Table 2.
Summary of All Published Cross-Sectional Studies Evaluating the Relationship Between Experimentally Induced Mental Stress and Peripheral Vascular Reactivitya
| Reference | Year | Sample size N (no. of males) |
Population | Experimental stressor | Measure of peripheral vascular reactivity | Other measures | Principle finding | Other finding(s) |
|---|---|---|---|---|---|---|---|---|
| 79 | 1999 | 40 (21) | Healthy adults aged 25–44 y | Reaction time/shock avoidance, mirror trace, and anger interview | Brachial artery endothelial function measured by ultrasonography in response to RH (FMD) | BP and SVR | A high EDAD was associated with lower resting systolic and diastolic BP | SVR responses during MS testing were greater for individuals with lower EDAD responses |
| EDAD was not associated to BP response to MS | ||||||||
| 78 | 2000 | 18 (18) | 10 healthy males; 8 non–insulin-dependent diabetic males | Structured speech task | Brachial artery endothelial function measured by ultrasonography in response to RH (FMD) | Endothelial-independent function following infusion of nitroglycerin | In healthy subjects, FMD (5.0±2.1%) was significantly (P<.01) reduced at 30 and 90 min after MS (2.8±2.3% and 2.3±2.4%, respectively) and returned toward normal after 4 h (4.1±2.0%) | Diabetic subjects had lower FMD than controls (3.0±1.5% vs 5.0±2.1%, respectively; P=.02) but showed no changes in FMD (2.7±1.1% after 30 min, 2.8±1.9% after 90 min, and 3.1±2.3% after 240 min) or GTN responses after MS |
| MS had no effect on the response to GTN | ||||||||
| In studies without MS, FMD did not change | ||||||||
| 80 | 2002 | 23 | Healthy subjects without CV risk factors | Colored light response | Brachial artery endothelial function measured by ultrasonography in response to RH (FMD) | FMD before and after MS during intra-arterial infusion of a selective endothelin A receptor antagonist (BQ-123) | Endothelium-dependent vasodilation was reduced by half for about 45 min (8.0±1.1% vs 4.1±1.0%; P<.002), whereas endothelium-independent vasodilation to nitroglycerin | Intra-arterial infusion of the selective endothelin-A receptor antagonist, but not saline prevented the impairment of endothelium-dependent vasodilation (8.6±1.2 versus 9.4±1.3%; NS) |
| Endothelial-independent function following infusion of nitroglycerin | remained unaffected (15.6±1.6 vs 14.3±1.3%; NS) | Intra-arterial infusion of norepinephrine of similar duration as MS did not inhibit FMD | ||||||
| 81 | 2004 | 16 (16) | Previously diagnosed CAD with positive exercise tress tests | Mental arithmetic stress test with harassment | PAT measurements during MS compared to baseline | ERNA | In 8 patients both ERNA and PAT were abnormal | When considering an abnormal PAT tracing as indicative of MSIMI, concordance of the 2 methods was 88% |
| Considered abnormal when PAT decreased by ≥20% from baseline | Myocardial ischemia diagnosed when global EF fell ≥8% during MS or new/worsened focal wall motion abnormalities | In 6 patients both tests were negative | ||||||
| In 2 cases results were discordant | ||||||||
| 82 | 2006 | 16 (0) | Postmenopausal women with angina and normal coronary angiogram | Anger recall task (an incident that made patients angry and that involved interpersonal interactions) | Brachial artery endothelial function measured by ultrasonography in response to RH (FMD) | Technetium 99m methoxyisobutylisonitrile myocardial scintigraphy at rest, MS and exercise | During MS testing, 6 patients (group I) had reversible perfusion defects on myocardial scintigraphy; other 10 patients (group II) did not | No group I patients had ischemia on Holter monitoring; 2 of 10 group II patients had ischemia |
| 24-h ambulatory ECG recording (Holter monitor) | Group I patients exhibited PED more frequently than those in group II (83% vs 20%) | |||||||
| Myocardial scintigraphy showed anteroapical/septal ischemia in 5 patients and inferoapical ischemia in 1 other patient, with both types of stress | ||||||||
| In group II patients, none showed a reversible perfusion defect during physical or MS | ||||||||
| 83 | 2008 | 211 (134) | Patients with established stable CAD | Public speaking task | PAT measurements during MS compared with baseline | BP and heart rate were recorded during rest and MS | Stress PAT ratio was significantly higher in women (0.80±0.72) compared with men (0.59±0.48), P=.032 | MS induced significant changes in systolic BP, diastolic BP, heart rate, and double product compared with rest in all subjects, P<.001 |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Remained significant after controlling for confounders, P=.037 | Comparing hemodynamic responses with MS across sexes did not show differences in systolic BP, diastolic BP, heart rate, or double product | ||||||
