High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy.

BACKGROUND: Cancer therapy-related cardiovascular toxicity (CTR-CVT) from immune checkpoint inhibitor (ICI) therapy is still incompletely characterized, and patients with pre-existing cardiovascular disease represent a particularly high-risk cohort. Valid parameters for risk stratification of these patients are missing. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict mortality and adverse events in other cardiovascular cohorts. The present study aims to examine the predictive capacity of NLR for risk stratification of patients particularly vulnerable for CTR-CVT under ICI therapy. METHODS: We performed an analysis of 88 cancer patients (69 ± 11 years, 25% female) with pre-existing cardiovascular disease under ICI therapy from the prospective Essen Cardio-Oncology Registry (ECoR). NLR was assessed at patient enrollment and the population was divided through receiver operator characteristic (ROC) curve analysis in patients with low (< 4.57) and high (≥ 4.57) NLR. Endpoint was the whole spectrum of CTR-CVT, according to the European guidelines on cardio-oncology. The median follow-up was 357 days (interquartile range (IQR): 150-509 days). RESULTS: We observed 4 cases of myocarditis, 17 cases of vascular toxicity, 3 cases of arterial hypertension, 22 cases of arrhythmia or QTc prolongation and 17 cases of cardiovascular dysfunction. NLR was associated with overall CTR-CVT by univariable Cox regression (hazard ratio (HR): 1.443; 95% confidence interval (CI) 1.082-1.925; p = 0.013). However, this association was attenuated after adjusting for further confounders. CONCLUSION: NLR is moderately associated with CTR-CVT in cancer patients with pre-existing cardiovascular disease under ICI therapy. Surveillance of NLR during ICI therapy might be an effective and economically biomarker for risk stratification in these high-risk patients.

Right ventricular and atrial strain in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy.

AIMS: While immune checkpoint inhibitor (ICI) therapy significantly improves survival rates in advanced melanoma, ICI can evoke severe immune-related cardiovascular adverse events. Right ventricular (RV) dysfunction negatively impacts the outcomes in cardiovascular diseases and may be an early sign for overall cardiotoxicity. We aimed to assess RV function in melanoma patients undergoing ICI therapy using conventional echocardiographic and strain imaging techniques. METHODS AND RESULTS: We retrospectively examined 30 patients (40% women, age 59 ± 13 years) with advanced melanoma (stage III/IV) before and 4 weeks after the start of ICI therapy (follow-up at 39 ± 15 days); n = 15 of the patients received nivolumab, and n = 15 received the combination therapy nivolumab/ipilimumab. Two-dimensional echocardiography with assessment of RV longitudinal strain of the free wall (RV-LSFW) and assessment of right atrial (RA) strain from speckle tracking was performed at baseline and after the start of ICI therapy. Short-term ICI therapy caused a reduction of RV-LSFW (-25.5 ± 6.4% vs. -22.4 ± 4.3%, P = 0.002) and of RA strain during contraction phase (-10.6 ± 3.5% vs. -7.7 ± 3.1%, P = 0.001). Conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and pulmonary artery systolic pressure were not different between the two time points (TAPSE 26 ± 5 vs. 25 ± 5 mm, P = 0.125; FAC 38 ± 13% vs. 38 ± 14%, P = 0.750; and pulmonary artery systolic pressure 27 ± 10 vs. 25 ± 8 mmHg, P = 0.268). CONCLUSIONS: Analysis of RV and RA strain shows alterations even in a short-term follow-up, while changes in RV function are not visible by conventional RV parameters. Alterations in RV and RA strain could be early signs of cardiotoxicity and therefore should be assessed in patients undergoing ICI therapy.

Left Ventricular Diastolic Function Following Anthracycline-Based Chemotherapy in Patients with Breast Cancer without Previous Cardiac Disease-A Meta-Analysis.

BACKGROUND: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. METHODS: Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e') and E/e' ratio) echocardiographic parameters. RESULTS: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e' and E/e' ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. CONCLUSIONS: ANT had a modest early impact on E/A ratio, without changing EDT, e', or E/e' in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.

Assessment of coronary artery disease during hospitalization for cancer treatment.

