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.

Physical Activity, Fitness, and Cardiac Autonomic Function among Adults Born Postterm.

Recent studies have suggested that adverse outcomes of postterm birth (≥42 completed weeks of gestation), including increased cardiometabolic risk factors, impaired glucose metabolism, and obesity, may extend into adulthood. We studied interconnected determinants of cardiovascular health, including physical activity (based on accelerometry for two weeks), muscular strength (handgrip strength), cardiorespiratory fitness (4-min step test), and cardiac autonomic function (heart rate recovery, heart rate variability, and baroreflex sensitivity) among 46-year-old adults from the Northern Finland Birth Cohort (NFBC) born postterm (n = 805) and at term (n = 2,645). Adults born postterm undertook vigorous-intensity physical activity 2.0 min/day (95% CI 0.4, 3.7) less than term-born adults when adjusted for sex, age, and maternal- and pregnancy-related covariates in multiple linear regression. Postterm birth was associated with reduced cardiorespiratory fitness based on a higher peak heart rate (2.1 bpm, 95% CI 0.9, 3.4) and slower heart rate recovery 30 s after the step test (-0.7 bpm, 95% CI -1.3, -0.1). Postterm birth was associated with lower vigorous-intensity physical activity and cardiorespiratory fitness and slower heart rate recovery in middle age. Our findings reinforce previous suggestions that postterm birth should be included as a perinatal risk factor for adult cardiometabolic disease.

Chronotype and metabolic syndrome in midlife: findings from the Northern Finland Birth Cohort 1966.

Evening chronotype is known to be associated with various chronic diseases and cardiovascular risk factors. Metabolic syndrome is a group of conditions that together raise the risk of coronary heart disease, diabetes, stroke, and other serious health problems. Only a few studies have been published on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. The aim of this study was to evaluate the association between chronotype and metabolic syndrome at population level by using unselected Northern Finland Birth cohort 1966 (NFBC1966) database. The study population consists of participants with NFBC66 (n = 5,113, 57% female) at the age of 46 yr old. Chronotype was determined with shortened Morningness-Eveningness Questionnaires and expressed as morning (44%), intermediate (44%), and evening types (12%). Metabolic syndrome was determined according to the definition of International Diabetes Federation. One-way ANOVA, Kruskal-Walli's test, and χ2 tests were used to compare the chronotype groups, followed by logistic regression analysis (adjusted with alcohol consumption, smoking, marital status, level of education, and leisure-time physical activity). In women, the prevalence of metabolic syndrome was statistically significantly higher in the evening type group: 23, 24, and 34% for morning, intermediate, and evening groups, respectively (P < 0.001). In logistic regression analysis, evening chronotype was associated with higher risk of having metabolic syndrome (OR 1.5; CI 95% 1.2 to 2.0). In this population-based birth cohort study, the evening chronotype was independently associated with higher prevalence of metabolic syndrome in women.NEW & NOTEWORTHY Only a few studies have been conducted on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. In this population-based cohort study of 5,113 participants, the evening chronotype associated with metabolic syndrome in women when there was no such association in men. The result supports a previous South Korean population study of 1,620 participants, in which the association was also found in women, but not in men.

Prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization analyzed from a 5-minute resting electrocardiogram in coronary artery disease.