| 84 | 2008 | 87 (34) | Healthy subjects | Three different MS tasks of 6-min duration in random order (number-letter recall challenge of increasing length and complexity; number subtraction; Stroop word-color conflict) | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | In response to MS, male subjects had an increase in RH-PAT compared with baseline RH-PAT compared with females, who showed a decline in PEF (13.7% vs −0.47%; P=.01) | Double product (systolic BP × heart rate) | Males had a greater double product response to MS (27.2+3.6% increase in double product vs 19.2+1.7%; P=.01) |
| PAT measurements during MS compared with baseline | Stress PAT ratio tended to be greater in males than females (0.79±0.07 vs 0.9±0.04, respectively; P=.07) | |||||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Females who showed the least vasoreactivity to MS showed the greatest decline in PEF (−10.5+4% vs 17.4 + 6.3%; P<.001) | |||||||
| 85 | 2009 | 68 (60) | Patients with established stable CAD | Anger recall periods | PAT measurements during MS compared with baseline | Single PET-CT MPI concurrent with PAT testing during MS protocol | 26 developed a new perfusion defect during MS | Sensitivity/specificity of PAT ratio as an index of ischemia on PET-CT MPI was 0.62/0.63 |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Patients with a new perfusion defect with MS had a lower stress PAT ratio (0.76±0.04 vs 0.91±0.05, P= .03) | Among patients taking ACE-I the sensitivity and specificity increased to 0.86 and 0.73, respectively | ||||||
| 90% of patients without ischemia were correctly identified | ||||||||
| 86 | 2009 | 211 (134) | Patients with established stable CAD | Two phases of a public speaking task (stress anticipation and task performance) | PAT measurements during MS compared with baseline | Rest-stress MPI | Vascular response in the anticipation period (speech preparation) was more pronounced than during the actual speaking task | Stress PAT ratio during speech preparation had modest accuracy for predicting MSIMI on MPI(AUC, 0.63; 95% CI, 0.53-0.74; P=.015) |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Mean preparation stress PAT ratio 0.64±0.53; mean speech stress PAT ratio 0.72±0.60; P<.001) | |||||||
| 74 | 2010 | 26 (0) | 12 females with a history of ABS; 12 post-menopausal controls; 4 with history of MI | Three different MS tasks of 6-min duration in random order (number-letter recall challenge of increasing length and complexity; number subtraction; Stroop word-color conflict) | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | Plasma catecholamine levels at baseline and following MS tests | RH-PAT following MS was lower in patients with ABS vs with post-menopausal controls (P<.05) | Catecholamine levels were increased in patients with ABS vs in post-menopausal controls, following MS testing (P<.05) |
| PAT measurements during MS compared with baseline | Stress PAT ratios were lower in patients with ABS vs with patients with MI and post-menopausal controls (P<.05) | |||||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | No differences in stress PAT ratio in patients with MI vs post-menopausal controls | |||||||
| 87 | 2011 | 25 (6) | Healthy subjects | Three different MS tasks of 6-min duration in random order (number-letter recall challenge of increasing length and complexity; number subtraction; Stroop word-color conflict) | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | Arterial blood pressure signal amplitude using cuff attached to a pressure transducer (BIOPAC MP150 systems technology — a standard polygraph device used to detect deception during polygraph examinations in military or law enforcement applications) | No significant difference in RH-PAT and BIOPAC arterial blood pressure signal amplitude at rest or following MS (1.55±0.36 and 1.48±0.19; P=.38 and 1.44±0.29 and 1.47±0.21; P)=.61, respectively) | Lower stress PAT ratio vs BIOPAC stress ratio during each of the 3 MS tasks |
| PAT measurements during MS compared with baseline | Ratio of BIOPAC arterial blood pressure signal amplitude during MS to baseline arterial blood pressure signal amplitude | No differences in RH-PAT ratios between male and female subjects (P=.75) | No difference in stress PAT ratios between male and female subjects (P> .05) | |||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | ||||||||