BACKGROUND: With improvement of cancer-specific survival, comorbidities and treatment-related side effects, particularly cardiovascular toxicities, need close attention. The aim of the present study was to evaluate clinical characteristics and outcomes of cancer patients requiring coronary angiography during inpatient care. METHODS: We performed a retrospective analysis of patients hospitalized between 02/2011 and 02/2018 in our two university hospital cancer centers. From a cohort of 60,676 cancer patients, we identified 153 patients (65.7 ± 11.6 years, 73.2% male), who underwent coronary angiography and were eligible for analysis. These were compared to a control group of 153 non-cancer patients pair-matched with respect to age, sex, and indication for catheterization. RESULTS: Cancer patients presented in 66% with an acute coronary syndrome (ACS). The most prevalent cancer entities were lymphoma (19%) and lung cancer (18.3%). The rate of primary percutaneous coronary interventions (PCI) was significantly lower in the cancer cohort (40.5% vs. 53.6%, p = 0.029), although manifestation of coronary artery disease (CAD) and PCI results were comparable (SYNergy between PCI with TAXus and cardiac surgery (SYNTAX)-score, delta pre- and post-PCI - 9.8 vs. - 8.0, p = 0.2). Mortality was remarkably high in cancer patients (1-year mortality 46% vs. 8% in non-cancer patients, p < 0.001), particularly with troponin-positive ACS (5-year mortality 71%). CONCLUSION: Strategies to effectively control cardiovascular risks in cancer patients are needed. Additionally, suspected CAD in cancer patients should not prevent prompt diagnostic clarification and optimal revascularization as PCI results in cancer patients are comparable to non-cancer patients and occurrence of troponin-positive ACS leads to a significantly increased risk of mortality.

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AIMS: Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. METHODS AND RESULTS: PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). CONCLUSIONS: BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement: A Single-Center Study.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. OBJECTIVES: The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. METHODS: Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. RESULTS: A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. CONCLUSIONS: TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis.

AIMS: Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction. METHODS AND RESULTS: Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). ß-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466). CONCLUSION: Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis.

Importance: Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. Objective: To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy. Data Sources: PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018. Study Selection: Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Data Extraction and Synthesis: Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs. Main Outcomes and Measures: The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded. Results: Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02). Conclusions and Relevance: Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.

Heart failure from cancer therapy: can we prevent it?

AIMS: Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta-analysis aims to assess the efficacy of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity. METHODS AND RESULTS: We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta-blockers or ACE inhibitors/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline-based chemotherapy have a moderate yet significant benefit in LVEF from beta-blockers or ACEs/ARBs. The beta-blocker analysis included 769 cancer patients, and the ACE inhibitors/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta-blocker group and the control group was 2.57% (95% confidence interval 0.63-4.51, P = 0.009). The mean difference for ACE inhibitors/ARBs was 4.71% (95% confidence interval 0.38-9.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies. CONCLUSIONS: Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid-lowering approaches are required to improve protection for cardio-oncology patients.

Comparison of pulse wave velocity assessed by three different techniques: Arteriograph, Complior, and Echo-tracking.

Arterial stiffness estimated by pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. Although recommended by the current guidelines, clinical applicability of this parameter is difficult, due to differences between the various techniques used to measure it and to biological variability. Our aim was to compare PWV assessed by 3 different commercially available systems. 100 subjects (51 ± 16 years, 45 men) were evaluated using the 3 methods: an oscillometric technique (Arteriograph, PWV-A); a piezo-electric method (Complior, PWV-C); and an high-resolution ultrasound technique implemented with an Echo-tracking system (Aloka, PWV-E). Conventional biological markers were measured. Correlations of PWV measured by the 3 methods were poor (r = 0.39, r = 0.39, and r = 0.31 for PWV-A vs. PWV-C, PWV-A vs. PWV-E, and PWV-C vs. PWV-E, respectively, all p < 0.05). By Bland-Altman analysis, mean difference (±SD) of PWV-A vs. PWV-C was -1.9 ± 2.0 m/s, of PWV-A vs. PWV-E -3.6 ± 1.9 m/s, and of PWV-C vs. PWV-E -2.7 ± 1.9 m/s, with a wide coefficient of variation (22.3, 25.7, and 25.7 %, respectively). As expected, PWV-A, PWV-C, and PWV-E correlated with other arterial stiffness parameters, such as intima-media thickness (r = 0.22, r = 0.22, and r = 0.36, respectively), E p (r = 0.37, r = 0.26, and r = 0.94, respectively), and augmentation index measured by Arteriograph method (r = 0.66, r = 0.35, and r = 0.26, respectively); all p < 0.05. Assessment of PWV is markedly dependent on the technique used to measure it, related to various methods for measuring traveled distance of the arterial wave. Our results suggest the urgent need to establish reference values of PWV for each of these techniques, separately, to be used in routine clinical practice.

