Search

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 (mVO 2 ) 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 mVO 2 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 (mVO 2 , 0.054 ± 0.010 vs. 0.038 ± 0.012 mLO 2 /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., (© 2024 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Smartwatches and home-based blood pressure (BP) devices have permitted easy use of heart rate variability (HRV) and BP to identify the recovery status of users after acute exercise training. The reproducibility of HRV and BP after exercise in healthy young participants is not well known. Eighteen participants (age 27 ± 6 years, female n = 8) performed test and retest aerobic exercises (cycling, 30 min, 60% of peak workload, W) and a control session in randomized order. RMSSD, high and low-frequency power of RR intervals, and BP were measured at rest and 30-60 min after interventions. The relative reproducibility was assessed by the intraclass correlation coefficient (ICC) and 95% confidence interval (95% CI). The absolute reproducibility was evaluated using the coefficient of variation (CV%). HRV indices revealed moderate-to-excellent reproducibility at rest (ICC 0.81-0.86; 95% CI 0.53-0.95) but not after exercise (ICC -0.06 to 0.60; 95% CI -1.85 to 0.85). Systolic BP had a good-to-excellent reproducibility before (ICC 0.93; 95% CI 0.81-0.98, CV% 4.2) and after exercise (ICC 0.93; 95% CI 0.81-0.97, CV% 4.2). The reproducibility of HRV indices is poor after exercise in young participants. However, the reproducibility of BP is excellent at rest and after aerobic exercise., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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 χ 2 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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hautala, Shavazipour, Afsar, Tulppo and Miettinen.)

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 ms 2 and from 5.3 ± 0.8 to 5.2 ± 0.7 ms 2 , 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)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saarikoski, Roiha, Kiviniemi, Cerdán-De-las-Heras, Perkiömäki, Kaikkonen and Tulppo.)

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., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 [β, -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.

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., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

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 (R 2 = 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.

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.

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)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pikkarainen, Valtonen, Hintsala, Kiviniemi, Crandall, Perkiömäki, Hautala, Tulppo, Jaakkola and Ikäheimo.)

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.

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., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

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., (© 2023 Heart Rhythm Society.)

