing causal inference), reliance on medical-record data with incomplete capture for some measures (e.g., BMI, smoking), and potential selection bias toward specialised centres that participated. Heterogeneity in local guideline implementation and in the years of data collection (2015–2022) may also influence observed target attainment. Finally, the study used the SCORE algorithm for risk estimation; SCORE has known limitations in younger populations and in people with autoimmune disease where risk can be under- or over-estimated depending on comorbidities.

Mechanistically, antiphospholipid antibodies are implicated in endothelial activation and accelerated atherothrombosis, providing biological plausibility for a synergistic effect with conventional risk factors. Therefore, aggressive control of modifiable risk factors is a rational strategy to reduce ASCVD events in APS. However, trial evidence specific to APS is lacking; extrapolation relies on large cardiovascular outcome trials in the general population and mechanistic rationale.

Current practice implications: clinicians should systematically screen for hypertension, dyslipidaemia, obesity and smoking in all people with APS. The study suggests that patients with primary APS are an overlooked group who may benefit from structured cardiovascular risk management pathways akin to those used for people with SLE.

Recommendations for practice and research

Clinical practice

• Implement routine cardiovascular-risk screening in APS clinics, including BP measurement, lipid profile, BMI and smoking assessment at regular intervals.
• Apply guideline-based targets for blood pressure and lipids tailored to measured cardiovascular risk, and consider lower LDL targets in those at high or very-high risk as per ESC guidance.
• Prioritise smoking cessation, weight management and appropriate pharmacologic therapy (antihypertensives, statins) where indicated; coordinate care with primary care and cardiology.

Research

• Prospective cohort studies to quantify incident ASCVD risk in APS phenotypes and to determine incremental risk contributed by antiphospholipid antibodies independent of traditional risk factors.
• Interventional trials testing strategies to improve risk-factor control in APS (for example, nurse-led clinics, integrated care pathways, or use of cardiovascular polypills) and their impact on cardiovascular events.
• Studies to define optimal risk-estimation tools in APS (modifications of SCORE or use of imaging biomarkers such as coronary artery calcium) to improve risk stratification and personalize therapy.

Conclusion

The SURF-SLE and APS multinational cross-sectional study demonstrates that traditional cardiovascular risk factors are frequent and poorly controlled in people with APS, with those having primary APS showing particularly poor attainment of key targets. Given the mechanistic plausibility of accelerated atherothrombosis in APS and the established benefit of risk-factor modification in the general population, these findings call for systematic cardiovascular risk assessment and proactive management in APS — including closer attention to primary APS where risk may be under-recognized.

Funding and clinicaltrials.gov

The study reported no funding. This was an observational audit and was not registered on clinicaltrials.gov.

References

1. Bolla E, Semb AG, Petri M, et al.; SURF-SLE and APS collaborators. Cardiovascular risk factor control in antiphospholipid syndrome, and differences between primary and systemic lupus erythematosus-related antiphospholipid syndrome (SURF-SLE and APS project): a cross-sectional study of 1003 individuals from 11 countries. Lancet Rheumatol. 2025 Nov 19: S2665-9913(25)00257-7. doi:10.1016/S2665-9913(25)00257-7. PMID: 41274305.

2. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.

3. Petri M, Orbai A-M, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–2686.

4. Conroy RM, Pyörälä K, Fitzgerald AP, et al. SCORE project: estimating ten-year risk of fatal cardiovascular disease in Europe. Eur Heart J. 2003;24(11):987–1003.

5. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104.

6. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188.

Image prompt for article thumbnail

A clinician reviewing cardiovascular charts of a middle-aged patient with APS in a modern clinic; visible icons for blood pressure cuff, lipid test results, and a crossed-out cigarette; diverse patient and clinician; clear, neutral colour palette, professional medical setting, focused composition.