Machine learning models for assessing risk factors affecting health care costs: 12-month exercise-based cardiac rehabilitation.

Introduction: Exercise-based cardiac rehabilitation (ECR) has proven to be effective and cost-effective dominant treatment option in health care. However, the contribution of well-known risk factors for prognosis of coronary artery disease (CAD) to predict health care costs is not well recognized. Since machine learning (ML) applications are rapidly giving new opportunities to assist health care professionals' work, we used selected ML tools to assess the predictive value of defined risk factors for health care costs during 12-month ECR in patients with CAD. Methods: The data for analysis was available from a total of 71 patients referred to Oulu University Hospital, Finland, due to an acute coronary syndrome (ACS) event (75% men, age 61 ± 12 years, BMI 27 ± 4 kg/m2, ejection fraction 62 ± 8, 89% have beta-blocker medication). Risk factors were assessed at the hospital immediately after the cardiac event, and health care costs for all reasons were collected from patient registers over a year. ECR was programmed in accordance with international guidelines. Risk analysis algorithms (cross-decomposition algorithms) were employed to rank risk factors based on variances in their effects. Regression analysis was used to determine the accounting value of risk factors by entering first the risk factor with the highest degree of explanation into the model. After that, the next most potent risk factor explaining costs was added to the model one by one (13 forecast models in total). Results: The ECR group used health care services during the year at an average of 1,624 ± 2,139€ per patient. Diabetes exhibited the strongest correlation with health care expenses (r = 0.406), accounting for 16% of the total costs (p < 0.001). When the next two ranked markers (body mass index; r = 0.171 and systolic blood pressure; r = - 0.162, respectively) were added to the model, the predictive value was 18% for the costs (p = 0.004). The depression scale had the weakest independent explanation rate of all 13 risk factors (explanation value 0.1%, r = 0.029, p = 0.811). Discussion: Presence of diabetes is the primary reason forecasting health care costs in 12-month ECR intervention among ACS patients. The ML tools may help decision-making when planning the optimal allocation of health care resources.

The Impact of Multimorbidity Patterns on Changes in Physical Activity and Physical Capacity Among Older Adults Participating in a Year-Long Exercise Intervention.

This study investigated the impact of multimorbidity patterns on physical activity and capacity outcomes over the course of a year-long exercise intervention, and on physical activity 1 year later. Participants were 314 physically inactive community-dwelling men and women aged 70-85 years, with no contraindications for exercise at baseline. Physical activity was self-reported. Physical capacity measurements included five-time chair-stand time, 6-minute walking distance, and maximal isometric knee-extension strength. The intervention included supervised and home-based strength, balance, and walking exercises. Multimorbidity patterns comprised physician-diagnosed chronic disease conditions as a predictor cluster and body mass index as a measure of obesity. Multimorbidity patterns explained 0%-12% of baseline variance and 0%-3% of the change in outcomes. The magnitude and direction of the impact of unique conditions varied by outcome, time point, and sex. Multimorbid older adults with no contraindications for exercise may benefit from multimodal physical training.

Baroreflex sensitivity following acute upper-body exercise in the cold among stable coronary artery disease patients.

Background: A cold environment and exercise separately affect the autonomic nervous system (ANS), baroreflex sensitivity (BRS), and blood pressure variability (BPV) but their combined effects on post-exercise recovery are not known. Our cross-over trial examined these responses following upper-body static and dynamic exercise performed in a cold and neutral environment in patients with coronary artery disease (CAD). Methods: 20 patients with stable coronary artery disease performed both graded static (10%-30% of maximal voluntary contraction) and dynamic (light, moderate and high perceived intensity) upper-body exercise at -15°C and +22°C for 30 min. Electrocardiogram and continuous blood pressure were measured to compute post-exercise (10 and 30 min after exercise) spectral powers of heart rate (HR), blood pressure variability and BRS at low (0.04-0.15 Hz) and high (0.15-0.4 Hz) frequencies. Results: Static upper-body exercise performed in a cold environment increased post-exercise high frequency (HF) spectral power of heart rate (HF RR) (p < 0.001) and reduced heart rate (p = 0.001) and low-to-high frequency (LF/HF) ratio (p = 0.006) more than in a neutral environment. In addition, post-exercise mean BRS (p = 0.015) and high frequency BRS (p = 0.041) increased more following static exercise in the cold than in a neutral environment. Dynamic upper-body exercise performed in a cold environment reduced post-exercise HF BRS (p = 0.019) and systolic blood pressure (p = 0.003). Conclusion: Static upper-body exercise in the cold increased post-exercise BRS and overall vagal activity but without reduced systolic blood pressure. Dynamic upper-body exercise in the cold reduced post-exercise vagal BRS but did not affect the other parameters. The influence of cold exposure on post-exercise autonomic and cardiovascular responses following static upper-body exercise require further studies. This information helps understanding why persons with cardiovascular diseases are vulnerable to low environmental temperature. ClinicalTrials.gov: NCT02855905 (04/08/2016).

