Abstract 13760: Intensive versus Standard Blood Pressure Control in Patients With Peripheral Artery Disease: The Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Johanna Frary ◽  
Christina Byrne ◽  
Muthiah Vaduganathan ◽  
Tor Biering-srensen ◽  
Michael H Olsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Peripheral Artery Disease ◽  
Primary Outcome ◽  
Standard Group ◽  
Efficacy And Safety ◽  
Peripheral Artery ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Artery Disease

Background: High blood pressure (BP) is the strongest modifiable risk factor for cardiovascular (CV) disease and is highly prevalent among individuals with peripheral artery disease (PAD). Purpose: To assess the efficacy and safety of intensive versus standard BP control in patients with PAD, and to assess if the presence of PAD modified treatment effect. Methods: SPRINT was a randomized, controlled, open-label trial in which individuals aged ≥50 years, at high CV risk, and with a systolic BP 130-180 mmHg were randomized to intensive (systolic BP target <120mmHg) or standard BP control (systolic BP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, such as hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, or injurious falls. We assessed the risk of events in patients with PAD versus those without and assessed the efficacy and safety of intensive BP in patients with PAD. Subgroup heterogeneity was evaluated using interaction analyses. Results: Of 9361 participants, 503 (5.3%) had baseline PAD (intensive group 250 (5.3%) versus standard group 253 (5.4%); P=0.90). Median follow-up duration was 3.2 years (range 0-4.6 years). PAD was independently associated with a higher risk of both the primary outcome (hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.23-2.12; P<0.001) and composite serious adverse events (HR 1.49, 95% CI: 1.32-1.69; P<0.001). The presence of PAD did not modify the efficacy and safety of intensive versus standard BP control (P≥0.05). However, due to the higher baseline risk in PAD patients, the absolute risk reduction of the primary outcome with intensive treatment was larger compared with patients without PAD (1.8% versus 1.6%), as was the risk of death from any cause (2.3% versus 1.1%) (Figure) . Conclusion: Intensive BP control reduced CV events and death in patients with hypertension and PAD.

Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial

2021 ◽  
pp. 1358863X2198943
Author(s):  
Joshua T Slysz ◽  
W. Jack Rejeski ◽  
Diane Treat-Jacobson ◽  
Lydia A Bazzano ◽  
Daniel E Forman ◽  
...  
Keyword(s):  
Physical Activity ◽  
Clinical Trial ◽  
Adverse Events ◽  
Peripheral Artery Disease ◽  
Longitudinal Analyses ◽  
Peripheral Artery ◽  
Serious Adverse Events ◽  
Cross Sectional ◽  
Sf 36 ◽  
Artery Disease

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle–brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustained PA with 6-minute walk (6MW) distance and the Short Form-36 physical functioning domain (SF-36 PF) score in cross-sectional analyses and with serious adverse events (SAEs) in longitudinal analyses of people with PAD. PA was measured continuously for 10 days using a tri-axial accelerometer at baseline in 277 participants with PAD randomized to the LITE clinical trial. In regression analyses, each 0.15 lower ABI value was associated with a 5.67% decrease in the number of daily bouts of sustained PA (95% CI: 3.85–6.54; p < 0.001). Every additional bout of sustained PA per day was associated with a 4.56-meter greater 6MW distance (95% CI: 2.67–6.46; p < 0.0001), and a 0.81-point improvement in SF-36 PF score (95% CI: 0.34–1.28; p < 0.001). Participants with values of daily bouts of sustained PA below the median had higher rates of SAEs during follow-up, compared to participants above the median (41% vs 24%; p = 0.002). In conclusion, among participants with PAD, lower ABI values were associated with fewer bouts of daily sustained PA. A greater number of bouts of daily sustained PA were associated with better 6MW performance and SF-36 PF score, and, in longitudinal analyses, lower rates of SAEs. Clinicaltrials.gov ID: NCT02538900.

