P-selectin and sST2 as prognostic biomarkers of cardiovascular events in patients with multiple myeloma following anticancer therapy and severe COVID-19

Atrial fibrillation is an independent predictor of cardiovascular events in patients with primary aldosteronism

Background Anti-cancer drugs used to treat multiple myeloma (MM) can cause several cardiovascular toxic effects. HFA/ICOS risk score stratification is used to assess the baseline cardiovascular risk of cancer patients and its effectiveness has been demonstrated in breast cancer patients and some hematological malignancies but not in MM. In addition, patients with MM can have AL cardiac amyloidosis that can worsen the prognosis. Purpose to assess the effectiveness of HFA-ICOS risk score in predicting cardiovascular events in MM patients and the influence of cardiac amyloidosis and AL score on prognosis. Methods A prospective study was carried out enrolling 71 patients with MM (35 women and 36 men; mean age 68±10 years) treated with proteasome inhibitors with or without immunomodulators and daratumumab. Cardiological evaluation was performed before starting anti-cancer drugs and after a median period of 1 years. HFA/ICOS risk score and AL score were assessed in all patients at baseline. Cardiovascular events were assessed: cardiovascular death, heart failure hospitalization, arrhythmias, myocardial ischaemia, venous thromboembolism, new onset of arterial hypertension, cancer therapy-related cardiac dysfunction. Patients were divided into 2 groups: patients with HFA/ICOS risk core high and very high (A), patients with low and medium HFA/ICOS risk score (B). Results Group A included 26 patients, group B included 45 patients; 19 patients had AL cardiac amyloidosis and were included in group A. Cardiovascular adverse events were significantly higher in group A (65,38%) than group B (24,4%). In particular, cardiovascular death, hospitalization for heart failure and atrial fibrillation were significantly higher in group A, especially in patients with cardiac amyloidosis. Using logistic regression analysis, cardiovascular events were significantly associated with HFA/ICOS risk score high and very high, AL score ≥ 5, cardiac amyloidosis, heart failure, global longitudinal strain (GLS) and NT-pro BNP value at baseline, left ventricular mass at echocardiogram and left atrial volume indexed (p value < 0,05). At multiple regression analysis, only HFA/ICOS risk score, GLS and NT-pro BNP were independent predictors of cardiovascular events. A GLS value -10.5% and a NT-pro BNP value >164.50 mg/dl have been identified as the parameters capable of predicting events with the greatest sensitivity and specificity (AUC 1, p value < 0,0001). All patients with cardiac amyloidosis had CV events. Conclusion Our study confirms the effectiveness of HFA/ICOS risk score in patients with MM and the need to identify the presence of cardiac amyloidosis in these patients using AL score. Also AL score is associated with CV events and it is able to identify cardiac amyloidosis. NT-proBNP and GLS (included respectively in HFA/ICOS score and AL score) are independent predictors of CV events in MM patients and it should be assessed before starting treatment.

Circulating levels of the TGF β-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with unstable coronary artery disease (CAD). To explore the prognostic utility of GDF-15 in patients with stable CAD, we analyzed the relation of GDF-15 to mortality and cardiovascular (CV) events in the AtheroGene registry which enrolled consecutive patients with stable angina and at least one stenosis >30% in a larger coronary artery. Patients were followed for a median of 3.6 years. Serum samples for measurement of GDF-15 along with other biomarkers were available from 1352 patients. Two pre-specified cutoff points (1200 and 1800 ng/L) were used to identify different risk groups. 55.9%, 26.4%, and 17.7% of the patients presented with GDF-15 values <1200 ng/L, between 1200 and 1800 ng/L, and >1800 ng/L, respectively. Increasing levels of GDF-15 were related to age (P<0.001), hypertension (P=0.01), diabetes mellitus (P<0.001), low HDL cholesterol (P<0.001), and the extent of CAD (P=0.001). Moreover, significant relations to hsCRP, troponin T, NT-proBNP, and reduced renal function (GFR) were observed (all P<0.001). Increasing levels of GDF-15 were associated with an increased risk of all-cause mortality (P<0.001, log-rank test), CV mortality (P<0.001), and CV events (P<0.001). Receiver operating curve analyses confirmed GDF-15 as a strong marker of 2-year adverse outcomes (area under the curve for all-cause mortality, 0.79; CV mortality, 0.81; CV events, 0.70). By multiple Cox regression analysis, GDF-15 emerged as an independent predictor of all-cause mortality (HR 2.1 per one standard deviation of lnGDF-15 [95% CI 1.6 –2.8], P<0.001), CV mortality (HR 2.2 [95% CI 1.5–3.3], P<0.001), and CV events (HR 1.7 [95% CI 1.3–2.4], P=0.001) after adjustment for baseline characteristics, clinical variables, LDL/HDL ratio, hsCRP, troponin T, NT-proBNP, and GFR. Patients with a GDF-15 level above 1800 ng/L had a highly elevated risk of CV mortality even in the fully adjusted model (HR 5.2 [95% CI 1.6 –16.1], P=0.005). These data identify GDF-15 as a powerful and independent biomarker of mortality and CV events in patients with stable CAD.