| 88 | 2011 | 241 (126) | Healthy adolescents (mean age, 10 y) | Three different MS tasks of 6-min duration in random order (number-letter recall challenge of increasing length and complexity; number subtraction; Stroop word-color conflict) | PAT measurements during MS compared with baseline | Physical activity using a self-report questionnaire | In response to MS, male adolescents had a more vasoconstrictive response, followed by a less vasodilatory response, and needed longer time to return to baseline level than females | Adolescents who reported decreased physical activity over a 3-y period had increased arterial stiffness |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | ||||||||
| 89 | 2013 | 384 (159) | Patients with angiographically documented CAD | Standardized public speaking task | PAT measurements during MS compared with baseline | 99mTc-sestamibi MPI at rest and following both MS and physical stress testing, performed on separate days | Stress PAT ratio was lower in those with vs without MSIMI on MPI (0.55±0.36 vs 0.76±0.52; P=.009) | CAD severity and extent scores were not significantly different between those with or without MSIMI, whereas they were greater in those with compared with without physical stress induced ischemia (P<.04 for all) |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | In a multivariable analysis, stress PAT ratio was the only independent predictor of MSIMI on MPI (P=.009) | Angiographic severity and extent of CAD independently predicted physical stress induced myocardial ischemia | ||||||
| 90 | 2017 | 660 (482) | Patients with established stable CAD | Standardized public speaking task | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | 99mTc sestamibi MPI at rest, with MS, and with conventional (exercise/pharmacological) stress | 106 (16.1%) developed MSIMI, and 229 (34.7%) had conventional stress-induced myocardial ischemia | Only presence of ischemia during conventional stress (OR, 7.1; 95% CI, 4.2-11.9), high hemodynamic response (OR for RPP response ≥ vs < ROC cutoff of 1.8; 95% CI, 1.1-2.8), and high digital vasoconstriction (OR for stress PAT ratio < vs ≥ ROC cutoff of 2.1; 95% CI, 1.3-3.3) were independent predictors of MSIMI |
| Pulse wave velocity using PAT measurements | Rate-pressure-product (heart rate × systolic blood pressure) epinephrine levels | MS was associated with increases in SBP, DBP, HR, epinephrine levels, PWV, and significant decreases in FMD and stress PAT ratio denoting microvascular constriction | ||||||
| PAT measurements during MS compared with baseline | Patients with vs without MSIMI had higher hemodynamic and digital vasoconstrictive responses (P<.05 for both), but did not differ in epinephrine, endothelial (RH-PAT after MS) or macrovascular (FMD) responses | |||||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | ||||||||
| Endothelium-dependent FMD before and after MS | ||||||||
| 76 | 2018 | 62 (0) | 41 patients with coronary vascular dysfunction and 21 controls | Anger recall, mental arithmetic, and forehead cold pressor challenge | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | Emotional arousal was measured (Likert scale) | During MS 10% of controls reported chest pain vs 41% of subjects with coronary vascular dysfunction (P=.01) | Vasoconstriction inversely correlated with anxiety (r=-3.4, P=.03), frustration (r=-0.37, P=.02), and feeling challenged (r=-0.37, P=.02) in patients with coronary vascular dysfunction only |
| PAT measurements during MS compared with baseline | RH-PAT did not change significantly after MS in either group | |||||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Subjects with coronary vascular dysfunction had lower stress PAT ratios vs controls during mental arithmetic (0.54; 95% CI, 0.15-1.46 vs 0.67; 95% CI, 0.36-1.8; P=.039), not evident in the other tasks | |||||||
| 91 | 2018 | 418 (210) | 306 (150 females) subjects who were hospitalized for MI in the previous 8 months | Standardized public speaking task | RH-PAT at baseline (baseline PEF) compared with RH-PAT following MS (post-MS PEF) | 99mTc-sestamibi MPI at rest, with MS and conventional (exercise/pharmacological) stress | Women in both groups showed a higher stress PAT ratio and a lower RH-PAT index after MS indicating enhanced microvascular dysfunction after MS | Rate of MSIMI was twice as high in women as in men (22% vs 11%, P=.009), and ischemia with conventional stress was similarly elevated (31% vs 16%, P=.002) |
| 112 community controls (58 females) frequency matched for sex and age | PAT measurements during MS compared with baseline | No sex differences in FMD with MS | Stress PAT ratio and RH-PAT index after MS were predictive of MSIMI in women only | |||||
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | ||||||||
| Endothelium-dependent FMD before and after MS | ||||||||
