scholarly journals Association of Hypertension and Arterial Blood Pressure on Limb and Cardiovascular Outcomes in Symptomatic Peripheral Artery Disease

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Marat Fudim ◽  
Charles W. Hopley ◽  
Zhen Huang ◽  
Sarah Kavanagh ◽  
Frank W. Rockhold ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Hazard Ratio ◽  
Peripheral Artery ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertension and office systolic blood pressure (SBP) with major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). Methods and Results: The EUCLID trial (Examining the Use of Ticagrelor in Peripheral Artery Disease) included 13 885 participants with symptomatic peripheral artery disease; median follow-up was 30 months. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for any MACE, MALE, and MALE including lower extremity revascularization. A clinical history of arterial hypertension was present in 10 857 (78%) participants, and these participants were older and more likely to be female when compared with the 3026 (22%) patients without hypertension. In patients with a history of hypertension, the adjusted hazard ratio for MACE was 0.94, 95% CI, 0.82–1.08; P =0.39, and the adjusted hazard ratio for MALE was 1.08, 95% CI, 0.96–1.23; P =0.21. During follow-up, average SBP was 135 mm Hg (125–145). Every 10 mmHg increase in SBP>125 mmHg was associated with an increased risk of MACE (HR, 1.10 [95% CI, 1.06–1.14]; P <0.001), a marginally increased risk of MALE (HR, 1.07 [95% CI, 1.00–1.15]; P =0.062), and an increased risk of MALE/lower extremity revascularization (HR, 1.08 [95% CI, 1.04–1.11]; P <0.001). Every decrease in 10 mmHg SBP ≤125 mmHg was associated with an increased risk of MACE (HR, 1.19 [95% CI, 1.09–1.31]; P <0.001) but not MALE or MALE/lower extremity revascularization (HR, 1.02 [95% CI, 0.84–1.23], P =0.824; HR, 1.04 [95% CI, 0.95–1.13], P =0.392, respectively). Conclusions: History of hypertension was not associated with higher hazard for MACE or MALE in patients with peripheral artery disease. In contrast, there was a higher hazard of MACE in patients with out-of-target low and high SBP. High but not low SBP was associated with an increased risk of ischemic limb events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

scholarly journals Ankle-Brachial Index for Risk Stratification in Patients With Symptomatic Peripheral Artery Disease With and Without Prior Lower Extremity Revascularization: Observations From the EUCLID Trial

2021 ◽  
Author(s):  
William R. Hiatt ◽  
Connie N. Hess ◽  
Marc P. Bonaca ◽  
Sarah Kavanagh ◽  
Manesh R. Patel ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Cubic Spline ◽  
Hazard Ratio ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: A reduced ankle-brachial index (ABI) is a measure of atherosclerosis and is associated with ischemic risk in the general population. Whether this relationship is maintained in peripheral artery disease after lower extremity revascularization (LER), which can modify ABI, is unknown. Methods: The EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) enrolled 13 885 patients with symptomatic peripheral artery disease; 57% with prior LER, and 43% with ABI ≤0.80. The primary major adverse cardiovascular events (MACE) outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Major adverse limb events (MALE) included acute limb ischemia and major amputation. An adjusted Cox proportional hazards model demonstrated a nonlinear relationship between ABI and outcomes. A restricted cubic spline model with 4 knots was developed to identify the best fitting model to describe the relationship between ABI and MACE and MALE risk. Results: Baseline ABI (mean±SD) was 0.77±0.21 in participants with prior LER and 0.63±0.14 in those without prior LER ( P <0.0001). There was no statistical interaction between prior LER and ABI, meaning the shapes of the cubic spline models were similar between groups. In those with prior LER, for every 0.10 unit lower ABI below an ABI of 1.00, the hazard ratio for MACE was 1.08 (95% CI, 1.04–1.12; P <0.0001), below an ABI of 0.80 the hazard ratio for MALE was 1.32 (95% CI, 1.21–1.43; P <0.0001). In patients without prior LER, every 0.10 unit lower ABI below an ABI of 0.70 was associated with increased risk for MACE (hazard ratio, 1.14 [95% CI, 1.06–1.23]; P =0.0004) and MALE (hazard ratio, 1.27 [95% CI, 1.08–1.49]; P =0.003). Conclusions: Patients with established peripheral artery disease, particularly those with prior LER, have an increased risk of MACE and MALE. The ABI remains a strong predictor of MACE and MALE ischemic events with an inverse relationship below an ABI threshold for patients with and without prior LER. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

P935Effect of hypertension and systolic blood pressure on cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: the EUCLID trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Hiatt ◽  
C W Hopley ◽  
S Kavanagh ◽  
M R Patel ◽  
I Baumgartner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Peripheral Artery Disease ◽  
Limb Ischemia ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Cardiac Events ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease