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Background: Cardiovascular events are one of the most serious complications that increase the risk of mortality and morbidity in pre-dialysis and on-dialysis chronic kidney disease (CKD) patients. Activation of the renin–angiotensin–aldosterone system (RAAS) is considered to contribute to the development of cardiovascular events in these populations. Therefore, several kinds of RAAS blockers have been frequently prescribed to prevent cardiovascular events in patients with CKD; however, their effectiveness remains controversial. This systematic review focuses on whether RAAS blockers prevent cardiovascular events in patients with CKD. Method: PubMed were searched to retrieve reference lists of eligible trials and related reviews. Randomized prospective controlled trials that investigated the effects on cardiovascular events in CKD patients that were published in English from 2010 to 2020 were included. Results: Among 167 identified studies, 11 eligible studies (n = 8,322 subjects) were included in the meta-analysis. The meta-analysis showed that RAAS blockers significantly reduced cardiovascular events in on-dialysis patients with CKD [three studies; odds ratio (OR), 0.52; 95% confidence interval (CI), 0.36 to 0.74; p = 0.0003], but there was no significant difference in pre-dialysis patients with CKD because of the heterogeneity in each study (eight studies). We also investigated the effects of each kind of RAAS blocker on cardiovascular events in CKD patients. Among the RAAS blockers, mineralocorticoid receptor antagonists significantly decreased cardiovascular events in pre-dialysis or on-dialysis patients with CKD (four studies; OR, 0.60; 95%CI, 0.50 to 0.73, p < 0.0001). However, angiotensin receptor blockers did not show significant effects (four studies; OR, 0.65; 95%CI, 0.42 to 1.01; p = 0.0529). The effects of angiotensin converting enzyme inhibitors and direct renin inhibitors on cardiovascular events in patients with CKD could not be analyzed because there were too few studies. Conclusion: Mineralocorticoid receptor antagonists may decrease cardiovascular events in pre-dialysis or on-dialysis patients with CKD.

Why P Is Not Perfect

Aims:The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD).Methods:We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words “methotrexate,” “cardiovascular,” “acute coronary syndrome,” “coronary heart disease,” “myocardial infarction,” “angina pectoris,” and “rheumatoid arthritis.” The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death.Results:A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726–0.876, P = .001, I2 = 27. 9%).Conclusion:MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.

Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. However, their power to predict cardiovascular events in patients with peripheral artery disease (PAD) is unknown and is addressed in the present study. We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0)/Cer(18:1/24:0) and Cer(18:1/24:1)/Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (Figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31-2.35], p&amp;lt;0.001). We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients. Disclosure A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. I. Baumgartner: None. H. Drexel: None. J.F. Dopheide: None.

Serum ceramides and type 2 diabetes are mutually independent predictors of cardiovascular events in patients with peripheral artery disease

Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥ 10 mmHg for predicting CV events in patients with chronic kidney disease (CKD). The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events. We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m(2), and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV events. Increased IASBPD is an independent predictor of CV events in CKD patients.

COUNTERPOINT: Should Asymptomatic OSA Be Treated in Patients With Significant Cardiovascular Disease? No

P4497Serum ceramides and type 2 diabetes are mutually independent predictors of cardiovascular events in patients with peripheral artery disease

P11-09 Ankle-brachial index measured by an automated oscillometric method as a predictor of cardiovascular events in patients with coronary artery disease

Since our retrospective study has formed a mathematical formula, α = f(x1, …, x252), where α is the probability of cardiovascular events in patients with heart failure (HF) and x1 is each clinical parameter, we prospectively tested the predictive capability and feasibility of the mathematical formula of cardiovascular events in HF patients. First of all, to create such a mathematical formula using limited number of the parameters to predict the cardiovascular events in HF patients, we retrospectively determined f(x) that formulates the relationship between the most influential 50 clinical parameters (x) among 252 parameters using 167 patients hospitalized due to acute HF; the nonlinear optimization could provide the formula of α = f(x1, …, x50) which fitted the probability of the actual cardiovascular events per day. Secondly, we prospectively examined the predictability of f(x) in other 213 patients using 50 clinical parameters in 3 hospitals, and we found that the Kaplan–Meier curves using actual and estimated occurrence probabilities of cardiovascular events were closely correlated. We conclude that we created a mathematical formula f(x) that precisely predicted the occurrence probability of future cardiovascular outcomes of HF patients per day. Mathematical modelling may predict the occurrence probability of cardiovascular events in HF patients.

Aim. To identify factors associated with long-term adverse cardiovascular events (CVEs) in patients with type 2 diabetes (T2D).Material and methods. The study included 94 T2D patients aged 40 to 65 years with or without early symptoms of heart failure (HF). Patients underwent clinical and laboratory investigations, 6-minute walk test (6MWT), and echocardiography. Concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined. After 8,8±0,72 years of follow-up, the prevalence of following CVEs among patients were assessed: any-cause death, myocardial infarction, stroke, emergency myocardial revascularization, hospitalization due to decompensated HF. We assessed the relationship between the development of long-term CVEs in T2D patients and the initial characteristics using logistic regression model.Results. Over a period of 8,8±0,72 years, CVEs occurred in 34 out of 88 (38,6%) patients with T2D. The baseline 6MWT values were lower in patients with CVEs (391,8±56,2 m vs 418,8±53,9 m, p=0,04). Stable coronary artery disease (55,9% vs 27,8%, p=0,008), early-stage HF (61,8% vs 27,8%; p=0,0016) were more common among patients with CVEs. Patients with CVEs had higher median initial NT-proBNP (46,9 pg/ml vs 24,2 pg/ml, p=0,01) and mean left atrial (LA) size (4,5±0,6 cm vs 4,19±0,5 cm, p=0,04) levels. The logistic regression established following factors associated with long-term CVEs in patients with T2D: NT-proBNP level (p=0,05), LA size (p=0,01), and 6MWT results (p=0,002).Conclusion. The development of long-term CVEs in middle-aged T2D patients with or without early-stage HF is associated with an initially increased NT-proBNP levels, an increase in left atrial size, and a decrease in 6MWT values. Further prospective studies with larger samples are needed to identify other factors affecting outcome in patients with early signs of HF.