Abstract P141: A Novel GWAS Locus Influences Microvascular Response to Acute Psychological Stress

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.

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Abstract MP10: A Novel Genetic Locus Influences Microvascular Reactivity To Acute Psychological Stress

Circulation ◽

10.1161/circ.143.suppl_1.mp10 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Zakaria Almuwaqqat ◽

Chang Liu ◽

Jeong Hwan Kim ◽

Bruno B Lima ◽

Muhammad Hammadah ◽

...

Keyword(s):

Psychological Stress ◽

Mental Stress ◽

Wave Amplitude ◽

Pulse Wave ◽

Association Studies ◽

Cardiovascular Outcomes ◽

Genome Wide Association Studies ◽

Pulse Wave Amplitude ◽

Digital Pulse ◽

Acute Psychological Stress

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.

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

Circulation ◽

10.1161/circ.137.suppl_1.p294 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Jeong Hwan Kim ◽

Muhammad Hammadah ◽

Ibhar Al Mheid ◽

Kobina Wilmot ◽

Ronnie Ramadan ◽

...

Keyword(s):

Mental Stress ◽

Wave Amplitude ◽

Pulse Wave ◽

Smoking Status ◽

Left Ventricular ◽

Cardiovascular Outcomes ◽

Peripheral Vasoconstriction ◽

Pulse Wave Amplitude ◽

Digital Pulse ◽

Peripheral Arterial

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.

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Neurobiological Pathways Linking Acute Mental Stress to Impairments in Executive Function in Individuals with Coronary Artery Disease

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-200287 ◽

2021 ◽

Vol 5 (1) ◽

pp. 99-109

Author(s):

Kasra Moazzami ◽

Matthew T. Wittbrodt ◽

Bruno B. Lima ◽

Jeong Hwan Kim ◽

Zakaria Almuwaqqat ◽

...

Keyword(s):

Coronary Artery Disease ◽

Executive Function ◽

Coronary Artery ◽

Frontal Lobe ◽

Mental Stress ◽

Wave Amplitude ◽

Pulse Wave ◽

Pulse Wave Amplitude ◽

Artery Disease

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.

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Peripheral Vasoconstriction During Mental Stress and Adverse Cardiovascular Outcomes in Patients With Coronary Artery Disease

Circulation Research ◽

10.1161/circresaha.119.315005 ◽

2019 ◽

Vol 125 (10) ◽

pp. 874-883 ◽

Cited By ~ 3

Author(s):

Jeong Hwan Kim ◽

Zakaria Almuwaqqat ◽

Muhammad Hammadah ◽

Chang Liu ◽

Yi-An Ko ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Odds Ratio ◽

Mental Stress ◽

Wave Amplitude ◽

Pulse Wave ◽

Cardiovascular Outcomes ◽

Subdistribution Hazard ◽

Pulse Wave Amplitude ◽

Artery Disease

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.

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Plethysmographic pulse wave amplitude and future leg arteriosclerosis

Atherosclerosis ◽

10.1016/0021-9150(94)05427-k ◽

1995 ◽

Vol 113 (1) ◽

pp. 55-62 ◽

Cited By ~ 6

Author(s):

M Ögren

Keyword(s):

Wave Amplitude ◽

Pulse Wave ◽

Pulse Wave Amplitude

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Environmental noise-induced cardiovascular responses during sleep

SLEEP ◽

10.1093/sleep/zsab302 ◽

2021 ◽

Author(s):

Bastien Lechat ◽

Hannah Scott ◽

Felix Decup ◽

Kristy L Hansen ◽

Gorica Micic ◽

...

Keyword(s):

Wind Farm ◽

Wave Amplitude ◽

Sound Pressure ◽

Noise Exposure ◽

Pulse Wave ◽

Traffic Noise ◽

Cardiovascular Responses ◽

Environmental Noise ◽

Pulse Wave Amplitude ◽

Sound Pressure Levels

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.