BACKGROUND: Data on the prognostic significance of temporal variability of spatial heterogeneity of electrocardiographic repolarization in coronary artery disease (CAD) are limited. OBJECTIVE: The purpose of this study was to evaluate the prognostic value of temporal variability of T-wave morphology analyzed from a 5-minute resting electrocardiogram in CAD. METHODS: The standard deviation (SD) of T-wave morphology dispersion (TMD-SD) and the SD of total cosine R-to-T were analyzed on a beat-to-beat basis from a 5-minute period of the standard resting 12-lead electrocardiogram obtained before the clinical stress test in 1702 patients with angiographically verified CAD and well-preserved left ventricular function. RESULTS: During an average of 8.7 ± 2.2 years of follow-up, 60 patients experienced sudden cardiac death/arrest (SCD/SCA) (3.5%), 69 patients nonsudden cardiac death (NSCD) (4.1%), and 161 patients noncardiac death (9.5%). TMD-SD was significantly higher in patients who experienced SCD/SCA than in other patients (1.72 ± 2.00 vs 1.12 ± 1.75; P = .01) and higher in patients who succumbed to NSCD than in other patients (1.57 ± 1.74 vs 1.12 ± 1.76; P = .04), but it did not differ significantly between patients who experienced noncardiac death and those without such an event (1.16 ± 1.42 vs 1.14 ± 1.79; P = .86). In the Cox multivariable hazards model, TMD-SD retained its significant association with the risk of SCD/SCA (hazard ratio 1.119; 95% confidence interval 1.015-1.233; P = .024) but not with the risk of NSCD (hazard ratio 1.089; 95% confidence interval 0.983-1.206; P = .103). CONCLUSION: TMD-SD is independently associated with the long-term risk of SCD/SCA in patients with CAD.

Reproducibility and sex differences in muscle oxygenation during brachial artery occlusion in healthy participants.

SIGNIFICANCE: Near-infrared spectroscopy (NIRS) measurement is a widely used technique to measure muscle oxygenation. A knowledge of the reproducibility of NIRS measurements is essential for the correct interpretation of data. AIM: Our aim was to test the reproducibility and sex differences of NIRS measurements during brachial artery occlusion in healthy participants. APPROACH: An NIRS device was used to measure muscle oxygenation and microvascular function during a 5 min brachial occlusion. Muscle oxygen consumption (mVO2) and tissue saturation index (TSI%) were used. The occlusion test was performed three times on separate days for males (n = 13, 28 ± 8 years) and females (n = 13, 29 ± 7 years). RESULTS: During the occlusion phase, the reproducibility of mVO2 was excellent (intraclass correlation; ICC = 0.90). During the reperfusion phase, the maximal change in TSI% revealed the best reproducibility (ICC = 0.77). There were no sex differences in reproducibility. Male participants had higher muscle oxygenation during occlusion (mVO2, 0.054 ± 0.010 vs. 0.038 ± 0.012 mLO2/min/100 g, p = 0.001, male and female, respectively). There were no sex differences during the reperfusion phase. CONCLUSION: The reproducibility of NIRS to measure muscle oxygenation and microvascular function during circulation occlusion and reperfusion is good to excellent. Muscle oxygen capacity measured during occlusion is higher in males compared to females, and there are no sex differences in microvascular function during the reperfusion phase.

Autonomic Nervous System Activity and Dental Anxiety in the Northern Finland Birth Cohort (NFBC1966) Population.

Autonomic nervous system (ANS) activity may be associated with dental anxiety; however, no studies exist on the topic. The aim of this study was to assess if ANS activity and dental anxiety are associated. Data were collected as part of a Northern Finland Birth Cohort Study, NFBC1966, at the age of 46 years with eligible data on 1905 participants. Dental anxiety was measured using the Modified Dental Anxiety Scale (MDAS) categorized as follows: 19-25 = high, 10-18 = moderate, 5-9 = no to low dental anxiety. Heart rate variability (HRV) data were collected using an HR monitor and a standard lead-II electrocardiogram (ECG). Baroreflex sensitivity (BRS) was calculated from continuous ECG and blood pressure signals. Participants were categorized into three groups as follows: Low = the lowest 20th percentile, Mid = medium 21-79th percentile, and High = the highest 20th percentile according to their ANS variables. The associations between the MDAS and ANS activity parameters were evaluated using unordered multinomial logit models adjusted for comorbidities, ß-blockers, BMI, smoking, and education. High heart rate, reduced HRV, low cardiac vagal modulation, and poor BRS were associated with moderate dental anxiety, and high cardiac vagal modulation and good BRS were associated with no to low dental anxiety. Poorer ANS activity might predispose some to dental anxiety, and better ANS activity might protect from dental anxiety.

