Calcification Propensity in Serum and Cardiovascular Outcome in Peripheral Artery Disease

Author(s):  
Marija Bojic ◽  
Bernhard Bielesz ◽  
Daniel Cejka ◽  
Gerit-Holger Schernthaner ◽  
Clemens Höbaus

AbstractPeripheral artery disease (PAD) has been shown to be linked to elevated cardiovascular risk. The novel T50 test quantifies calcification propensity of serum and has been associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD) and in the general population. This study investigated the association of calcification propensity measured by the T50 test in 287 patients with PAD without severe CKD. Major cardiovascular events (MACEs) including nonfatal stroke and nonfatal myocardial infarction and all-cause death (MACE + ) were evaluated after a median follow-up of 4 years and long-term cardiovascular and all-cause mortality after a median follow-up of 8.7 years by Kaplan–Meier and Cox regression analyses. Mean T50 time was 268 ± 63 minutes in the study cohort (age 69 ± 10 years, 32% women, 47% diabetes). Low T50 values that signify high calcification propensity were significantly associated with the occurrence of MACE+ (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.55–0.94). This association sustained multivariate adjustment for cardiovascular risk factors (CVRFs), Fontaine PAD stage, and prevalent media sclerosis (HR: 0.65; CI: 0.47–0.91). Cardiovascular mortality was significantly associated with T50 after multivariate adjustment for CVRF (HR: 0.72; CI 0.53–0.99), but not all-cause mortality (HR: 0.80; CI: 0.64–1.01). In conclusion, calcification propensity associates with MACE+ and cardiovascular mortality in patients with PAD.

Author(s):  
Jörn F Dopheide ◽  
Jonas Veit ◽  
Hana Ramadani ◽  
Luise Adam ◽  
Lucija Papac ◽  
...  

Abstract Aims  We hypothesized that adherence to statin therapy determines survival in patients with peripheral artery disease (PAD). Methods and results  Single-centre longitudinal observational study with 691 symptomatic PAD patients. Mortality was evaluated over a mean follow-up of 50 ± 26 months. We related statin adherence and low-density lipoprotein cholesterol (LDL-C) target attainment to all-cause mortality. Initially, 73% of our PAD patients were on statins. At follow-up, we observed an increase to 81% (P < 0.0001). Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/day (P < 0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/dL (P < 0.0001). The proportion of patients receiving a high-intensity statin increased over time from 38% to 62% (P < 0.0001). Patients never receiving statins had a significant higher mortality rate (31%) than patients continuously on statins (13%) or having newly received a statin (8%; P < 0.0001). Moreover, patients on intensified statin medication had a low mortality of 9%. Those who terminated statin medication or reduced statin dosage had a higher mortality (34% and 20%, respectively; P < 0.0001). Multivariate analysis showed that adherence to or an increase of the statin dosage (both P = 0.001), as well as a newly prescribed statin therapy (P = 0.004) independently predicted reduced mortality. Conclusion  Our data suggest that adherence to statin therapy is associated with reduced mortality in symptomatic PAD patients. A strategy of intensive and sustained statin therapy is recommended.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C H Saely ◽  
A Vonbank ◽  
B Larcher ◽  
A Mader ◽  
M Maechler ◽  
...  

Abstract   The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. The purpose of this study was to investigate how the incidence of major cardiovascular events compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes (T2DM). We prospectively recorded major cardiovascular events and death over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123). When compared to the incidence of MACE in CAD+/T2DM- patients (25.1%), it was significantly higher in CAD+/T2DM+ patients (35.4%; p<0.001), in PAD+/T2DM- patients (30.2%; p=0.022) and in PAD+/T2DM+ patients (47.2%; p<0.001). Patients with both PAD and T2DM in turn were at a higher risk than CAD+/T2DM+ or PAD+/T2DM- patients (p=0.001 and p<0.001, respectively). The incidence of MACE did not differ significantly between PAD+/T2DM- and CAD+/T2DM+ patients (p=0.413). Compared to patients with CAD, Cox regression analyses after multivariate adjustment showed an adjusted hazard ratio of 1.46 [1.14–1.87], p=0.002 for the presence of PAD. Conversely, T2DM increased the risk of MACE after multivariate adjustment in CAD and PAD patients (adjusted HR 1.58 [1.27–1.98], p<0.001). In conclusion, our data show that T2DM and the presence of PAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of MACE. FUNDunding Acknowledgement Type of funding sources: None.


2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72).Conclusions: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  

Abstract Background Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients. Objective To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). Research design and methods We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up. Results Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72). Conclusions This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.


2019 ◽  
Vol 28 (5) ◽  
pp. 410-417 ◽  
Author(s):  
Ibrahim Al-Zakwani ◽  
Ekram Al Siyabi ◽  
Najib Alrawahi ◽  
Arif Al-Mulla ◽  
Abdullah Alnaeemi ◽  
...  