The Assessment of Subclinical Cardiovascular Dysfunction in Treated Rheumatoid Arthritis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) causes frequently cardiovascular complications, probably determined by early atherosclerosis in connection to chronic systemic inflammation. Purpose of our study was to assess subclinical cardiac and vascular dysfunction, and to evaluate the mechanisms of ventriculo-arterial interaction, in patients with correctly treated RA vs. normal subjects. METHODS: We evaluated 46 subjects (55±10 years, 2 men): 29 patients with seropositive treated RA (mean duration of 11±9 years), without documented cardiovascular or pulmonary disease, and 17 control subjects, matched for age, sex, and distribution of conventional major risk factors. All RA patients were under long-term treatment (more than 6 months) with Methotrexat + Sulfasalasine (22 patients) or Methotrexat + Sulfasalasine + Infliximab (7 patients). We determined biomarkers of inflammation (P-selectin, interleukines 1, 6, 10, 18, seric amiloid A, á-TNF, ã-interferon, C-reactive protein, anti-oxidated LDL antibodies), myocardial fibrosis (â-crosslaps) and ventricular overload (BNP). We assessed the parameters of cardiac function by standard and tissue Doppler echocardiography, intima-media thickness and arterial stiffness by "e-tracking" and "wave intensity analysis" (at the level of the right carotid artery), endothelial function by flow mediated dilation (FMD), and carotid-femoral pulse wave velocity by the Complior method. RESULTS: Biological parameters of inflammation, markers of myocardial fibrosis and of ventricular overload were not different between the 2 study groups. Also, parameters of subclinical cardiac and vascular function were similar between the two groups. RA patients had subclinical RV dysfunction, correlated to the duration of the disease. They also tended to have higher values of systolic pulmonary artery pressure than normals. CONCLUSION: Correctly treated patients with RA, with controlled systemic inflammation, have normal LV, endothelial and arterial function. However, in the absence of documented pulmonary disease, they do have subclinical RV dysfunction, correlated with the duration of disease. This suggests an intrinsic RV myocardial involvement but, since pulmonary artery pressure was also higher, a secondary mechanism might be also involved.

Growth hormone deficiency in adults impacts left ventricular mechanics: a two-dimensional speckle-tracking study.

BACKGROUND: Growth hormone deficiency (GHD) in adults is associated with increased cardiovascular events, but detailed assessment of cardiac and vascular function is lacking. Thus we assessed cardiac, arterial, and endothelial functions, using conventional and speckle-tracking echocardiography, in adults with GHD compared with controls with similar cardiovascular risk. METHODS: Fifty-two patients with GHD (47 ± 16 years; 34 men) and no cardiovascular disease or diabetes were enrolled prospectively and compared with 50 age- and sex-matched controls. Comprehensive echocardiography was performed in all participants. Regional left ventricular (LV) function was assessed from global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), whereas LV torsion (LVtor) was calculated from basal (RotB) and apical (RotA) rotations. Arterial function was assessed from intima-media thickening, local wave speed, and beta index of stiffness, whereas endothelial function was assessed from flow-mediated dilation. Levels of pro-brain natriuretic peptide (proBNP) were measured. RESULTS: GLS and GCS were decreased more in patients with GHD than in controls (-17.2% ± 2.7% vs. -19.3% ± 3.3% and -15.9% ± 5.4% vs. -18.8% ± 3.5%; both P < 0.01), whereas GRS was similar. RotB and LVtor were also decreased in patients with GHD (-4.8° ± 2.6° vs. -6.2° ± 2.1°/cm and 1.8° ± 0.6° vs. 2.3° ± 1.1°/cm; both P < 0.05). ProBNP was increased in patients with GHD (61.0 ± 74 pg/dL vs. 24.7 ± 21 pg/dL; P = 0.002). Arterial and endothelial functions were similar between groups. CONCLUSIONS: In conclusion, adults with GHD had LV longitudinal dysfunction and increased proBNP levels compared with controls, suggesting intrinsic myocardial disease. Further studies are needed to assess if this cardiac impairment in adults with GHD is reversible after GH replacement.

The efficiency of continuous positive airway pressure therapy in reducing cardiovascular dysfunction in a patient with arterial hypertension and obstructive sleep apnea.

Obstructive sleep apnea (OSA) has been included by European and American hypertension therapy guidelines as a common cause of high blood pressure. Recent studies have demonstrated a strong link between OSA and HBP and the treatment thereof should consist of combination therapy, especially in patients with refractory AHT and a non-dipping profile. We present the case of a patient with high grade hypertension, with secondary organ damage and severe OSA. The ultimate method for controlling blood pressure and reversing subclinical cardiac and cerebrovascular dysfunction of this patient was the specific therapy with continuous positive airway pressure (cPAP).

Atherosclerosis in Systemic Sclerosis: a Modern Controversy.

Systemic sclerosis (SSc) is a chronic disease of unknown etiology. The main feature of SSc is microvascular disease, but contemporary studies in the field have confirmed the presence of macrovascular affectation. Due to its inflammatory background, and higher cardio- and cerebrovascular death rates, it is presumed that SSc is more frequently associated to accelerated atherosclerosis, similarly to other autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis. The assessment of subclinical atherosclerosis in patients with SSc through different methods (such as intima media thickness, echo-tracking, wave intensity, pulse wave velocity, flow mediated dilation, nitroglycerin mediated dilation, ankle brachial pressure index or coronary angiotomography) has failed to show concordant results, regardless of the used tool. In this review, we try to synthetise the most recent evidence about atherosclerotic involvement in SSc, reviewing the association between SSc and risk factors and also performing a summary of studies that compared atherosclerosis in SSc to controls. Our research leads to the conclusion that in order to elucidate the extent of atherosclerosis and its consequences in SSc, further investigations are needed, combining atherosclerosis assessment tools and larger number of patients.