Cardiac Autonomic Function and Functional Capacity in Post-COVID-19 Individuals with Systemic Arterial Hypertension.

Individuals diagnosed with systemic arterial hypertension (SAH) are considered risk groups for COVID-19 severity. This study assessed differences in cardiac autonomic function (CAF) and functional capacity (FC) in SAH individuals without COVID-19 infection compared to SAH individuals post-COVID-19. Participants comprised 40 SAH individuals aged 31 to 80 years old, grouped as SAH with COVID-19 (G1; n = 21) and SAH without COVID-19 (G2; n = 19). CAF was assessed via heart rate variability (HRV), measuring R-R intervals during a 10-min supine period. Four HRV indices were analyzed through symbolic analysis: 0V%, 1V%, 2LV%, and 2UV%. FC assessment was performed by a 6-min walk test (6MWT). G1 and G2 showed no significant differences in terms of age, anthropometric parameters, clinical presentation, and medication use. G2 exhibited superior 6MWT performance, covering more distance (522 ± 78 vs. 465 ± 59 m, p < 0.05). Specifically, G2 demonstrated a moderate positive correlation between 6MWT and the 2LV% index (r = 0.58; p < 0.05). Shorter walking distances were observed during 6MWT in SAH individuals post-COVID-19. However, the study did not find impaired cardiac autonomic function in SAH individuals post-COVID-19 compared to those without. This suggests that while COVID-19 impacted FC, CAF remained relatively stable in this population.

Machine learning models in predicting health care costs in patients with a recent acute coronary syndrome: A prospective pilot study.

Background: Health care budgets are limited, requiring the optimal use of resources. Machine learning (ML) methods may have an enormous potential for effective use of health care resources. Objective: We assessed the applicability of selected ML tools to evaluate the contribution of known risk markers for prognosis of coronary artery disease to predict health care costs for all reasons in patients with a recent acute coronary syndrome (n = 65, aged 65 ± 9 years) for 1-year follow-up. Methods: Risk markers were assessed at baseline, and health care costs were collected from electronic health registries. The Cross-decomposition algorithms were used to rank the considered risk markers based on their impacts on variances. Then regression analysis was performed to predict costs by entering the first top-ranking risk marker and adding the next-best markers, one by one, to build up altogether 13 predictive models. Results: The average annual health care costs were €2601 ± €5378 per patient. The Depression Scale showed the highest predictive value (r = 0.395), accounting for 16% of the costs (P = .001). When the next 2 ranked markers (LDL cholesterol, r = 0.230; and left ventricular ejection fraction, r = -0.227, respectively) were added to the model, the predictive value was 24% for the costs (P = .001). Conclusion: Higher depression score is the primary variable forecasting health care costs in 1-year follow-up among acute coronary syndrome patients. The ML tools may help decision-making when planning optimal utilization of treatment strategies.

Standing time and daily proportion of sedentary time are associated with pain-related disability in a one month accelerometer measurement in adults with overweight or obesity.

OBJECTIVES: The association between the subjective experience of pain-related disability (PRD) and device-measured physical activity (PA) and sedentary behavior (SB) in overweight and obese adults is not well known. The aim of this study was to investigate the associations of pain markers with accelerometer-measured SB duration and different intensities of PA among physically inactive middle-aged adults with overweight or obesity. METHODS: This cross-sectional analysis included 72 subjects (27 men) with mean age of 57.9 (SD 6.7) years and mean BMI of 31.6 (SD 4.1) kg/m2. SB and standing time (ST), breaks in sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were measured for four consecutive weeks (mean 25 days, SD 4) with a hip-worn triaxial accelerometer. Headache, musculoskeletal pain, back pain, and PRD were assessed by visual analog scales (VAS) and using the Oswestry disability index (ODI). RAND-36 questionnaire was applied to assess health-related quality of life. The associations were studied by linear models. RESULTS: ST was positively and SB proportion was negatively associated with PRD when adjusted for age, sex, BMI, accelerometry duration, MVPA, pain medication use, and general health perceptions assessed by RAND-36. No associations were found between ST and back pain. SB or different PA intensities were not associated with pain experience at specific sites. CONCLUSIONS: Longer daily ST, but not LPA or MVPA is associated with higher level of PRD. Correspondingly, higher proportion of SB is associated with lower level of PRD. This suggests that individuals with PRD prefer to stand, possibly to cope with pain. These results may highlight the importance of habitual standing behaviors in coping with experienced PRD in adults with overweight or obesity.

Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up.

BACKGROUND: Long-term effects of Coronavirus Disease of 2019 (COVID-19) are of utmost relevance. We aimed to determine: 1) the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2) the characteristics associated with cardiopulmonary exercise testing (CPET) performance; 3) the safety and tolerability of CPET. METHODS: We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 from Azienda Sanitaria Locale 3, Genoa. Three months after hospital discharge a complete clinical evaluation, trans-thoracic echocardiography, CPET, pulmonary function tests, and dominant leg extension (DLE) maximal strength measurement were performed. RESULTS: From the 225 patients discharged alive from March to November 2020, we excluded 12 incomplete/missing cases and 13 unable to perform CPET, leading to a final cohort of 200. Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3-103.1). Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value. Among the 99 patients with reduced %pVO2, 61 (61%) had a normal anaerobic threshold: of these, 9(14.8%) had respiratory, 21(34.4%) cardiac, and 31(50.8%) non-cardiopulmonary reasons for exercise limitation. Inerestingly, 80% of patients experienced at least one disabling symtpom, not related to %pVO2 or functional capacity. Multivariate linear regression showed percent-predicted forced expiratory volume in one-second(ß = 5.29,p = 0.023), percent-predicted diffusing capacity of lungs for carbon monoxide(ß = 6.31,p = 0.001), and DLE maximal strength(ß = 14.09,p = 0.008) to be independently associated with pVO2. No adverse event was reported during or after CPET, and no involved health professional developed COVID-19. CONCLUSIONS: At three months after discharge, about 1/3rd of COVID-19 survivors show functional limitations, mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.

Good safety practice in a randomized controlled trial (CadColdEx) involving increased cardiac workload in patients with coronary artery disease.

BACKGROUND: Methodological information acknowledging safety of cardiac patients in controlled medical experiments are lacking. The descriptive report presents one good practice for considering safety in a randomized controlled study involving augmented cardiovascular strain among persons with coronary artery disease (CAD). METHODS: The patients were pre-selected by a cardiologist according to strictly defined selection criteria. Further confirmation of eligibility included screening of health. In addition, assessments of physical capacity by a graded bicycle ergometer test were implemented and safety monitored by an exercise physiologist and medical doctor. In this context, an emergency simulation was also carried out. A total of 18 CAD patients each underwent four different experimental interventions where either temperature (+ 22 °C and - 15 °C) and the level of exercise (rest and brisk walking) were employed for 30 min in random order (72 experiments). Baseline (20 min) and follow-up (60 min) measurements were conducted resting at + 22 °C. ECG, and brachial blood pressure were measured and perceived exertion and symptoms of chest pain inquired throughout the experiments. An emergency nurse was responsible for the health monitoring and at least two persons followed the patient throughout the experiment. A medical doctor was available on call for consultation. The termination criteria followed the generally accepted international guidelines for exercise testing and were planned prior to the experiments. RESULTS: The exercise test simulation revealed risks requiring changes in the study design and emergency response. The cardiovascular responses of the controlled trials were related to irregular HR, ST-depression or post-exercise hypotension. These were expected and the majority could be dealt on site by the research personnel and on call consultation. Only one patient was encouraged to seek for external health care consultation. CONCLUSIONS: Appropriate prospective design is a key to safe implementation of controlled studies involving cardiac patients and stimulation of cardiovascular function. This includes careful selection of participants, sufficient and knowledgeable staff, as well as identifying possible emergency situations and the required responses. TRIAL REGISTRATION: ClinicalTrials ID: NCT02855905 .

Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life.