Abstract 14373: Efficacy and Safety of Antihypertensive Drug Classes: The Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christina Byrne ◽  
Anubodh Varshney ◽  
Zaid Almarzooq ◽  
Kristian H Kragholm ◽  
Maria L Krogager ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Antihypertensive Drug ◽  
Primary Outcome ◽  
Control Group ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Drug Classes ◽  
Safety Outcomes

Purpose: To assess the efficacy and safety of antihypertensive drug classes, including angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), beta blockers (BB), calcium channel blockers (CCB), and thiazide diuretics (TD), in subjects at high cardiovascular (CV) risk. Methods: SPRINT was a randomized, controlled, open-label trial in which individuals without diabetes aged ≥50 years, at high CV risk, and with a systolic blood pressure (SBP) 130-180 mmHg were randomized to intensive (SBP target <120mmHg) or standard BP control (SBP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, i.e., hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, and falls. Associations between baseline antihypertensive drug classes, efficacy, and safety outcomes, stratified by level of SBP control, were examined using Cox proportional-hazards regression. Results: Of 9361 participants, baseline use of antihypertensive agents was as follows: ACEi/ARB in 1317 (14%), BB in 911 (10%), CCB in 796 (9%), and TD in 979 (10%). A total of 1366 (15%) subjects did not have a record of being on an antihypertensive drug at baseline. In the intensive BP control group, use of a BB-based regimen at baseline was associated with a significantly higher risk of the primary outcome when compared with no medications ( Figure ). Similar patterns were observed for secondary efficacy endpoints. The risk of serious adverse events tended to be lower in patients receiving a treatment regimen containing either an ACEi/ARB or a TD compared with those receiving a regimen containing a BB or a CCB ( Figure ). Conclusions: In SPRINT, the risk of adverse events was lowest in patients who were not on an antihypertensive drug at baseline. ACEi/ARB-based and TD-based regimens appeared to have the best balance between efficacy and safety.

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

2018 ◽  
Vol 314 (2) ◽  
pp. H246-H254 ◽  
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.

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.

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

2020 ◽  
Vol 318 (4) ◽  
pp. H916-H924 ◽  
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.

Vascular Inflammation, Calf Muscle Oxygen Saturation, and Blood Glucose are Associated With Exercise Pressor Response in Symptomatic Peripheral Artery Disease

Angiology ◽  
2019 ◽  
Vol 70 (8) ◽  
pp. 747-755 ◽  
Author(s):  
Andrew W. Gardner ◽  
Polly S. Montgomery ◽  
Ming Wang ◽  
Chixiang Chen ◽  
Marcos Kuroki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Oxygen Saturation ◽  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Calf Muscle ◽  
Peripheral Artery ◽  
Muscle Oxygen ◽  
Artery Disease ◽  
Vascular Biomarkers

We determined whether calf muscle oxygen saturation (StO2) and vascular biomarkers of inflammation and oxidative stress were associated with an exercise pressor response during treadmill walking in 179 patients with symptomatic peripheral artery disease (PAD). The exercise pressor response was measured as the change in blood pressure from rest to the end of the first 2-minute treadmill stage (2 mph, 0% grade). There was a wide range in the change in systolic blood pressure (−46 to 50 mm Hg) and in diastolic blood pressure (−23 to 38 mm Hg), with mean increases of 4.3 and 1.4 mm Hg, respectively. In multiple regression analyses, significant predictors of systolic pressure included glucose ( P < .001) and insulin ( P = .039). Significant predictors of diastolic pressure included cultured endothelial cell apoptosis ( P = .019), the percentage drop in exercise calf muscle (StO2; P = .023), high-sensitivity C-reactive protein ( P = .032), and glucose ( P = .033). Higher levels in pro-inflammatory vascular biomarkers, impaired calf muscle StO2 during exercise, and elevated blood glucose were independently associated with greater exercise pressor response in patients with symptomatic PAD. The clinical implication is that exercise and nutritional interventions designed to improve inflammation, microcirculation, and glucose metabolism may also lower blood pressure during exercise in patients with symptomatic PAD.

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