Aims: To evaluate the relationship between spatial heterogeneity of electrocardiographic repolarization and spatial heterogeneity of atrial depolarization with arrhythmic substrate represented by left ventricular fibrosis., Methods and Results: We assessed the associations of T- and P-wave morphology parameters analysed from the standard 12-lead electrocardiograms with left ventricular fibrosis in 378 victims of unexpected sudden cardiac death (SCD) who underwent medico-legal autopsy. Based on autopsy findings, the SCD victims were categorized into four different groups according to different stages of severity of left ventricular fibrosis (substantial fibrosis, moderate patchy fibrosis, scattered mild fibrosis, no fibrosis). T-wave and P-wave area dispersion (TWAd: 0.0841 ± 0.496, 0.170 ± 0.492, 0.302 ± 404, 0.296 ± 0.476, P = 0.008; PWAd: 0.574 ± 0.384, 0.561 ± 0.367, 0.654 ± 0.281, 0.717 ± 0.257, P = 0.011, respectively; low values abnormal), non-dipolar components of T-wave and P-wave morphology (T&#95;NonDipolarABS: 0.0496 ± 0.0377, 0.0571 ± 0.0487, 0.0432 ± 0.0476, 0.0380 ± 0.0377, P = 0.027; P&#95;NonDipolarABS: 0.0132 ± 0.0164, 0.0130 ± 0.0135, 0.0092 ± 0.0117, 0.0069 ± 0.00472, P = 0.005, respectively, high values abnormal), T-wave morphology dispersion (TMD: 45.9 ± 28.3, 40.5 ± 25.8, 35.5 ± 24.9, 33.0 ± 24.6, P = 0.030, respectively, high values abnormal), and P-wave heterogeneity (PWH: 20.0 ± 9.44, 19.7 ± 8.87, 17.9 ± 9.78, 15.4 ± 4.60, P = 0.019, respectively, high values abnormal) differed significantly between the groups with different stages of left ventricular fibrosis. After adjustment with heart weight, T&#95;NonDipolarABS [standardized β (sβ) = 0.131, P = 0.014], PWAd (sβ = -0.161, P = 0.003), P&#95;NonDipolarABS (sβ = 0.174, P = 0.001), and PWH (sβ = 0.128, P = 0.015) retained independent association, and TWAd (sβ = -0.091, P = 0.074) and TMD (sβ = 0.097, P = 0.063) tended to retain their association with the degree of myocardial fibrosis., Conclusion: Our findings suggest that abnormal values of T- and P-wave morphology are associated with arrhythmic substrate represented by ventricular fibrosis partly explaining the mechanism behind their prognostic significance., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate the prognostic significance of the temporal variability of P-wave morphology, specifically in relation to cardiac autonomic regulation., Methods and Results: We analyzed the standard deviation of P-wave residuum (PWRSD) from five consecutive beats of the standard 12-lead ECG in 1236 patients with angiographically verified coronary artery disease (CAD). We evaluated the prognostic value of PWRSD, of PWRSD and PWR in relation to the 24 h standard deviation of normal-to-normal intervals (PWRSD/SDNN and PWR/SDNN). After 8.7 ± 2.2 years of follow-up on average, 43 patients (3.5%) experienced sudden cardiac death (SCD) or were resuscitated from sudden cardiac arrest (SCA), 34 (2.8%) succumbed to non-sudden cardiac death (NSCD) and 113 (9.1%) to non-cardiac death (NCD). In the Cox regression analysis, PWRSD (≥0.002727) had a significant univariate (uv) [hazard ratio (HR): 4.27, 95% confidence interval (CI): 2.26-8.08, P = 0.000008] and multivariate (mv) (HR: 2.58, 95% CI: 1.31-5.08, P = 0.006) association with SCD/SCA but not with NSCD (uv P = 0.76, mv P = 0.33) or NCD (uv P = 0.57, mv P = 0.66). All the studied P-morphology parameters retained a significant association with the risk of SCD/SCA after relevant adjustment (mv P-values from 0.00003 to <0.05) but not with NSCD or NCD. When dichotomized PWRSD, PWR, PWRSD/SDNN, and PWR/SDNN were added to the clinical risk model for SCD/SCD, the C-index increased from 0.799 to 0.834 and integrated discrimination index and net reclassification index improved significantly (P < 0.001)., Conclusion: Variability of P-morphology representing temporo-spatial heterogeneity of atrial depolarization, specifically when combined with cardiac autonomic regulation, independently predicts the risk of SCD in patients with CAD., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Coronary artery disease (CAD) mortality has declined substantially over the past decades thanks to advancing medical and interventional/surgical treatments; therefore, the prognostic value of the heart rate variability in CAD in the current treatment era is not well established. We evaluated the prognostic significance of baseline heart rate variability in 1,757 ARTEMIS study patients with angiographically verified CAD. During an average follow-up time of 8.7 ± 2.2 years, a total of 285 (16.2%) patients died. Of the patients, 63 (3.6%) suffered sudden cardiac death or were resuscitated from sudden cardiac arrest (SCD/SCA), 60 (3.4%) experienced non-sudden cardiac death (NSCD), and death attributable to non-cardiac causes (NCD) occurred in 162 (9.2%) patients. For every 10 ms decrease in standard deviation of normal to normal intervals the risk for SCD/SCA, NSCD and NCD increased significantly: HR 1.153 (95% CI 1.075-1.236, p<0.001), HR 1.187 (95% CI 1.102-1.278, p<0.001) and HR 1.080 (95% CI 1.037-1.125, p<0.001), respectively. The natural logarithm of the low-frequency component of the power spectrum and the short-term scaling exponent of the detrended fluctuation analysis also had significant association with all modes of death (p<0.001). After relevant adjustment, standard deviation of normal-to-normal intervals retained its association with NSCD and NCD (p<0.01), the natural logarithm of the low-frequency component of the power spectrum with all modes of death (p from <0.05 to <0.01), and the short-term scaling exponent of the detrended fluctuation analysis with SCD/SCA (p<0.05) and NCD (p<0.001). In conclusion, impairment of many measures of heart rate variability predicts mortality but is not associated with any specific mode of death in patients with stable CAD during the current treatment era, limiting the clinical applicability of heart rate variability to targeting therapy., Competing Interests: The authors have declared that no competing interests exist.