BACKGROUND: Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. METHODS: At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965-1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. RESULTS: In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500-3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). CONCLUSIONS: In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth weight in males may contribute to less favourable cardiovascular autonomic regulation and potentially to an elevated cardiovascular risk in later life.

Exercise capacity and mortality - a follow-up study of 3033 subjects referred to clinical exercise testing.

BACKGROUND: Exercise stress testing is used as a diagnostic and prognostic tool. We determined the prognostic significance of exercise test findings for cardiovascular (CVD) and all-cause mortality in men and women. MATERIAL AND METHODS: 3033 subjects underwent a symptom-limited bicycle exercise test. Exercise capacity was defined as the mean of last four minutes of exercise workload. RESULTS: During an average follow-up of 19 years, 186 (11.6%) CVD and 370 (20.6%) all-cause deaths in men and 57 (5.0%) CVD and 155 (12.5%) all-cause deaths in women occurred. Among exercise test variables (workload, ECG, BP, HR), exercise capacity was the strongest predictor of mortality. Low exercise capacity (1st quartile) was associated with a hazard ratio of 4.2 (95% CI: 1.7, 10.8) for CVD and 4.0 (95% CI: 2.5, 6.4) for all-cause mortality compared with high exercise capacity (4th quartile) among men and in women with a 5.4-fold (95% CI: 1.2, 24.0) risk for CVD and 2.3-fold (95% CI: 1.2, 4.3) risk for all-cause mortality, respectively. The relationship between other exercise test variables and mortality was much weaker. CONCLUSIONS: Among exercise test variables exercise capacity was the strongest predictor of CVD and all-cause mortality in both genders, and especially CVD deaths in women. Key Messages Exercise capacity was the most powerful predictor of CVD and all-cause mortality in both men and women. Low exercise capacity is a strong predictor of CVD death, especially among women.

Lifelong Physical Activity and Cardiovascular Autonomic Function in Midlife.

PURPOSE: Physical activity (PA) associates with cardiovascular autonomic function, but the relationship with lifelong PA is unclear. We hypothesized that lifelong PA would associate with cardiovascular autonomic function in midlife. METHODS: At the age of 46 yr, the subjects of the prospective Northern Finland Birth Cohort 1966 were invited to examinations where vagally mediated heart rate variability (root mean square of the successive differences in RRi [rMSSD]) and cross-spectral baroreflex sensitivity (BRS) were analyzed from 3-min recordings of ECG and blood pressure in seated and standing positions. Three lifelong PA trajectory groups (active, semiactive, and inactive) were formed according to their self-reported frequencies of participation in PA at the ages of 14, 31, and 46 yr. Finally, 1283 men and 1779 women without cardiorespiratory diseases and diabetes had complete data on lifelong PA, covariates, and rMSSD, and 662 men and 807 women for BRS. RESULTS: In both sexes and measurement conditions, the active (P < 0.01) and semiactive groups (P < 0.05) had greater rMSSD than the inactive group, and the highest BRS was observed in the active group (ANOVA P = 0.001-0.032). In men, these differences were not significant when adjusted for 46-yr lifestyle (smoking, alcohol consumption, sleep, and sitting time), body mass index, waist-to-hip ratio, blood pressure, lipid status, and glucose status. In women, lifelong PA remained a significant independent determinant of seated and standing rMSSD and standing BRS. CONCLUSION: Higher lifelong PA was associated with better cardiovascular autonomic function in midlife. In women, this effect was independent, but in men, it seemed to be mediated by the other lifestyle and cardiometabolic factors.

Short-term assessment of autonomic nervous system as a potential tool to quantify pain experience.

Various pain conditions may result in altered autonomic nervous system regulation. We evaluated whether autonomic regulation, analyzed with short-term heart rate variability (HRV), differs between low back pain (LBP) patients and healthy controls. Additionally, we tested if short-term HRV recordings are feasible and informative in planning home monitoring of LBP patients. The study population consisted of 16 volunteers (8 LBP patients and 8 healthy subjects) (age 42±10 years, body mass index 26±4 kg/m2, 7 men and 9 women). Usually 3- to 5-minute R-R interval recordings have been used as short-term recordings of HRV, but recent evidence supports even shorter R-R interval recording procedure for short-term HRV assessment. We collected R-R interval data for 1 minute in sitting, standing and bending down tasks. Mean heart rate (HR) and vagally mediated beat-to-beat variability (SD1 and rMSSD) were analyzed. The results showed that autonomic nervous system function assessed with the short-term measurement HRV method differentiates LBP patients from healthy controls in sitting and standing. Vagally mediated SD1 and rMSSD were significantly lower and the HR was higher among the patients compared to the controls. A novel finding was also the feasibility of 1-minute measurement of HRV, which may open entirely new opportunities to assess accurately concomitant changes in autonomic nervous system function and self-reported individual pain experience. This could lead to a more personalized pain treatment and more efficient health care resource allocation as the new measurement methods is more suitable for home monitoring than the previously used ones.

