Abstract P294: Greater Peripheral Vasoconstriction During Mental Stress Predicts Adverse Cardiovascular Outcomes

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Jeong Hwan Kim ◽  
Muhammad Hammadah ◽  
Ibhar Al Mheid ◽  
Kobina Wilmot ◽  
Ronnie Ramadan ◽  
...  

Introduction: Peripheral arterial vasoconstriction during mental stress (MS) has been associated with mental stress-induced myocardial ischemia, which in turn has been linked with worse cardiovascular outcomes. It is unknown whether the magnitude of peripheral vasoconstriction with MS is predictive of long term outcomes. Hypothesis: We hypothesized that greater peripheral arterial vasoconstriction during MS would be associated with adverse events among patients with coronary artery disease (CAD). Methods: Four hundred sixty-three patients with stable CAD and normal left ventricular function, (age 63±9, 75% male, 27% Black, EF 60±8 %) underwent MS testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured at baseline and during MS using peripheral arterial tonometry (PAT), and the PAT ratio of pulse wave amplitude (during mental stress/ baseline) was calculated. Cox proportional hazard models were calculated to examine the association between the PAT ratio and outcomes. Results: Median PAT ratio during MS was 0.68, indicating 32% average constriction with MS compared to rest. Subjects with greater peripheral constriction [low (<median) PAT ratio] were more likely to be male (80% vs. 70%, P=0.008) compared to those with PAT ratio ≥median, but their risk factor profiles were similar. During 2.8±0.5 year follow-up, 64 patients had adverse cardiac events including 7 cardiovascular deaths, 19 MI, and 54 revascularization events. After adjusting for age, sex, race, hypertension, diabetes, current smoking status, and prior MI, those with low PAT ratio had a greater risk of CV death/MI (HR[hazard ratio] 2.49, 95% CI [1.04-5.99]) and CV death/MI/revascularization (HR 1.77, 95% CI [1.03-3.04]) compared to those with high PAT ratio. Conclusion: Greater peripheral arterial vasoconstriction with MS is associated with a higher risk of adverse cardiovascular outcomes in patients with CAD.

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Zakaria Almuwaqqat ◽  
Chang Liu ◽  
Jeong Hwan Kim ◽  
Bruno B Lima ◽  
Muhammad Hammadah ◽  
...  

Background: Excessive peripheral microvascular constriction during acute psychological stress, measured using peripheral arterial tonometry reflects similar changes in coronary blood flow.The ratio of digital pulse wave amplitude during stress compared to rest (sPAT) is used to estimate the degree of microvascular response to stress. Hypothesis: We hypothesized that genetic factors contribute to the degree of microvascular constriction during mental stress and that excessive vasoconstriction is associated with adverse cardiovascular outcomes. Methods: A total of 580 stable CAD subjects of European and African ancestries from two prospective cohort studies underwent mental stress testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured using PAT and the stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated. Genotyping was performed using Illumina’s Multi-Ethnic Genotyping Array platform and imputed to the 1000 Genome reference panel. Ethnicity-specific genome-wide association studies (GWAS) of sPAT were conducted using linear regression of additive genetic mode adjusted for age, sex and population stratification in both cohorts. A trans-ethnic meta-analysis integrated the GWAS results from four sub-cohorts. Upon 5-year follow-up, Fine and Gray’s sub-distribution hazard ratios (sHR) were used to examine the association between sPAT ratio (> vs=< median) and the composite endpoint of cardiovascular death, myocardial infarction, revascularization, and hospitalization for heart failure. Results: Mean age was 63±9; 65% male, 35% African American. We identified three SNPs in linkage disequilibrium on chr7:111,666,943 T>C (rs6466396); chr7: 111,668,622 T>G (rs876170); chr7: 111,668,623 T>G (rs876169) that were associated with greater sPAT ratio by means of 0.13, 0.12 and 0.10, ( P = 1.42E-08). The sPAT-associated locus was within DOCK4 gene which encodes Dedicator of Cytokinesis 4, an essential protein for angiogenesis and brain development, and a known locus for obesity. After adjusting for demographic and cardiovascular risk factors, medications, and rate-pressure product change during mental stress, those with low sPAT ratio were at significantly higher risk of adverse outcomes (sHR 1.8 [95% CI 1.1 - 2.8]). Conclusion: We have identified a genetic basis for stress-induced vasomotion. Presence of allele C (rs6466396) is associated with increased vasoconstriction during mental stress, and thus may predispose CAD patients to a higher risk for adverse cardiovascular outcomes with stressful exposure.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Zakaria Almuwaqqat ◽  
Chang Liu ◽  
Jeong Hwan Kim ◽  
Qin Hui ◽  
Muhammad Hammadah ◽  
...  