Effect of Aerobic Exercise and Time-Restricted Feeding on Metabolic Markers and Circadian Rhythm in Mice Fed with the High-Fat Diet.

SCOPE: Diet and exercise are significant players in obesity and metabolic diseases. Time-restricted feeding (tRF) has been shown to improve metabolic responses by regulating circadian clocks but whether it acts synergically with exercise remains unknown. It is hypothesized that forced exercise alone or combined with tRF alleviates obesity and its metabolic complications. METHODS AND RESULTS: Male C57bl6 mice are fed with high-fat or a control diet for 12 weeks either ad libitum or tRF for 10 h during their active period. High-fat diet (HFD)-fed mice are divided into exercise (treadmill for 1 h at 12 m min-1 alternate days for 9 weeks and 16 m min-1 daily for the following 3 weeks) and non-exercise groups. tRF and tRF-Ex significantly decreased body weight, food intake, and plasma lipids, and improved glucose tolerance. However, exercise reduced only body weight and plasma lipids. tRF and tRF-Ex significantly downregulated Fasn, Hmgcr, and Srebp1c, while exercise only Hmgcr. HFD feeding disrupted clock genes, but exercise, tRF, and tRF-Ex coordinated the circadian clock genes Bmal1, Per2, and Rev-Erbα in the liver, adipose tissue, and skeletal muscles. CONCLUSION: HFD feeding disrupted clock genes in the peripheral organs while exercise, tRF, and their combination restored clock genes and improved metabolic consequences induced by high-fat diet feeding.

Liver X Receptor Agonist 4ß-Hydroxycholesterol as a Prognostic Factor in Coronary Artery Disease.

BACKGROUND: Regardless of progress in treatment of coronary artery disease (CAD), there is still a significant residual risk of death in patients with CAD, highlighting the need for additional risk stratification markers. Our previous study provided evidence for a novel blood pressure-regulating mechanism involving 4ß-hydroxycholesterol (4ßHC), an agonist for liver X receptors, as a hypotensive factor. The aim was to determine the role of 4ßHC as a prognostic factor in CAD. METHODS AND RESULTS: The ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) cohort consists of 1946 patients with CAD. Men and women were analyzed separately in quartiles according to plasma 4ßHC. Basic characteristics, medications, ECG, and echocardiography parameters as well as mortality rate were analyzed. At baseline, subjects with a beneficial cardiovascular profile, as assessed with traditional markers such as body mass index, exercise capacity, prevalence of diabetes, and use of antihypertensives, had the highest plasma 4ßHC concentrations. However, in men, high plasma 4ßHC was associated with all-cause death, cardiac death, and especially sudden cardiac death (SCD) in a median follow-up of 8.8 years. Univariate and comprehensively adjusted hazard ratios for SCD in the highest quartile were 3.76 (95% CI, 1.6-8.7; P=0.002) and 4.18 (95% CI, 1.5-11.4; P=0.005), respectively. In contrast, the association of cardiac death and SCD in women showed the lowest risk in the highest 4ßHC quartile. CONCLUSIONS: High plasma 4ßHC concentration was associated with death and especially SCD in men, while an inverse association was detected in women. Our results suggest 4ßHC as a novel sex-specific risk marker of cardiac death and especially SCD in chronic CAD. REGISTRATION INFORMATION: clinicaltrials.gov. Identifier NCT01426685.

Adherence to exercise after an acute coronary syndrome: a 6-month randomized controlled trial.