| 92 | 2018 | 678 (492) | Patients with established stable CAD | Standardized public speaking task | PAT measurements during MS compared with baseline | MPI before and during MS | Women (but not men) with vs without MSIMI had a significantly lower stress PAT ratio (0.5 vs 0.8) | Men (but not women) with vs without MSIMI had a higher rate-pressure product response (6500 vs 4800 mm Hg beats/min) |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | SBP × HR – rate pressure product | Each 0.10-U decrease in stress PAT ratio was associated with 0.23% (95% CI, 0.11-0.35) increase in inducible myocardial ischemia in women | Each 1000-U increase in rate-pressure product response was associated with 0.32% (95% CI, 0.22-0.42) increase in inducible ischemia among men | |||||
| Ratios <1 indicate vasoconstrictive response | ||||||||
| 75 | 2018 | 38 (32) | Patients with stable CAD defined by an abnormal coronary angiogram demonstrating angiographic evidence of atherosclerosis with at least luminal irregularities | Mental arithmetic testing | PAT measurements during MS compared with baseline | Invasive endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS | MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by median, -5.9%; IQR, -0.5% to -2.6%; P=.001, without changing CBF | Stress PAT ratio correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=.004) |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=NS) | |||||||
| MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38; P=.03) but not with the response to nitroprusside | ||||||||
| 93 | 2019 | 18 (0) | 8 females with a history of ABS; 10 post-menopausal controls | Three different MS tasks of 6-min duration in random order (number-letter recall challenge of increasing length and complexity; number subtraction; Stroop word-color conflict) | PAT measurements during MS compared with baseline | Pain induced PAT ratio | Stress PAT ratio was lower in | Pain-induced PAT ratios were attenuated in patients with ABS: |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | patients with ABS: Stroop test (0.79±0.30 vs 1.24±0.43; P=.01); | at baseline (0.94±0.08 vs 1.30±0.54; P<.05); and post-MS (0.87±0.19 vs 1.24±0.21; P=.01) | ||||||
| Arithmetic test (0.91±0.27 vs 1.36±0.57, P=.01). | Pain-induced PAT ratios correlated significantly with stress PAT ratios, both in arithmetic and Stroop test (P<.05) | |||||||
| 94 | 2019 | 59 (44) | Patients with a history of stable CAD | Mental arithmetic testing, and public speaking stressors | PAT measurements during MS compared with baseline | PET imaging of the brain | Stress response ratios below the median were associated with increased stress activation in insula and parietal cortex, and decreased activation in the medial prefrontal cortex with MS tasks compared with control tasks | |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | ||||||||
| 95 | 2020 | 486 (350) | Patients with stable coronary atherosclerosis | Series of standardized speech/arithmetic stressors | PAT measurements during MS compared with baseline | 99mTc-sestamibi MPI at rest, with MS, and with conventional (exercise/pharmacological) stress | After multivariable adjustment MSIMI was associated with 21% and 20% slower completion of Trail-A and Trail-B, respectively (P for all <.01) | Ischemia with a conventional stress test was not associated with any of the cognitive tests over time |
| Stress PAT response ratio: pulse wave amplitude during MS/at baseline | Cognitive function assessed at baseline and at a 2-y follow-up using Trail Making Test parts A and B, and the verbal and visual memory subtests of the Wechsler Memory Scale | After a 2-y follow-up period, presence of MSIMI was associated with a 33% slower completion of Trail-B, denoting cognitive decline (B = 0.33; 95% CI, 0.04-0.62) | ||||||
| A lower stress PAT ratio, indicating greater vasoconstriction, mediated the association between MSIMI and worsening Trail-B performance by 18.2% |
a
ABS, apical ballooning syndrome; ACE-I, angiotensin-converting enzyme inhibitor; AUC, area under the curve; BP, blood pressure; CAD, coronary artery disease; CBF, coronary blood flow; CT, computed tomography; CV, cardiovascular; ECG, electrocardiogram; EDAD, endothelial-dependent arterial dilatation; EF, ejection fraction; ERNA, equilibrium radionucleotide angiocardiography; FMD, flow-mediated dilatation; GTN, sublingual glyceryl trinitrate; MI, myocardial infarction; MPI, myocardial perfusion imaging; MS, mental stress; MSIMI, mental stress–induced myocardial ischemia; NS, not significant; OR, odds ratio; PAT, peripheral arterial tonometry; PEF, peripheral endothelial function; PET, positron emission tomography; PWV, pulse wave velocity; RH-PAT, reactive hyperemia peripheral arterial tonometry; ROC, receiver operating characteristic curve; RPP, rate pressure product; SVR, systemic vascular resistance