Inter-Arm Blood Pressure Difference in Diabetes Mellitus and Its Preferential Association with Peripheral Artery Disease

Background: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. Methods: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient’s characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan–Meier curves. Results: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus ( p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). Conclusion: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.

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Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00498.2017 ◽

2018 ◽

Vol 314 (2) ◽

pp. H246-H254 ◽

Cited By ~ 6

Author(s):

Evan A. Kempf ◽

Korynne S. Rollins ◽

Tyler D. Hopkins ◽

Alec L. Butenas ◽

Joseph M. Santin ◽

...

Keyword(s):

Blood Pressure ◽

Peripheral Artery Disease ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Peripheral Artery ◽

Nerve Activity ◽

Exercise Pressor Reflex ◽

Pressor Reflex ◽

Artery Disease ◽

Dynamic Stretch

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.

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

10.1101/2020.08.23.20180240 ◽

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.

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Management of Patients with Diabetes Mellitus and Peripheral Artery Disease in the General Practice

Journal of General Practice ◽

10.4172/2329-9126.1000e107 ◽

2015 ◽

Vol 03 (03) ◽

Author(s):

George Galyfos

Keyword(s):

Diabetes Mellitus ◽

General Practice ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Patients With Diabetes ◽

Artery Disease

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Performance of a clinical/proteomic panel to predict obstructive peripheral artery disease in patients with and without diabetes mellitus

Open Heart ◽

10.1136/openhrt-2018-000955 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000955 ◽

Cited By ~ 3

Author(s):

Cian P McCarthy ◽

Shreya Shrestha ◽

Nasrien Ibrahim ◽

Roland R J van Kimmenade ◽

Hanna K Gaggin ◽

...

Keyword(s):

Diabetes Mellitus ◽

Peripheral Artery Disease ◽

Predictive Value ◽

Characteristic Curve ◽

Kidney Injury ◽

Clinical Variable ◽

Peripheral Artery ◽

Peripheral Vessel ◽

Artery Disease ◽

Kidney Injury Molecule 1

BackgroundPatients with diabetes mellitus (DM) are at substantial risk of developing peripheral artery disease (PAD). We recently developed a clinical/proteomic panel to predict obstructive PAD. In this study, we compare the accuracy of this panel for the diagnosis of PAD in patients with and without DM.Methods and resultsThe HART PAD panel consists of one clinical variable (history of hypertension) and concentrations of six biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1 and eotaxin-1). In a prospective cohort of 354 patients undergoing peripheral and/or coronary angiography, performance of this diagnostic panel to detect ≥50% stenosis in at least one peripheral vessel was assessed in patients with (n=94) and without DM (n=260). The model had an area under the receiver operating characteristic curve (AUC) of 0.85 for obstructive PAD. At optimal cut-off, the model had 84% sensitivity, 75% specificity, positive predictive value (PPV) of 84% and negative predictive value (NPV) of 75% for detection of PAD among patients with DM, similar as in those without DM. In those with DM, partitioning the model into five levels resulted in a PPV of 95% and NPV of 100% in the highest and lowest levels, respectively. Abnormal scores were associated with a shorter time to revascularisation during 4.3 years of follow-up.ConclusionA clinical/biomarker model can predict with high accuracy the presence of PAD among patients with DM.Trial registration numberNCT00842868.

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Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00493.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. H916-H924 ◽

Cited By ~ 1

Author(s):

Danielle Jin-Kwang Kim ◽

Marcos Kuroki ◽

Jian Cui ◽

Zhaohui Gao ◽

J. Carter Luck ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Peripheral Artery Disease ◽

Plantar Flexion ◽

Peripheral Artery ◽

Exercise Pressor Reflex ◽

Femoral Blood Flow ◽

Femoral Blood ◽

Pressor Reflex ◽

Artery Disease

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([Formula: see text]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [Formula: see text] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

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