Introduction: Exercise training with well-known health benefits is a key element in the self-management of coronary artery disease (CAD). Although current guidelines for patients with CAD recommend daily exercise training, most of the patients do not follow the guidelines. We tested the hypothesis that an exercise training program guided by a novel technology used at home will improve adherence to exercise training. Methods: One to three weeks after percutaneous coronary intervention (PCI), acute coronary syndrome patients (n = 50) were randomized into traditional (age 65 ± 8 years) and novel technology-guided (age 60 ± 8 years) exercise rehabilitation groups. The novel technology included a tablet computer with a virtual autonomous physiotherapy agent (VAPA group) for every patient at home; it was used to guide exercise training time, volume, and intensity. Traditional rehabilitation was performed by exercise training prescriptions, phone calls, and diaries (control group). The duration of the rehabilitation program was 6 months for both groups. Exercise capacity and 24-h heart rate variability were measured at baseline and at the end of the program. Adherence to exercise was measured over 6 months as the percentage of realized training. Results: None of the patients dropped out from the VAPA group, while three patients dropped out from the control group. Adherence to exercise was higher in the VAPA group than in the control group for resistance training (141% ± 56% vs. 50% ± 20%, p < 0.0001), and there were no differences between the groups for aerobic training (144% ± 45% vs. 119% ± 65%, p = 0.22). Exercise capacity increased in both the groups (time p < 0.001, time × group interaction p = ns). High-frequency power of R-R intervals (lnHF) increased in the VAPA group but remained unchanged in the control group (natural logarithm of lnHF power from 5.5 ± 0.7 to 5.8 ± 0.9 ms2 and from 5.3 ± 0.8 to 5.2 ± 0.7 ms2, respectively, time × group interaction p = 0.014). Conclusion: Compared with the use of traditional methods, the use of novel technology at home results in better adherence to exercise, particularly in resistance training, in acute coronary syndrome patients. Second, the VAPA group showed improved cardiac vagal regulation, documented by increased vagally mediated R-R interval fluctuation, compared with the traditional training group (ClinicalTrials.gov identifier: NCT03704025).

Lifestyle and Cardiac Structure and Function in Healthy Midlife Population.

The association between lifestyle and cardiac structure and function measures, such as global longitudinal strain and diastolic function in a healthy midlife general population, is not well known. A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1,155) at the age of 46. All antihypertensive medication users (n = 164), patients with diabetes (n = 70), subjects with any cardiac diseases (n = 24), and subjects with echocardiography abnormalities (n = 21) were excluded. Moderate to vigorous physical activity (MVPA) was recorded with a wrist-worn accelerometer over 14 days and categorized into high, moderate, and low MVPA groups. Similarly, alcohol consumption was categorized as low, moderate, and high-dose users of alcohol and smoking as nonsmokers, former, and current smokers. The total number of healthy subjects included in the study was 715 (44% males). Left ventricular mass index and left atrial end-systolic volume index were significantly higher in the high MVPA group compared with the low MVPA group (adjusted main effect p = 0.002 and p <0.001, respectively). Cardiac function did not differ among the physical activity groups. High alcohol consumption was associated with impaired global longitudinal strain and diastolic function (adjusted main effect p = 0.002 and p = 0.004, respectively) but not with any cardiac structure variables. Smoking was not associated with cardiac structure or function. In healthy middle-aged adults, MVPA was independently associated with structural changes in the heart but not with cardiac function. High alcohol consumption was associated with impaired modern cardiac function measures but not with cardiac structure.

Physical activity, residential greenness, and cardiac autonomic function.

PURPOSE: This population-based study examines the associations between physical activity (PA), residential environmental greenness, and cardiac health measured by resting short-term heart rate variability (HRV). METHODS: Residential greenness of a birth cohort sample (n = 5433) at 46 years was measured with normalized difference vegetation index (NDVI) by fixing a 1 km buffer around each participant's home. Daily light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and the combination of both (MVPA) were measured using a wrist-worn accelerometer for 14 days. Resting HRV was measured with a heart rate monitor, and generalized additive modeling (GAM) was used to examine the association between PA, NDVI, and resting HRV. RESULTS: In nongreen areas, men had less PA at all intensity levels compared to men in green areas. Women had more LPA and total PA and less MPA, MVPA, and VPA in green residential areas compared to nongreen areas. In green residential areas, men had more MPA, MVPA, and VPA than women, whereas women had more LPA than men. GAM showed positive linear associations between LPA, MVPA and HRV in all models. CONCLUSIONS: Higher LPA and MVPA were significantly associated with increased HRV, irrespective of residential greenness. Greenness was positively associated with PA at all intensity levels in men, whereas in women, a positive association was found for LPA and total PA. A positive relationship of PA with resting HRV and greenness with PA was found. Residential greenness for promoting PA and heart health in adults should be considered in city planning.

