Traditional and nontraditional risk factors associated with CVD and SLE.
Risk factor
Comments
References
Traditional risk factors
Hypertension
(i) It is more frequent among SLE patients than people with noninflammatory disorders (ii) It acts as CVD subphenotype as well as a risk factor and also influences the risk of death by CVD. It increases the risk of thrombosis and it is more prevalent among SLE patients with atherosclerotic plaque. (iii) Lupus patients with abnormal myocardial scintigraphic findings and hypertension, as risk factor for CAD, had a higher risk of abnormal findings on coronary angiography.
(i) T2DM has influence on abnormal myocardial perfusion in asymptomatic patients with SLE. (ii) Alterations in glycemic profile were associated with traditional risk factors for CHD and lupus characteristics, including CVD, damage index, and renal involvement. (iii) Patients with SLE and T2DM were at increased risk of thrombosis, atherosclerotic plaque, and CAC. This risk remains elevated throughout the course of the disease.
(i) The main risk factor for death in SLE was heart involvement, which was influenced by dyslipidemia. The inflammatory context of SLE leads to dysregulation of lipid metabolism pathways increased risk of atherosclerotic disease and thrombotic events. (ii) Alterations in lipid profile were a risk factor for endothelial dysfunction, myocardial perfusion abnormalities, and premature CAC and CAD in young women.
(i) Male gender was a risk factor for developing severe organ damage (CVD) and mortality in SLE patients. (ii) Males with SLE were at increased risk of thrombosis and CAC. This risk remains elevated throughout the course of the disease. (iii) Patients had more peripheral vascular and gonadal involvement.
(i) SLE patients had a high prevalence of MetS that directly contributes to increasing inflammatory status and oxidative stress. (ii) MetS were associated with traditional risk factors for CAD and lupus characteristics, including CVD, damage Index, and renal involvement. (iii) HCQ use proved to be protective against MetS. (iv) Insulin sensitivity and intima-media thickness are altered in SLE patients, especially those with MetS comorbidity with an associated increase in disease activity and damage (v) Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients
(i) Patients with SLE who had excess weight present distinct clinical-laboratory findings, sociodemographic characteristics, and treatment options when compared to normal weight patients. Excess weight is associated with SLE poor prognosis. (ii) Increased weight has influence on abnormal myocardial perfusion in asymptomatic SLE patients. (iii) SLE patients with high BMI have increased QT interval parameters, presence of CAD, and carotid plaque. This prolongation may lead to an increased CV risk.
(i) Smoking is an important determinant in the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events in SLE patients, due to atherosclerotic plaque and thrombosis (ii) Smoking habits influence abnormal myocardial perfusion in asymptomatic SLE patients. (iii) Smoking was a risk factor for premature CAC and CAD in young women with SLE.
(i) High percentage of SLE patients with abnormal angiographic findings was in postmenopausal status. (ii) There is high prevalence of premature menopausal status as risk factor for CVD. (iii) Postmenopausal status was a risk factor for premature CAC in young women with SLE. (iv) Postmenopausal women had a higher prevalence of subclinical AT and abnormal myocardial perfusion in asymptomatic patients with SLE.
(i) Familial history of CVD was an independent risk factor for atherosclerotic process and premature CAC in women with SLE. (ii) Family history of CVD influences abnormal myocardial perfusion in asymptomatic SLE.
HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but data suggest its use may be safe if APLA are not present or vascular arterial events have not previously occurred.
(i) Hyperhomocysteinemia was a risk factor for CAC in SLE patients. (ii) The presence of polyautoimmunity and hyperhomocysteinemia was a risk factor for thrombotic events.
There are several differences regarding clinical (including CVD), prognostic, socioeconomic, educational, and access to medical care features in GLADEL cohort according to ancestry (White, Mestizo, and African-LA).