Background: Excessive peripheral microvascular constriction during acute psychological stress, measured using peripheral arterial tonometry reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. The ratio of digital pulse wave amplitude during stress compared to rest (sPAT) is used to estimate the degree of microvascular response to stress. We sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. Methods: A total of 642 post-MI and stable CAD subjects from two prospective cohort studies underwent mental stress testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured using PAT and the stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated. Genotyping was performed using Illumina’s Multi-Ethnic Genotyping Array (MEGA) platform and imputed to the 1000 Genome reference panel. Race stratified genome-wide association studies (GWAS) of sPAT were conducted using linear regression of additive genetic mode adjusted for age, sex and population stratification in the two cohorts. A trans-ethnic meta-analysis integrated the four sets GWAS results. Results: Mean age was 63±9; 65% male, 35% Black. We identified two SNPs in linkage disequilibrium on chr4:185503564 and chr4:185491706 rs13353812 (with 35% and 28% allele frequency, respectively) that were associated with greater sPAT ratio ( P = 1.42E-08). The mean sPAT ratio during mental stress for subjects with none, one and two AT insertion alleles of SNP chr4:185503564 were 0.67, 0.76 and 0.93, respectively, an average of 12% (P < 0.001), per allele. Results were similar for G insertion alleles of SNP rs13353812. The nearest gene of the sPAT-associated locus is CASP3 which encodes caspase, an essential protein for apoptosis signaling and brain and hematopoietic stem cell development. Conclusion: We have identified a genetic basis for stress-induced vasomotion. Presence of the chr4:185503564 allele is associated with less vasoconstriction during mental stress, and thus may be protective against long term cardiovascular risk. These findings need further exploration.


2019 ◽  
Vol 125 (10) ◽  
pp. 874-883 ◽  
Author(s):  
Jeong Hwan Kim ◽  
Zakaria Almuwaqqat ◽  
Muhammad Hammadah ◽  
Chang Liu ◽  
Yi-An Ko ◽  
...  

Rationale: Excessive vasoconstriction in response to mental stress may be a potential mechanism by which acute psychological stress leads to adverse cardiac events. Objectives: We investigated whether excessive digital vasoconstriction during acute mental stress predicts adverse cardiovascular outcomes among patients with coronary artery disease. Methods and Results: Five hundred forty-nine patients with stable coronary artery disease (age 63±9, 76% male, 29% black) underwent mental stress testing with a standardized public speaking stressor and followed prospectively for cardiovascular end points. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated and dichotomized by the median value into low and high sPAT ratio groups. Upon 3-year follow-up, Fine and Gray’s subdistribution hazard ratios were used to examine the association between sPAT ratio and the composite end point of cardiovascular death, myocardial infarction, revascularization, and hospitalization for heart failure. The median sPAT ratio was 0.68 (interquartile range, 0.48–0.88), indicating 32% vasoconstriction with mental stress. Men were more likely to have low sPAT ratio than women (odds ratio, 1.79; P =0.007) while those on β-blockers were less likely to have low sPAT ratio (odds ratio, 0.52; P =0.003). After adjusting for demographic and cardiovascular risk factors, medications, and rate-pressure product change during mental stress, those with low sPAT ratio were at significantly higher risk of adverse outcomes (subdistribution hazard ratio, 1.77 [95% CI, 1.12–2.80]). Conclusions: Greater peripheral vasoconstriction with mental stress, denoted by a low sPAT ratio, is associated with a higher risk of adverse cardiovascular outcomes in patients with coronary artery disease.


2021 ◽  
Vol 5 (1) ◽  
pp. 99-109
Author(s):  
Kasra Moazzami ◽  
Matthew T. Wittbrodt ◽  
Bruno B. Lima ◽  
Jeong Hwan Kim ◽  
Zakaria Almuwaqqat ◽  
...  

Background: Individuals with coronary artery disease (CAD) have worse executive function compared to the general population but the mechanisms are unknown. Objective: To investigate the role of acute mental stress (MS) on the executive function of patients with CAD. Methods: Participants with stable CAD underwent acute MS testing with simultaneous peripheral vascular function measurements and brain imaging using high resolution-positron emission tomography. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during MS/baseline was calculated as a measure of microvascular constriction during MS. Plasma levels of catecholamine and interleukin-6 were assessed at baseline and after MS. Executive function was assessed both at baseline and at 2 years follow-up using the Trail Making Test parts A and B. Results: We studied 389 individuals with brain data available for 148 participants. Of this population follow-up cognitive assessments were performed in 226 individuals (121 with brain imaging). After multivariable adjustment for baseline demographics, risk factors, and medication use, a lower sPAT, indicating greater vasoconstriction, a higher inferior frontal lobe activation with MS, and increases in norepinephrine and IL-6 levels with MS were all independently associated with greater time to complete Trail B test.-38.4pt Conclusion: In response to acute MS, greater peripheral vasoconstriction, higher inferior frontal lobe brain activation, and increases in the levels of norepinephrine and IL-6 are associated with worse executive function.


SLEEP ◽  
2021 ◽  
Author(s):  
Bastien Lechat ◽  
Hannah Scott ◽  
Felix Decup ◽  
Kristy L Hansen ◽  
Gorica Micic ◽  
...  