Abstract Background Hypertension is a risk factor for major adverse cardiac events (MACE) in patients with symptomatic peripheral artery disease (PAD). Purpose The effects of a history of hypertension and baseline systolic blood pressure (SBP) on MACE and major adverse limb events (MALE), including acute limb ischemia and major amputation, were evaluated in the Examining Use of tiCagreLor In paD (EUCLID) trial. Methods EUCLID randomized 13,885 patients with PAD and found no benefit of ticagrelor compared with clopidogrel on risk of MACE or MALE. The median duration of follow up was approximately 30 months. This post hoc, subgroup analysis evaluated the effects of hypertension history at baseline on the hazard for MACE and MALE. An adjusted restricted cubic spline regression analysis evaluated the association of SBP with MACE and MALE. Results A clinical history of hypertension was present in 10,857 (78%) patients at baseline and these patients were more likely to be older, female, white or African American, and reside in North America compared with the 3026 without hypertension. Hypertension was associated with a higher prevalence of concomitant cardiovascular diseases, polyvascular disease, diabetes, and prior coronary interventions. MACE occurred at a rate of 4.63 events/100 pt-yrs in participants with hypertension and 3.64 events/100 pt-yrs in participants without hypertension, (adjusted hazard ratio [aHR] 0.94, 95% CI 0.82–1.08; p=0.38). MALE occurred at a rate of 1.11 events/100 pt-yrs in those with hypertension and 1.38 events/100 pt-yrs in those without hypertension (p=0.054) (aHR 0.93 (95% CI 0.73, 1.18) p=0.55. The adjusted spline model for MACE and SBP demonstrated a significantly non-linear relationship with a HR 1.08 (95% CI 1.01, 1.15), p=0.0275 for every 10-unit decrease <135 mmHg SBP and HR 1.11 (1.06, 1.16), p<0.0001 for every 10-unit increase >135 mmHg (figure). There was no association between baseline SBP and MALE events. Conclusions A history of hypertension was not associated with a higher adjusted hazard for MACE or MALE in participants with PAD. In contrast, SBP at baseline was associated with increased risk of MACE at values both above and below 135 mmHg. Acknowledgement/Funding EUCLID was sponsored by AstraZeneca

scholarly journals Association of Health Status Scores With Cardiovascular and Limb Outcomes in Patients With Symptomatic Peripheral Artery Disease: Insights From the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) Trial

2020 ◽  
Vol 9 (19) ◽  
Author(s):  
Jennifer A. Rymer ◽  
Hillary Mulder ◽  
Kim G. Smolderen ◽  
William R. Hiatt ◽  
Michael S. Conte ◽  
...  
Keyword(s):  
Health Status ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Peripheral Artery ◽  
Vas Scores ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5‐Dimensions [EQ‐5D], EQ visual analog scale [VAS], and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization procedures during trial follow‐up and the association between 12‐month health status change scores and subsequent end points during follow‐up. There were 13 217 (95%) patients with EQ‐5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ‐5D tertile (0 to <0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79–1.0; P <0.01). Patients in the lowest VAS (0–60) and peripheral artery questionnaire (0–49) tertiles had lower ankle–brachial indices compared with the highest tertiles (80–100 and 76–108, respectively; P <0.01). There was a significant association between baseline EQ‐5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization ( P <0.05). Improved EQ‐5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower‐extremity revascularization (all P <0.01). Conclusions Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.

scholarly journals Genetic Variation in Blood Pressure and Lifetime Risk of Peripheral Artery Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Michael G Levin ◽  
Derek Klarin ◽  
Venexia M Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Peripheral Artery Disease ◽  
Genetic Correlations ◽  
Channel Blockers ◽  
Peripheral Artery ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Genes Encoding ◽  
Artery Disease

Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Million Veteran Program; N = 24,009 cases, 150,983 controls), and coronary artery disease (CAD; CARDIoGRAMplusC4D 1000 Genomes; N = 60,801 cases, 123,504 controls). Genetic correlations between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and CAD and PAD were estimated using LD score regression. The strongest correlation was between SBP and CAD (rg = 0.36; p = 3.9 x 10-18). Causal effects were estimated by two-sample MR using a range of pleiotropy-robust methods. Increased SBP, DBP, and PP increased risk of both PAD (SBP OR 1.25 [1.19-1.31] per 10mmHg increase, p = 3 x 10-18; DBP OR 1.27 [1.17-1.39], p = 4 x 10-8; PP OR 1.51 [1.38-1.64], p = 1 x 10-20) and CAD (SBP OR 1.37 [1.29-1.45], p = 2 x 10-24; DBP OR 1.6 [1.45-1.76], p = 7 x 10-22; PP OR 1.56 [1.4-1.75], p = 1 x 10-15). The effects of SBP and DBP were greater for CAD than PAD (pdiff = 0.024 for SBP, pdiff = 4.9 x 10-4 for DBP). Increased liability to PAD increased PP (beta = 1.04 [0.62-1.45] mmHg per 1 unit increase in log-odds in liability to PAD, p = 1 x 10-6). MR was also used to estimate the effect of BP lowering through different classes of antihypertensive medications using genetic instruments containing BP-trait associated variants located within genes encoding protein targets of each medication. SBP lowering via calcium channel blocker-associated variants was protective of CAD (OR 0.38 per 10mmHg decrease in SBP; 95% CI 0.19-0.77; p = 0.007). Conclusions: Higher BP is likely to cause both PAD and CAD but may have a larger effect on CAD risk. BP-lowering through calcium-channel blockers (as proxied by genetic variants) decreased risk of CAD.

Effect of vorapaxar on cardiovascular and limb outcomes in patients with peripheral artery disease with and without coronary artery disease: Analysis from the TRA 2°P-TIMI 50 trial

2020 ◽  
Vol 25 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Arman Qamar ◽  
David A Morrow ◽  
Mark A Creager ◽  
Benjamin M Scirica ◽  
Jeffrey W Olin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Absolute Risk ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (–2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474

scholarly journals Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study

2017 ◽  
Vol 23 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Adelaide M Arruda-Olson ◽  
Homam Moussa Pacha ◽  
Naveed Afzal ◽  
Sara Abram ◽  
Bradley R Lewis ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Inception Cohort ◽  
Peripheral Artery ◽  
Community Based ◽  
Increased Risk ◽  
Artery Disease ◽  
Recurrent Hospitalization ◽  
Over Time

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Baseline Serum ◽  
Increased Risk ◽  
Artery Disease

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.

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