Exercise Systolic Blood Pressure Response During Cycle Ergometry is Associated with Future Hypertension in Normotensive Individuals.

AIMS: We aimed to investigate the association between the exercise systolic blood pressure (SBP) response and future hypertension (HTN) in normotensive individuals referred for cycle ergometry, with special regard to reference exercise SBP values, and exercise capacity. METHODS: In this longitudinal cohort study, data from 14,428 exercise tests were cross-linked with Swedish national registries on diagnoses and medications. We excluded individuals with a baseline diagnosis of cardiovascular disease or HTN. The peak exercise SBP (SBPpeak) was recorded and compared to the upper limit of normal (ULN) derived from SBPpeak reference equations incorporating age, sex, resting SBP and exercise capacity. To evaluate the impact of exercise capacity, three SBP to work rate slopes (SBP/W-slopes), were calculated, relative to either supine or seated SBP at rest or to the first exercise SBP. Adjusted hazard ratios (HRadjusted [95% Confidence interval, CI]) for incident HTN during follow-up, in relation to SBP response metrics, were calculated. RESULTS: We included 3,895 normotensive individuals (49±14 years, 45% females) with maximal cycle ergometer tests. During follow-up (median 7.5 years) 22% developed HTN. Higher SBPpeak and SBPpeak>ULN were associated with incident HTN (HRadjusted 1.19 [1.14-1.23] per 10 mmHg, and 1.95 [1.54-2.47], respectively). All three SBP/W-slopes were positively associated to incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP (HRadjusted 1.25 [1.19-1.31] per 1 mmHg/10W). CONCLUSION: Both SBPpeak>ULN based on reference values and high SBP/W-slopes were associated with incident HTN in normotensive individuals and should be considered in the evaluation of the cycle ergometry SBP response.

We examined the systolic blood pressure response during maximal bicycle exercise testing in individuals without hypertension or established cardiovascular disease, and found that: When applying reference values for peak systolic blood pressure during cycling exercise, accounting for age, sex, resting blood pressure and exercise capacity, exceeding the upper limit of normal was associated with twice as high relative risk of future hypertension, compared to having a peak systolic blood pressure within normal limits. A steep increase in exercise blood pressure in relation to the increase in work rate was also associated with future hypertension but did not always coincide with elevated peak systolic blood pressure.

The modified Medical Research Council scale misclassifies exertional breathlessness among people referred for exercise testing.

Background: Exertional breathlessness is a major symptom in cardiorespiratory disease and is often assessed using the modified Medical Research Council (mMRC) questionnaire. The mMRC might underestimate exertional breathlessness in people with impaired exercise capacity who have reduced their physical activity to avoid the symptom. We aimed to evaluate the ability of mMRC to detect abnormally high exertional breathlessness or abnormally low exercise capacity during incremental cycle exercise testing (IET). Methods: A secondary analysis of data from a randomised controlled trial of outpatients aged 18 years or older referred for IET was carried out. Participants completed the mMRC before IET. Abnormally high exertional breathlessness was defined as a breathlessness (Borg 0-10) intensity response more than the upper limit of normal. Abnormally low exercise capacity was defined using published reference equations. The sensitivity, specificity, accuracy and discriminative ability of each mMRC rating to detect each outcomewas calculated. Results: 92 participants were included; the mean age was 59 years, 61% were male, and 64% and 15% had mMRC 1 and ≥2, respectively. An mMRC ≥2 had the highest accuracy (71%) to detect abnormally high exertional breathlessness, with a specificity of 93% but a sensitivity of only 28%, failing to identify 72% of people with abnormally high exertional breathlessness. The accuracy, specificity and sensitivity for abnormally low exercise capacity was 64%, 88% and 19%, respectively. Conclusion: Among people referred for clinical exercise testing, the mMRC dyspnoea scale misclassified exertional breathlessness and exercise capacity assessed using cycle IET, with substantial underdetection. A mMRC dyspnoea rating of 0-1 does not preclude the presence of abnormally high exertional breathlessness or abnormally low exercise capacity.

Reference equations for breathlessness during incremental cycle exercise testing.