Exercise capacity and heart rate responses to exercise as predictors of short-term outcome among patients with stable coronary artery disease.

Although exercise capacity (EC) and autonomic responses to exercise predict clinical outcomes in various populations, they are not routinely applied in patients with coronary artery disease (CAD). We hypothesized that the composite index of EC and exercise heart rate responses would be a powerful determinant of short-term risk in CAD. Patients with angiographically documented stable CAD and treated with ß blockers (n = 1,531) underwent exercise testing to allow the calculation of age- and gender-adjusted EC, maximal chronotropic response index (CRI), and 2-minute postexercise heart rate recovery (HRR, percentage of maximal heart rate). Cardiovascular deaths and hospitalization due to heart failure, registered during a 2-year follow-up (n = 39, 2.5%), were defined as the composite primary end point. An exercise test risk score was calculated as the sum of hazard ratios related to abnormal (lowest tertile) EC, CRI, and HRR. Abnormal EC, CRI, and HRR predicted the primary end point, involving 4.5-, 2.2-, and 6.2-fold risk, respectively, independently of each other. The patients with intermediate and high exercise test risk score had 11.1-fold (95% confidence interval 2.4 to 51.1, p = 0.002) and 25.4-fold (95% confidence interval 5.5 to 116.8, p <0.001) adjusted risk for the primary end point in comparison with the low-risk group, respectively. The addition of this risk score to the established risk model enhanced discrimination by integrated discrimination index and reclassification by categorical and continuous net reclassification index (p <0.001 for all). In conclusion, the composite index of EC and heart rate responses to exercise and recovery is a powerful predictor of short-term outcome in patients with stable CAD.

Effects of physical activity and exercise training on cardiovascular risk in coronary artery disease patients with and without type 2 diabetes.

OBJECTIVE: Leisure-time physical activity (LTPA) and exercise training are essential parts of current guidelines for patients with coronary artery disease (CAD). However, the contributions of LTPA and exercise training to cardiovascular (CV) risk in CAD patients with type 2 diabetes (T2D) are not well established. RESEARCH DESIGN AND METHODS: We examined the effects of LTPA (n = 539 and n = 507; with and without T2D, respectively) and 2-year controlled, home-based exercise training (n = 63 plus 64 control subjects with T2D and n = 72 plus 68 control subjects without T2D) on the CV risk profile and composite end point among CAD patients. RESULTS: During the 2-year follow-up, patients with reduced LTPA at baseline had an increased risk of CV events (adjusted hazard ratio 2.3 [95% CI 1.1-5.1; P = 0.033], 2.1 [1.1-4.2; P = 0.027], and 2.0 [1.0-3.9; P = 0.044] for no LTPA, LTPA irregularly, and LTPA two to three times weekly, respectively) compared with those with LTPA more than three times weekly. Among patients who completed the 2-year exercise intervention, exercise training resulted in favorable changes in exercise capacity both in CAD patients with T2D (+0.2 ± 0.8 vs. -0.1 ± 0.8 MET, P = 0.030) and without T2D (+0.3 ± 0.7 vs. -0.1 ± 0.5 MET, P = 0.002) as compared with the control group but did not have any significant effects on major metabolic or autonomic nervous system risk factors in CAD patients with or without T2D. CONCLUSIONS: There is an inverse association between habitual LTPA and short-term CV outcome, but controlled, home-based exercise training has only minor effects on the CV risk profile in CAD patients with T2D.

Impact and management of physiological calibration in spectral analysis of blood pressure variability.