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0860 Pulse Wave Amplitude Drops During Sleep: Reference Values And Clinical Associations In A General Population

SLEEP ◽

10.1093/sleep/zsz067.858 ◽

2019 ◽

Vol 42 (Supplement_1) ◽

pp. A345-A345

Author(s):

Camila Hirotsu ◽

Pedro Marques-Vidal ◽

Peter Vollenweider ◽

Monica Betta ◽

Giulio Bernardi ◽

...

Keyword(s):

General Population ◽

Reference Values ◽

Wave Amplitude ◽

Pulse Wave ◽

Pulse Wave Amplitude ◽

Clinical Associations

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Effect of heat-induced pain stimuli on pulse transit time and pulse wave amplitude in healthy volunteers

Physiological Measurement ◽

10.1088/0967-3334/37/1/52 ◽

2015 ◽

Vol 37 (1) ◽

pp. 52-66 ◽

Cited By ~ 4

Author(s):

Marit H N van Velzen ◽

Arjo J Loeve ◽

Minke C Kortekaas ◽

Sjoerd P Niehof ◽

Egbert G Mik ◽

...

Keyword(s):

Healthy Volunteers ◽

Transit Time ◽

Wave Amplitude ◽

Pulse Wave ◽

Pulse Transit Time ◽

Pulse Wave Amplitude ◽

Pain Stimuli

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Reactions to Cold Exposure Emphasize the Need for Weather Protection in Prehospital Care: An Experimental Study

Prehospital and Disaster Medicine ◽

10.1017/s1049023x00003940 ◽

2006 ◽

Vol 21 (5) ◽

pp. 316-320 ◽

Cited By ~ 7

Author(s):

Niina S. Lintu ◽

M. Health ◽

Matti A.K. Mattila ◽

Jaana A. Holopainen ◽

Mari Koivunen ◽

...

Keyword(s):

Tympanic Membrane ◽

Cold Exposure ◽

Room Temperature ◽

Wave Amplitude ◽

Pulse Wave ◽

Prehospital Care ◽

Emg Activity ◽

Pulse Wave Amplitude ◽

Vital Functions ◽

Skin Temperatures

AbstractIntroduction:Exposure to cold temperature is a serious but often neglected problem in prehospital care. It not only is an uncomfortable, subjective experience, but it also can cause severe disturbances in vital functions, gradually leading to hypothermia.Objective:The aim of this study was to examine healthy subjects'physiological and subjective reactions to cold exposure (30 minutes at -5°C in the a climatic chamber) while they were lying in a protective covering.Methods:Healthy volunteers (n = 20) participated in the experiment, which consisted of a 10-minute stabilization period of vital functions at room temperature (23°C), 30 minutes of cold exposure (-5°C), and a 30-minute recovery period at room temperature. Subjects lay supinely in protective covering during the entire experiment. Skin temperatures, oxygen saturation, pulse rates, pulse wave amplitude in the middle finger, and surface electromyography (EMG) activity of the major pectoral muscle were recorded continuously during the test. Before and immediately after the cold exposure, tympanic membrane temperatures were measured. In addition, subjects were asked to estimate cold using a standard scale.Results:During the cold exposure, the decrease in tympanic membrane temperature was not significant.The pulse wave amplitude in the finger decreased sharply upon entering the cold chamber. Skin temperatures, especially of the fingers and toes, decreased during the cold exposure.There were no clear signs of shivering in electromyographic recordings. Subjective cold feelings followed decreasing skin temperatures. Skin temperatures did not return quickly. Even 30 minutes after the exposure, all the skin temperatures still had not returnedto normal levels.However, subjective cold feeling was relieved immediately.Conclusions:Cold exposure provoked immediate protective vasoconstriction in the peripheral compartment, which caused linear decreases of local skin temperatures. This probably was triggered from the unprotected face and upper respiratory areas.

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