Background: The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarization and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood., Methods: The standard deviation of T-wave morphology dispersion (TMD-SD), of QRST angle (QRSTA-SD), and of T-wave area dispersion (TW-Ad-SD) were analyzed on beat-to-beat basis from 10 min period of the baseline electrocardiographic recording in ARTEMIS study patients with angiographically verified CAD., Results: After on average of 8.6 ± 2.3 years of follow-up, a total of 66 of the 1,678 present study subjects (3.9%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was most closely associated with the risk for SCD and was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.61 ± 2.83 vs. 2.64 ± 2.52, p = .008, respectively), but did not differ significantly between the patients who had experienced non-SCD (n = 71, 4.2%) and those who remained alive (3.20 ± 2.73 vs. 2.65 ± 2.53, p = .077, respectively) or between the patients who succumbed to non-cardiac death (n = 164, 9.8%) and those who stayed alive (2.64 ± 2.17 vs. 2.68 ± 2.58, p = .853). After adjustments with relevant clinical risk indicators of SCD/SCA, TMD-SD still predicted SCD/SCA (HR 1.107, 95% CIs 1.035-1.185, p = .003)., Conclusions: Temporal variability of electrocardiographic spatial heterogeneity of repolarization represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD., (© 2021 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Introduction: The prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization measured from standard 12-lead ECG is not well-understood., Methods: We measured the short-term variability of repolarization parameters, such as T-wave heterogeneity in leads V4-V6 (TWH) and QT interval (QT), from five consecutive beats of previously recorded standard 12-lead ECG in 200 victims of unexpected sudden cardiac death (SCD) confirmed to be due to complicated atherosclerotic coronary artery disease (CAD) in medico-legal autopsy and 200 age- and sex-matched controls with angiographically confirmed CAD. The short-term variability of repolarization heterogeneity was defined as the standard deviation (SD) of the measured repolarization parameters. All ECGs were in sinus rhythm, and no premature ventricular contractions were included in the measured segment., Results: TWH-SD and QT-SD were significantly higher in SCD victims than in subjects with CAD (6.9 ± 5.6 μV vs. 3.8 ± 2.6 μV, p = 1.8E-11; 8.3 ± 13.1 ms vs. 3.8 ± 7.1 ms, p = 0.00003, respectively). After adjusting in the multivariate clinical model with factors, such as diabetes, RR interval, and beta blocker medication, TWH-SD and QT-SD retained their significant power in discriminating between the victims of SCD and the patients with CAD ( p = 0.00003, p = 0.006, respectively). TWH-SD outperformed QT-SD in identifying the SCD victims among the study subjects (area under the curve in the receiver operating characteristics curve 0.730 vs. 0.679, respectively)., Conclusion: Increased short-term variability of repolarization heterogeneity measured from standard 12-lead ECG is associated with SCD., (Copyright © 2020 Hekkanen, Kenttä, Haukilahti, Rahola, Holmström, Vähätalo, Tulppo, Kiviniemi, Pakanen, Ukkola, Junttila, Huikuri and Perkiömäki.)