Preeclampsia-exposed children's heart rate variability 8-12 yr after index pregnancy: FINNCARE study.

Preeclampsia is related with elevated systolic blood pressure (SBP) in children. We studied if preeclampsia-exposed (PE) children develop alterations in heart rate variability (HRV) and if this is reflected in their blood pressure (BP), as well as overall associations with body size and composition, gestational and perinatal factors. We examined 182 PE (46 early-onset PE) and 85 unexposed (non-PE) children 8-12 yr after preeclampsia exposure. HRV monitoring was performed 5 min in supine followed by 5 min in standing position and compared with office, 24-h ambulatory, and central BPs in relation to body anthropometrics and composition, gestational, and perinatal data. There were no major differences in HRV between PE and non-PE children. HRV in supine position was strongly associated with office and ambulatory heart rates (HRs), and HR was independently associated with office BPs. However, HRV was not related with office or 24-h SBP and PP, nor with elevated SBP in PE compared with non-PE children [adjusted mean differences for office and 24-h SBP 4.8 (P < 0.001) and 2.5 mmHg (P = 0.049), respectively]. In supine position, high-frequency (HF) power [ß, -0.04 (95% CI -0.06 to -0.01)], root mean square of successive differences in R-R intervals (rMSSD) [-0.015 (-0.028 to -0.002)], and the ratio of low-frequency (LF) to HF power [0.03 (0.01-0.04)] were independently associated with child fat mass. LF and HF power and rMSSD displayed independent inverse associations with child age. There were no significant associations between child HRV and gestational and perinatal factors. During prepuberty, the HRV in children with PE is similar to that in non-PE children. Elevated SBP following preeclampsia exposure is not related with HRV. Child adiposity could be related to decreased cardiac vagal tone.NEW & NOTEWORTHY Heart rate variability in preadolescent children exposed to preeclampsia in utero is no different from age-matched controls. Preeclampsia-exposed children's elevated SBP is not related to alterations in heart rate variability, which is a noninvasive measure of the modulation of heart rate by autonomic tone. However, childhood adiposity might be coupled with diminished cardiac vagal tone.

Preterm-Born Young Women Have Weaker Hand Grip Strength Compared to Their Full-Term-Born Peers.

Prematurity has been linked to lower muscular fitness and increased morbidity across the human lifespan. Hand grip strength is widely used as a measure of muscle strength. Previous studies have shown inconsistent results regarding the role of vitamin D in hand grip strength. Here, we investigated hand grip strength and the effects of a yearlong vitamin D supplementation in healthy preterm-born young adults. We recruited 38 young adults born preterm at either ≤32 weeks' gestation or <34 weeks' gestation and weighing <1500 g, as well as 39 gender- and age-matched controls, for this study. Anthropometric measurements, hand grip strengths, and vitamin D concentrations were recorded. These investigations were repeated after a yearlong vitamin D supplementation intervention. There was a significant difference in the age- and gender-specific hand grip strength ranks between the preterm- and full-term-born young adults: 57.9% and 30.7%, respectively, were below average (p = 0.009). In the preterm-born group, the females had significantly lower hand grip strengths compared to their full-term-born peers, with a mean difference of -3.46 kg (95% CI: -6.68 to -0.247; p = 0.035). In a linear regression analysis, the preterm-born female adult height was negatively associated with hand grip strength (R2 = 0.24, F (1.43) = 13.61, p < 0.001). The vitamin D concentrations were increased after the supplementation period, with no association with hand grip strength. According to our results, preterm-born young females are at risk for lower muscle strength, independent of their current vitamin D status.

Metabolic patterns of sweat-extracellular vesicles during exercise and recovery states using clinical grade patches.