Physiological calibration (Physiocal) improves the quality of continuous blood pressure (BP) signal from finger. However, the effects of Physiocal on spectral characteristics of systolic BP (SBP) variability are not well-known. We tested the hypothesis that the use of Physiocal may alter the results on SBP variability when compared with BP recording without Physiocal. Continuous BP was recorded simultaneously from fingers of both arms during 10-min standing by two Nexfin devices, one with (ON) and the other without (OFF) Physiocal (n = 19). Missing SBP values in ON signal were linearly interpolated over Physiocal sequences (ONinter). The OFF signal was analyzed without any corrections (OFFreference) and after linear interpolation of corresponding sequences when Physiocal appeared in the ON signal (OFFinter). Mean low frequency power of SBP oscillations (LFSBP, 0.04-0.15 Hz) did not differ between the OFFreference, OFFinter, and ONinter. However, LFSBP deviated more from OFFreference when analyzed from ONinter compared with the analysis from OFFinter [median (interquartile range): 14.7 (4.6-38.6) vs. 0.9 (0.5-1.8) %, p < 0.05]. In conclusion, the use of Physiocal had a significant effect on the spectral SBP variability that overwhelms the impact of linear interpolation of short data sequences. Therefore, caution is needed when comparing SBP variability between BP datasets acquired with and without Physiocal.

Effects of exercise rehabilitation on cardiac electrical instability assessed by T-wave alternans during ambulatory electrocardiogram monitoring in coronary artery disease patients without and with diabetes mellitus.

Effects of exercise rehabilitation on electrocardiographic markers of risk for sudden cardiac death have not been adequately studied. We examined effects of controlled exercise training on T-wave alternans (TWA) in 24-hour ambulatory electrocardiogram recordings in patients with stable coronary artery disease (CAD) without and with type 2 diabetes mellitus (DM). Consecutive patients with angiographically confirmed CAD were recruited to join the ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) study. Exercise (n = 65) and control groups (n = 65) were matched on age, sex, DM, and previous myocardial infarction. Ambulatory electrocardiograms were recorded before and after a 2-year training period. TWA was assessed using time domain-modified moving average method by an investigator blinded to patients' clinical status. Average TWA values decreased in the rehabilitation group but not in control patients (rehabilitation [mean ± SEM]: 52.8 ± 1.7 µV vs 48.7 ± 1.5 µV, p <0.001; control: 53.7 ± 1.7 µV vs 54.3 ± 1.6 µV, p = 0.746). Changes in TWA differed between the groups (rehabilitation: -4.1 ± 1.2 µV vs controls: +0.6 ± 1.1 µV, p = 0.005). In CAD + DM patients, 50% (n = 9) of the 18 positive TWA cases were converted with exercise versus 10% (n = 2 of 20) of controls (p = 0.020). In CAD patients, 30% (n = 8 of 27) of positive TWA cases were converted with exercise versus 4% (n = 1 of 28) of controls (p = 0.012). In conclusion, this is the first report of the effectiveness of exercise rehabilitation to reduce TWA, a marker of sudden cardiac death risk, in patients with stable CAD.

Prognostic significance of impaired baroreflex sensitivity assessed from Phase IV of the Valsalva maneuver in a population-based sample of middle-aged subjects.

Depressed baroreflex sensitivity (BRS) is associated with an increased risk of mortality in patients with a known cardiac disease. The prognostic significance of BRS in subjects without history of major cardiovascular (CV) events is unknown. The present study tested the hypothesis that impaired BRS predicts the CV mortality in a population-based sample of middle-aged subjects. The present study is a part of the Oulu Project Elucidating Risk of Atherosclerosis study, where middle-aged hypertensive and age- and gender-matched control subjects were randomly selected. Along with clinical and laboratory assessments, BRS was measured from the blood pressure overshoot of Valsalva maneuver in 559 subjects (age 51 ± 6 years; 300 men). The causes of death (n = 72) were registered during a follow-up of up to 19 years. CV death (n = 23) was defined as the primary end point. CV death was predicted by smoking status, alcohol consumption, high-sensitivity C-reactive protein, use of diuretics, waist circumference, and fasting glucose. Among all measured risk factors, impaired Valsalva BRS (<3 ms/mm Hg) was the most potent predictor of CV death (hazard ratio 9.1, 95% confidence interval 3.8 to 21.7, p <0.001) and remained so after adjustments for the other significant predictors (hazard ratio 5.3, 95% confidence interval 2.1 to 13.3, p <0.001). In conclusion, impaired Valsalva BRS is a potent and independent predictor of CV death in a population-based sample of middle-aged subjects without history of major CV complications and may have important clinical implications in early risk stratification.