Background: Exertional breathlessness is commonly assessed using incremental exercise testing (IET), but reference equations for breathlessness responses are lacking. We aimed to develop reference equations for breathlessness intensity during IET. Methods: A retrospective, consecutive cohort study of adults undergoing IET was carried out in Sweden. Exclusion criteria included cardiac or respiratory disease, death or any of the aforementioned diagnoses within 1 year of the IET, morbid obesity, abnormally low exercise capacity, submaximal exertion or an abnormal exercise test. Probabilities for breathlessness intensity ratings (Borg CR10) during IET in relation to power output (%predWmax), age, sex, height and body mass were analysed using marginal ordinal logistic regression. Reference equations for males and females were derived to predict the upper limit of normal (ULN) and the probability of different Borg CR10 intensity ratings. Results: 2581 participants (43% female) aged 18-90 years were included. Mean breathlessness intensity was similar between sexes at peak exertion (6.7±1.5 versus 6.4±1.5 Borg CR10 units) and throughout exercise in relation to %predWmax. Final reference equations included age, height and %predWmax for males, whereas height was not included for females. The models showed a close fit to observed breathlessness intensity ratings across %predWmax values. Models using absolute W did not show superior fit. Scripts are provided for calculating the probability for different breathlessness intensity ratings and the ULN by %predWmax throughout IET. Conclusion: We present the first reference equations for interpreting breathlessness intensity during incremental cycle exercise testing in males and females aged 18-90 years.

Peak exercise SBP and future risk of cardiovascular disease and mortality.

OBJECTIVES: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing. METHODS: Data from 10 096 clinical exercise tests (54% men, age 18-85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile. RESULTS: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59-2.52) in men and 2.60 (1.97-3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28-1.89, men) and 1.34 (1.05-1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22-0.54) and 0.72 (0.57-0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted. CONCLUSION: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity.

Age- and gender-specific upper limits and reference equations for workload-indexed systolic blood pressure response during bicycle ergometry.

BACKGROUND: Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking. DESIGN: This was a retrospective, consecutive cohort study. METHODS: From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from ≥ 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors. RESULTS: A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 ± 24 vs 202 ± 22 mmHg, p < 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 ± 0.21 versus 0.41 ± 0.15 mmHg/watt (p < 0.001); peak SBP/watt-ratio: 1.35 ± 0.34 versus 0.90 ± 0.21 mmHg/watt (p < 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations. CONCLUSIONS: These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males.

Typical angina during exercise stress testing improves the prediction of future acute coronary syndrome.

INTRODUCTION: The prognostic value of angina during exercise stress testing is controversial, possibly due to previous studies not differentiating typical from non-typical angina. We aimed to assess the prognostic value of typical angina alone, or in combination with ST depression, during exercise stress testing for predicting cardiovascular events. METHODS: We conducted a prospective observational cohort study including all patients who performed a clinical exercise stress test at the department of Clinical Physiology, Kalmar County Hospital between 2005 and 2012. The association between typical angina/ST depression and incident acute coronary syndrome (ACS) and cardiovascular mortality were analysed using Cox regression for long-term and 1-year follow-up. RESULTS: Out of 11605 patients (median follow-up 6.7 years), 623 (5.4%) developed ACS and 319 (2.7%) died from cardiovascular causes. Compared to patients with no angina and no ST depression, typical angina and ST depression were associated with increased risk of future ACS; hazard ratio (HR) 3.5 ([95%CI] 2.6-4.7). This association was even stronger for ACS within one year (typical angina with and without concomitant ST depression; HR 20.8 (13.9-31.3) and 9.7 (6.1-15.4), respectively). Concordance statistics for ST depression in predicting ACS during long-term follow-up was 0.58 (0.56-0.60) and 0.69 (0.65-0.73) for ACS within one year, and 0.64 (0.62-0.66) and 0.77 (0.73-0.81), respectively, when typical angina was added to the model. CONCLUSIONS: Typical angina during exercise stress testing is predictive of future ACS, especially in combination with ST depression, and during the first year after the test.

Effect of the trajectory of exertional breathlessness on symptom recall and anticipation: A randomized controlled trial.

BACKGROUND: Breathlessness is a major cause of physical limitation. Recalled breathlessness intensity may differ from experienced intensity and be influenced by the intensity trajectory including the 'peak-end rule'. The primary aim was to test if adding two minutes of low intensity exercise at the end of an exercise test would change the recalled breathlessness. Secondary aims included to analyse the impact of the peak and end exertional breathlessness intensity on breathlessness recall. METHODS: Randomized controlled trial of 92 adults referred for exercise testing who were randomized (1:1), at test end, to 2 minutes of additional low intensity exercise (intervention; n = 47) or stopping at peak exertion (control; n = 45). Experienced breathlessness during the test and recalled intensity (30 min after the test) was assessed using the Borg CR10 scale. RESULTS: Participants were aged a mean 59 years; 61% men; 79% reported a mMRC ≥1. There was no between-group difference in recalled breathlessness intensity, 5.51 ([95% CI] 5.00 to 6.01) vs. 5.73 (5.27 to 6.20; p = 0.52) in controls, even though the intervention group had a significantly lower end breathlessness (mean difference 0.96; 0.24 to 1.67; p = 0.009). Recalled exertional breathlessness was most strongly related to peak breathlessness (r2 = 0.43). When analyzed together, end breathlessness did not add any explanatory value above that of peak breathlessness. CONCLUSION: Adding an episode of two minutes of lower exercise and breathlessness intensity at the end of an exercise test did not affect symptom recall, which was most strongly related to peak breathlessness intensity. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03468205).