Background: Metabolite-based sensors are attractive and highly valued for monitoring physiological parameters during rest and/or during physical activities. Owing to their molecular composition consisting of nucleic acids, proteins, and metabolites, extracellular vesicles (EVs) have become acknowledged as a novel tool for disease diagnosis. However, the evidence for sweat related EVs delivering information of physical and recovery states remains to be addressed. Methods: Taking advantage of our recently published methodology allowing the enrichment and isolation of sweat EVs from clinical patches, we investigated the metabolic load of sweat EVs in healthy participants exposed to exercise test or recovery condition. -Ten healthy volunteers (-three females and -seven males) were recruited to participate in this study. During exercise test and recovery condition, clinical patches were attached to participants' skin, on their back. Following exercise test or recovery condition, the patches were carefully removed and proceed for sweat EVs isolation. To explore the metabolic composition of sweat EVs, a targeted global metabolomics profiling of 41 metabolites was performed. Results: Our results identified seventeen metabolites in sweat EVs. These are associated with amino acids, glutamate, glutathione, fatty acids, creatine, and glycolysis pathways. Furthermore, when comparing the metabolites' levels in sweat EVs isolated during exercise to the metabolite levels in sweat EVs collected after recovery, our findings revealed a distinct metabolic profiling of sweat EVs. Furthermore, the level of these metabolites, mainly myristate, may reflect an inverse correlation with blood glucose, heart rate, and respiratory rate levels. Conclusion: Our data demonstrated that sweat EVs can be purified using routinely used clinical patches during physical activity, setting the foundations for larger-scale clinical cohort work. Furthermore, the metabolites identified in sweat EVs also offer a realistic means to identify relevant sport performance biomarkers. This study thus provides proof-of-concept towards a novel methodology that will focus on the use of sweat EVs and their metabolic composition as a non-invasive approach for developing the next-generation of sport wearable sensors.

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

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).

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.

Lower hemoglobin levels associate with higher baroreflex sensitivity and heart rate variability.

The aim of this study was to cross-sectionally examine whether hemoglobin (Hb) levels within the normal variation associate with heart rate variability (HRV) measures and baroreflex sensitivity (BRS). The study population included 733 Finnish subjects of the OPERA cohort (aged 41-59 yr, 53% males, 51.7% treated for hypertension) of whom HRV was measured from a standardized 45-min period and whose Hb levels were within the Finnish reference intervals. The low Hb tertile (mean Hb, 135 g/L) had an overall healthier metabolic profile compared with the high Hb tertile (mean Hb, 152 g/L). BRS was higher in the low Hb tertile compared with the high Hb tertile (P < 0.05). R-R interval (RRi) and standard deviation (SD) of the RRi (SDNN)index were the longest in the low Hb tertile regardless of posture. Of the spectral components of HRV, HF power was the highest in the low Hb tertile regardless of posture (P < 0.05). In a stepwise logistic regression model, BRS associated negatively with Hb levels after adjusting for covariates (B = -0.160 [-0.285; -0.035]). Similar associations were observed for SDNNindex when lying down (B = -0.105 [-0.207; -0.003]) and walking (B = -0.154 [-0.224; -0.083]). For HF power negative associations with Hb levels were observed when lying down (B = -0.110 [-0.180; -0.040]), sitting (B = -0.150 [-0.221; -0.079]), and in total analysis (B = -0.124 [-0.196; -0.053]). Overall, lower Hb levels associated independently with healthier cardiac autonomic function.NEW & NOTEWORTHY Heart rate variability (HRV) and baroreflex sensitivity (BRS), which can be measured noninvasively, can predict cardiac and metabolic diseases. Our findings show that within normal variation subjects with lower hemoglobin (Hb) levels have an overall healthier HRV profile and increased cardiac parasympathetic activity in middle age, independent of age, sex, smoking status, and key metabolic covariates. These findings support our previous findings that Hb levels can be used in assessing long-term risks for cardiometabolic diseases.

Endothelin-1 is associated with mortality that can be attenuated with high intensity statin therapy in patients with stable coronary artery disease.