Abstract Study Objectives This study was designed to test the utility of cardiovascular responses as markers of potentially different environmental noise disruption effects of wind farm compared to traffic noise exposure during sleep. Methods Twenty participants underwent polysomnography. In random order, and at six sound pressure levels from 33 dBA to 48 dBA in 3 dB increments, three types of wind farm and two types of road traffic noise recordings of 20-sec duration were played during established N2 or deeper sleep, each separated by 20 seconds without noise. Each noise sequence also included a no-noise control. Electrocardiogram and finger pulse oximeter recorded pulse wave amplitude changes from the pre-noise onset baseline following each noise exposure and were assessed algorithmically to quantify the magnitude of heart rate and finger vasoconstriction responses to noise exposure. Results Higher sound pressure levels were more likely to induce drops in pulse wave amplitude. Sound pressure levels as low as 39 dBA evoked a pulse wave amplitude response (Odds ratio [95% confidence interval]; 1.52 [1.15, 2.02]). Wind farm noise with amplitude modulation was less likely to evoke a pulse wave amplitude response than the other noise types, but warrants cautious interpretation given low numbers of replications within each noise type. Conclusion These preliminary data support that drops in pulse wave amplitude are a particularly sensitive marker of noise-induced cardiovascular responses during. Larger trials are clearly warranted to further assess relationships between recurrent cardiovascular activation responses to environmental noise and potential long-term health effects.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Nino Isakadze ◽  
Ayman Alkhoder ◽  
Arshed A Quyyumi ◽  
Viola Vaccarino ◽  
J. Douglas Bremner ◽  
...  

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. Hypothesis: We hypothesized that increased digital microvascular constriction during both mental stress and recovery are predictive of increased severity of mental stress ischemia. Methods: We evaluated 204 patients with stable CAD with high quality vascular data using a standardized mental stress test using a public speaking task. Peripheral artery tonometry (PAT) (Itamar Inc) was used to assess digital microvascular tone. Vasoconstriction was calculated as the ratio of pulse wave amplitude during speech/recovery and the last 3 minutes of baseline, with lower ratio indicating more vasoconstriction. 99mTc sestamibi myocardial perfusion imaging was performed at rest and with mental stress. A summed difference score (SDS) quantifying severity of reversible perfusion defects (inducible ischemia) comparing rest and stress images was computed using a standard 17-segment model. Four categories of increasing severity were based on cut points of 0, 3, and 6. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Each category of increase in ischemia severity was associated with a 10% (p=0.04) decrease in speech PAT ratio (Figure) and 11% (p=0.02) decrease in recovery PAT ratio. After multivariable adjustment for sociodemographics, traditional risk factors, medical history, medication use, and psychological risk factors, the associations persisted, with B=-11%, p=0.02 for speech PAT ratio, and B=-8%, p=0.04 for recovery ratio. Conclusion: Peripheral vasoconstriction during mental stress speech as well as recovery predicts MSI severity in a dose-response relationship.


2020 ◽  
Author(s):  
Dániel Kulin ◽  
Flóra Antali ◽  
Sándor Kulin ◽  
Dina Wafa ◽  
Konrád István Lucz ◽  
...  

Abstract Background Introduction of telemonitoring systems to patient care which provide extensive information about the cardiovascular status of the patient is a promising direction to reduce cardiovascular morbidity and mortality. Our team has developed a telemedical system which is based on the photoplethysmographic detection of the digital arterial pulse wave. The system incorporates a cloud-based automated algorithm which analyses the pulse contour to provide 15 scientifically established parameters for versatile characterization of cardiovascular function. The aim of the current study was to assess the variability of the measurements to test the applicability of the tool before clinical use. We assessed the repeatability of the measurements by detecting stable artificial signals, and also test-retest variability by repeatedly examining the pulse contours of healthy individuals under standardized conditions. Results Most contour parameters (stiffness index, reflection index, left ventricular ejection time index and mean interbeat intervals) are measured with high repeatability (coefficients of variation (CV) < 1% for each parameter), and exhibit acceptable intrapersonal fluctuations (CVs < 10%). However, some parameters derived from the second derivative of the pulse wave seem to be more variable (aging index, d/a ratio). This is explained by the typical alterations of the pulse wave under specific circumstances, which cause the flattening or complete disappearance of c and d inflections on the second derivative. Conclusion Our measurements proved that our telemonitoring system detects and analyses digital pulse contours with high accuracy and highlighted that second derivative parameters should be interpreted cautiously. We recommend the evaluation of these parameters only in those measurements where c and d points are detected reliably. Pulse contour parameters are stable in healthy individuals under standardized conditions, which allows detection of subtle abnormal alterations by the remote surveillance system.


SLEEP ◽  
2019 ◽  
Vol 42 (Supplement_1) ◽  
pp. A345-A345
Author(s):  
Camila Hirotsu ◽  
Pedro Marques-Vidal ◽  
Peter Vollenweider ◽  
Monica Betta ◽  
Giulio Bernardi ◽  
...  

2015 ◽  
Vol 37 (1) ◽  
pp. 52-66 ◽  
Author(s):  
Marit H N van Velzen ◽  
Arjo J Loeve ◽  
Minke C Kortekaas ◽  
Sjoerd P Niehof ◽  
Egbert G Mik ◽  
...  

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