Objective: To evaluate the association between peripheral artery disease (PAD) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. Methods: Data from 4,044 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 were analyzed. PAD was defined as any of the following: claudication, amputation for arterial vascular insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention in the extremities, documented aortic aneurysm or an ankle brachial index of <0.8 in any of the legs. MACE included stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons diagnosed between hospital admission and at 1-year post discharge. Analyses were performed using univariate and multivariate statistical techniques. Results: The overall mean age of the cohort was 60 ± 13 years and 66% (n = 2,686) were males. A total of 3.3% (n = 132) of the patients had PAD. Patients with PAD were more likely to be associated with smoking, prior MI, hypertension, diabetes mellitus, and stroke/TIA. At the 1-year follow-up, patients with PAD were significantly more likely to have MACE (adjusted OR [aOR], 2.07; 95% confidence interval [CI]: 1.41–3.06; p< 0.001). The higher rates of events were also observed across all MACE components; stroke/TIA (aOR, 3.22; 95% CI: 1.80–5.75; p< 0.001), MI (aOR, 2.15; 95% CI: 1.29–3.59; p =0.003), all-cause mortality (aOR, 2.21; 95% CI: 1.33–3.69; p =0.002), and readmissions for cardiac reasons (aOR, 1.83; 95% CI: 1.24–2.70; p =0.003). Conclusions: PAD was significantly associated with MACE in ACS patients in the Arabian Gulf.


2021 ◽  
Vol 9 (2) ◽  
pp. e002407
Author(s):  
Lukas Sprenger ◽  
Arthur Mader ◽  
Barbara Larcher ◽  
Maximilian Mächler ◽  
Alexander Vonbank ◽  
...  

IntroductionThe prevalence of type 2 diabetes mellitus (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes is unclear and is addressed in the present study.Research design and methodsWe prospectively recorded major cardiovascular events (MACE; ie, cardiovascular death, myocardial infarction or stroke) over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM−; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM−; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123).ResultsThe event rate for MACE increased over our four investigated groups: it was lowest in CAD/T2DM− patients (2.52 events per 100 person-years). It was significantly higher in CAD/T2DM+ patients (3.96 events per 100 person-years; p<0.001), in PAD/T2DM− patients (3.68 events per 100 person-years; p=0.022), and in PAD/T2DM+ patients (7.10 events per 100 person-years; p<0.001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM− patients (p=0.001 and p<0.001, respectively). Cox regression analysis after multivariate adjustment showed that the presence of T2DM (HR=1.44 (95% CI 1.09 to 1.92); p=0.012) and the presence of PAD versus CAD (HR=1.48 (95% CI 1.15 to 1.91); p=0.002) were mutually independent predictors of cardiovascular events.ConclusionsIn conclusion, our data show that T2DM as well as the presence of PAD versus CAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of cardiovascular events.


2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline level of Sortilin levels, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin serum levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, Sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between Sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using Sortilin levels the prediction of MACE incidence improved [area under the curve (AUC) = 0.94] and MALE (AUC = 0.72).Conclusions: This study demonstrates that Sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hooman Bakhshi ◽  
PRAMITA BAGCHI ◽  
Zahra Meyghani ◽  
Behnam N Tehrani ◽  
Parveen K Garg ◽  
...  

Introduction: Coronary artery calcium score (CACs) measured by non-contrast cardiac CT has a strong correlation with coronary atherosclerotic burden. Although CACs predicts incident coronary heart disease, its gender-specific association with incident peripheral artery disease (PAD) is not clear. Methods: The multi-ethnic study of atherosclerosis (MESA) is a prospective population-based cohort consisting of 6814 men and female free of overt cardiovascular disease at enrollment. In this study we included MESA participants with baseline CACs and at least one ankle brachial index (ABI) measured at follow up exams. We excluded participants with baseline ABI≤ 0.9 or> 1.4. Incident PAD was defined as a follow up ABI≤ 0.9 and decline of ≥15%. Multivariable logistic regression models were deployed to evaluate the association between baseline CACs and incident PAD in female and male. Results: The mean age (SD) was 61.29 (9.96) years and 52.6% (3013/5725) were female. Female had lower baseline ABI [1.10 (0.08) vs 1.15 (0.09); p < 0.001]. Over a median (IQR) of 9.23 (8.22-9.60) years, 113(4%) female and 85(3%) male developed PAD. Every one unit increase in log (CACs+1) was associated with 1.11-fold higher odds of incident PAD in male (p=0.001). This association remained significant after adjustment for demographics, traditional cardiovascular risk factor and baseline ABI. Male participants with CACs>300 showed 1.94-fold higher odds of incident PAD compared to participant with CACs=0 (p=0.005). In female there was no statistically significant association between CACs and incident PAD in multivariable analysis. Conclusions: Baseline CACs is associated with future PAD independent of traditional cardiovascular risk factors in male participants of a multi-ethnic cohort. Disclaimer statement: The views expressed in this abstract are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.


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