Long-term follow-up of patients undergoing standardized bicycle exercise stress testing: new recommendations for grading of exercise capacity are clinically relevant.

INTRODUCTION: A new grading of exercise capacity during bicycle stress testing has been proposed in Sweden based on the new reference material ('the Kalmar material'), which has not been validated. We aimed to examine the prognostic information of the new grading of exercise capacity during exercise stress testing. METHODS: Data on all bicycle exercise tests performed at the Department of Clinical Physiology in Kalmar between May 2005 and October 2016 were cross-linked with the Causes of Death Register (until 30 April 2019) and the National Patient Register (until 12 December 2017). Exercise capacity was graded based on predicted exercise capacity: ≥120% (good), 75 to <120% (normal), 70 to <75% (mildly reduced), 50 to <70% (moderately reduced) and <50% (severely reduced). Associations with all-cause mortality, cardiovascular mortality and hospitalization for ischaemic heart disease (IHD) and heart failure were analysed using Cox regression. RESULTS: A total of 13 887 patients were followed a median of 7·7 years (interquartile range 5·0-10·8); 1809 patients died (546 from cardiovascular disease). Compared to normal exercise capacity, reduction of exercise capacity was strongly associated with increased all-cause mortality [(hazard ratio; 95% confidence interval): mild (3·0; 2·6-3·5); moderate (4·4; 3·9-4·9); and severe reduction (8·5; 7·2-10·0)]. Reduced exercise capacity was also associated with increased risks of cardiovascular hospitalization and mortality. CONCLUSION: Reduced exercise capacity is associated with increased all-cause and cardiovascular mortality, as well as increased risk of future IHD and heart failure diagnosis and hospitalization. In patients with reduced exercise capacity, mortality is progressively increased with worsening grade of exercise capacity.

Ischemic QRS prolongation as a biomarker of myocardial injury in STEMI patients.

BACKGROUND: Patients with acute coronary occlusion (ACO) may not only have ischemia-related ST-segment changes but also changes in the QRS complex. It has recently been shown in dogs that a greater ischemic QRS prolongation (IQP) during ACO is related to lower collateral flow. This suggests that greater IQP could indicate more severe ischemia and thereby more rapid infarct development. Therefore, the purpose was to evaluate the relationship between IQP and measures of myocardial injury in patients presenting with acute ST-elevation myocardial infarction (STEMI). METHODS: Seventy-seven patients with first-time STEMI were retrospectively included from the recently published SOCCER trial. All patients underwent a cardiac magnetic resonance (CMR) examination 2-6 days after the acute event. Infarct size (IS), myocardium at risk (MaR), and myocardial salvage index (MSI) were assessed and related to IQP. IQP measures assessed were; computer-generated QRS duration, QRS duration at maximum ST deviation, absolute IQP and relative IQP, all derived from a pre-PCI, 12-lead ECG. RESULTS: Median absolute IQP was 10 ms (range 0-115 ms). There were no statistically significant correlations between measures of IQP and any of the CMR measures of myocardial injury (absolute IQP vs IS, r = 0.03, p = 0.80; MaR, r = -0.01, p = 0.89; MSI, r = -0.05, p = 0.68). CONCLUSIONS: Unlike previous experimental studies, the IQP was limited in patients presenting at the emergency room with first-time STEMI and no correlation was found between IQP and CMR variables of myocardial injury in these patients. Therefore, IQP does not seem to be a suitable biomarker for triaging patients in this clinical context.

A 12-lead ECG-method for quantifying ischemia-induced QRS prolongation to estimate the severity of the acute myocardial event.

INTRODUCTION: Studies have shown terminal QRS distortion and resultant QRS prolongation during ischemia to be a sign of low cardiac protection and thus a faster rate of myocardial cell death. A recent study introduced a single lead method to quantify the severity of ischemia by estimating QRS prolongation. This paper introduces a 12-lead method that, in contrast to the previous method, does not require access to a prior ECG. METHODS: QRS duration was estimated in the lead that showed the maximal ST deviation according to a novel method. The degree of prolongation was determined by subtracting the measured QRS duration in the lead that showed the least ST deviation. RESULTS: The method is demonstrated in examples of acute occlusion in two of the major coronary arteries. CONCLUSION: This paper presents a 12-lead method to quantify the severity of ischemia, by measuring QRS prolongation, without requiring comparison with a previous ECG.