(i) A SNP in FGG rs2066865 demonstrated association with arterial thrombosis risk in Hispanic American patients with SLE. (ii) The CRP GT20 variant is more likely to occur in African-American and Hispanic SLE patients than in Caucasian ones, and SLE patients carrying the GT20 allele are more likely to develop vascular arterial events (LUMINA multiethnic cohort). (iii) TRAF3IP2 may affect disease phenotype and, particularly, the occurrence of pericarditis. (iv) There is a considerable genetic component for CAD with IRF8 as a strong susceptibility locus.
(i) The presence of APS and its characteristic antibodies was the major independent contributor to the development of thrombotic events and severe organ damage. (ii) Polyautoimunity (e.g., APS) may suggest concerted pathogenic actions with other autoantibodies in the development of thrombotic events.
(i) SLE diagnosis is associated with carotid plaque formation and development of CV event. (ii) High percentage of patients with abnormal angiographic findings had higher ACR criteria number for SLE. (iii) Endothelial dysfunction is associated with traditional and SLE-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy.
(i) One of the independent predictors of vascular events in a multiethnic US cohort (LUMINA) was the presence of any APLA. (ii) Anti-2GPI antibodies were strongly associated with thrombosis. The decrease of anti-2GPI levels at the time of thrombosis may indicate a pathogenic role.
(iii) The higher frequency of aPT found in thrombosis may suggest concerted pathogenic actions with other autoantibodies in the development of thrombotic events. (iv) Patients with ACLA seem to be at an increased risk for arterial and venous thrombotic events and showed an association with echocardiographic abnormalities. (v) There was correlation between lupus anticoagulant and thrombotic events in Brazilian lupus patients.
Immune cells aberrations
(i) Complement fixing activity of ACLA seems to be relevant in thrombotic venous events. (ii) Activation of endothelial MMP-2 by MMP-9 contained in NETs as an important player in endothelial dysfunction and MMP-9 as a novel self-antigen in SLE. These results further support that aberrant NET formation plays pathogenic roles in SLE.
(i) HDL distribution and composition (−HDL2b, +HDL3b, and +HDL3c) were abnormal in SLE patients. (ii) Low HDL levels and increased TAG levels were associated with AT by cIMT measurement. (iii) SLE pattern of dyslipoproteinemia may increase the risk of developing CAD.
(i) Disease activity (SLAM) is an important determinant in the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events in the LUMINA cohort. (ii) SLEDAI scores were positively correlated with abnormal BMI and WC. (iii) Higher disease activity (i.e., SLEDAI and SLICC) is a predictor of CAC and it was independently associated with MetS, myocardial perfusion abnormalities, and thrombosis. Higher score of SDI was associated with atherosclerotic plaque in Brazilian SLE patients. (iv) SLE patients have a lipid profile abnormality which is aggravated by disease activity and may reside in a defect of VLDL metabolism. (v) There is a close link between MeTS and SLICC/ACR score with increased aortic stiffness.
(i) Baseline and accrued damage increase mortality risk (including due to CVD). (ii) Measured by SDI, patients had more peripheral vascular involvement. (iii) MetS was associated both with traditional risk factors for CHD and with lupus characteristics including damage index. (iv) There was a correlation between IMT and revised damage index (SLICC). (v) Atherosclerotic CV damage in SLE is multifactorial, and disease-related factors (including CRP levels and SDI at baseline) appear to be important contributors to such an occurrence.
(i) Longer duration of SLE was associated with atherosclerotic plaque and CV events. (ii) A correlation between IMT and duration of the disease was found in SLE patients. (iii) Disease duration was an independent predictor for premature CAC in young women with SLE.
(i) PDN >10 mg/day was independently associated with MetS and IMT in SLE patients. (ii) IHD was observed in SLE patients: those with long term steroid therapy and those with frank episodes of vasculitis.
(i) Current vasculitis was associated with abnormal myocardial scintigraphy. (ii) Patients with SLE and RP seem to be at increased risk for arterial and venous thrombotic events. IHD was observed in SLE patients: those with long term steroid therapy and those with frank episodes of vasculitis.
MetS were associated with traditional risk factors for CHD and lupus characteristics, including damage index and renal involvement (nephritic syndrome).