BACKGROUND: All coronary artery disease (CAD) patients do not benefit equally of secondary prevention. Individualized intensity of drug therapy is currently implemented in guidelines for CAD and diabetes. Novel biomarkers are needed to identify patient subgroups potentially benefitting from individual therapy. This study aimed to investigate endothelin-1 (ET-1) as a biomarker for increased risk of adverse events and to evaluate if medication could alleviate the risks in patients with high ET-1. METHODS: A prospective observational cohort study ARTEMIS included 1946 patients with angiographically documented CAD. Blood samples and baseline data were collected at enrollment and the patients were followed for 11 years. Multivariable Cox regression was used to assess the association between circulating ET-1 level and all-cause mortality, cardiovascular (CV) death, non-CV death and sudden cardiac death (SCD). RESULTS: Here we show an association of circulating ET-1 level with higher risk for all-cause mortality (HR: 2.06; 95% CI 1.5-2.83), CV death, non-CV death and SCD in patients with CAD. Importantly, high intensity statin therapy reduces the risk for all-cause mortality (adjusted HR: 0.05; 95% CI 0.01-0.38) and CV death (adjusted HR: 0.06; 95% CI 0.01-0.44) in patients with high ET-1, but not in patients with low ET-1. High intensity statin therapy does not associate with reduction of risk for non-CV death or SCD. CONCLUSIONS: Our data suggests a prognostic value for high circulating ET-1 in patients with stable CAD. High intensity statin therapy associates with reduction of risk for all-cause mortality and CV death in CAD patients with high ET-1.

Patients with coronary artery disease (CAD) ­ in which the blood vessels supplying the heart become blocked - need careful management to prevent adverse outcomes related to their disease, such as a heart attack or sudden cardiac death. Identification of markers in the blood to predict adverse outcomes would help to improve the care of patients with CAD. Here, we find that higher circulating levels of endothelin-1 (ET-1), a protein secreted normally to maintain blood pressure, associate with greater risk of death in CAD patients. Cholesterol-lowering statin therapy used at high intensity (high dosage) can counteract the increased risk of death observed in CAD patients with high ET-1. Therefore, circulating ET-1 level could be used as a marker to predict the risk of death in CAD patients, and an indication for high intensity statin therapy. Our findings could help clinicians to improve the management of patients with CAD.

The Influence of Oral Cannabidiol on 24-h Ambulatory Blood Pressure and Arterial Stiffness in Untreated Hypertension: A Double-Blind, Placebo-Controlled, Cross-Over Pilot Study.

INTRODUCTION: Studies reveal that cannabidiol may acutely reduce blood pressure and arterial stiffness in normotensive humans; however, it remains unknown if this holds true in patients with untreated hypertension. We aimed to extend these findings to examine the influence of the administration of cannabidiol on 24-h ambulatory blood pressure and arterial stiffness in hypertensive individuals. METHODS: Sixteen volunteers (eight females) with untreated hypertension (elevated blood pressure, stage 1, stage 2) were given oral cannabidiol (150 mg every 8 h) or placebo for 24 h in a randomised, placebo-controlled, double-blind, cross-over study. Measures of 24-h ambulatory blood pressure and electrocardiogram (ECG) monitoring and estimates of arterial stiffness and heart rate variability were obtained. Physical activity and sleep were also recorded. RESULTS: Although physical activity, sleep patterns and heart rate variability were comparable between groups, arterial stiffness (~ 0.7 m/s), systolic blood pressure (~ 5 mmHg), and mean arterial pressure (~ 3 mmHg) were all significantly (P < 0.05) lower over 24 h on cannabidiol when compared to the placebo. These reductions were generally larger during sleep. Oral cannabidiol was safe and well tolerated with no development of new sustained arrhythmias. CONCLUSIONS: Our findings indicate that acute dosing of cannabidiol over 24 h can lower blood pressure and arterial stiffness in individuals with untreated hypertension. The clinical implications and safety of longer-term cannabidiol usage in treated and untreated hypertension remains to be established.