Objectives: To evaluate the influence of early growth patterns that have previously been associated with later cardiometabolic risk on cardiac left ventricular (LV) structure and function in midlife., Study Design: A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1155) at the age of 46 years. Body mass index (BMI) growth curves were modeled based on frequent anthropometric measurements in childhood. Age and BMI at adiposity peak (n = 482, mean age 9.0 months) and at adiposity rebound (n = 586, mean age 5.8 years) were determined. Results are reported as unstandardized beta (β) or OR with 95% CIs for 1 SD increase in early growth variable., Results: Earlier adiposity rebound was associated with increased LV mass index (β = -4.10 g/m 2 (-6.9, -1.3); P = .004) and LV end-diastolic volume index (β = -2.36 mL/m 2 (-3.9, -0.84); P = .002) as well as with eccentric LV hypertrophy (OR 0.54 [0.38, 0.77]; P = .001) in adulthood in males. BMI at adiposity rebound was directly associated with LV mass index (β = 2.33 g/m 2 [0.80, 3.9]; P = .003). Higher BMI at both adiposity peak and at adiposity rebound were associated with greater LV end-diastolic volume index (β = 1.47 mL/m 2 ; [0.51, 2.4], β = 1.28 mL/m 2 [0.41, 2.2], respectively) and also with eccentric LV hypertrophy (OR 1.41 [1.10, 1.82], OR 1.53 [1.23, 1.91], respectively) and LV concentric remodeling (OR 1.38 [1.02, 1.87], OR 1.40 [1.06, 1.83], respectively) in adulthood (P < .05 for all). These relationships were only partly mediated by adult BMI., Conclusions: Early growth patterns in infancy and childhood contribute to cardiac structure at midlife., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The association between leisure-time physical activity (LTPA) and the risk of sudden cardiac death (SCD) in coronary artery disease patients is not well known. We aim to assess whether there is an association between LTPA and the risk of SCD and non-SCD in patients with coronary artery disease., Methods: Patients with angiographically verified coronary artery disease (n=1946) underwent a clinical evaluation, including filling in an LTPA questionnaire and extensive risk profiling at the baseline. The patients were classified into 4 groups according to LTPA: (1) inactive; (2) irregularly active; (3) active, exercise regularly 2× to 3× weekly; (4) highly active, exercise regularly ≥4× weekly. Age, sex, body mass index, left ventricular ejection fraction, type 2 diabetes mellitus, history of myocardial infarction, Canadian Cardiovascular Society grading of angina pectoris class, and exercise capacity were used as covariates in the multivariate Cox regression analysis., Results: During follow-up (median 6.3 years), 52 SCDs and 49 non-SCDs occurred. Inactive patients had increased risk for SCD compared with active patients (hazard ratio, 2.45 [95% CI, 1.01-5.98]; P <0.05). A significant LTPA×Canadian Cardiovascular Society grading of angina pectoris class interaction was observed in SCD risk ( P =0.019 in highly active patients). LTPA was not associated with SCD in patients with Canadian Cardiovascular Society grading of angina pectoris class 1 (n=1107, 18 events). Among patients with Canadian Cardiovascular Society grading of angina pectoris class 2 or higher (n=839, 34 events), increased risk for SCD was encountered in highly active patients (hazard ratio, 7.46 [95% CI, 2.32-23.9]; P <0.001) and inactive patients (hazard ratio, 3.64 [95% CI, 1.16-11.5]; P <0.05) as compared to active patients. A linear association was observed between LTPA and non-SCD; those with high LTPA had the lowest risk for non-SCD., Conclusions: Inactive coronary artery disease patients had increased risk for SCD. In subgroup analysis among symptomatic patients, the risk of SCD was increased in highly active and inactive patients compared with active patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01426685.

Objective: To evaluate postexercise heart rate recovery (HRR) in adults born preterm., Study Design: We studied the association between preterm birth and postexercise HRR in 545 adults (267 women) at 23.3 years of age (range 19.9-26.3 years). One hundred three participants were born early preterm (<34 completed weeks), 178 late preterm (34-36), and 264 were full term (control group). HRR was calculated as change in heart rate (HR) 30 seconds and 60 seconds after cessation of submaximal step test and maximum HR slope during the first minute after., Results: Mean peak HR was 159.5 bpm in the early preterm (P = .16 with controls), 157.8 bpm in the late preterm (P = .56), and 157.0 bpm in the control group. Mean HRR 30 seconds after exercise was 3.2 bpm (95% CI 1.1-5.2) lower in the early preterm group and 2.1 bpm (0.3-3.8) lower in the late preterm group than the full term controls. Mean 60s HRR was 2.5 (-0.1 to 5.1) lower in the early preterm group and 2.8 bpm (0.6-4.9) lower in the late preterm group. Mean maximum slope after exercise was 0.10 beats/s (0.02-0.17) lower in the early preterm group and 0.06 beats/s (0.00-0.12) lower in the late preterm group., Conclusions: Our results suggest reduced HRR after exercise in adults born preterm, including those born late preterm. This suggests altered reactivation of the parasympathetic nervous system, which may contribute to cardiovascular risk among adults born preterm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To test the hypothesis that age and body mass index (BMI) at BMI peak during infancy and at BMI rebound in childhood are related to cardiovascular autonomic modulation in adulthood., Methods: At the age of 46 years, a sample (n = 5861) of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. Heart rate variability (HRV), baroreflex sensitivity (BRS) and low-frequency oscillations of systolic blood pressure (LF SBP ) were measured during sympathetic stimulus by standing. BMI at various ages was calculated from frequent anthropometric measurements collected from child welfare clinical records. BRS and LF SBP were available for 1243 participants with BMI peak data and 1524 participants with BMI rebound data, and HRV for 2137 participants with BMI peak data and 2688 participants with BMI rebound data., Results: Age at BMI rebound had a significant inverse association with LF SBP (beta = -0.071, p = 0.006) after all adjustments (p < 0.001) and was also directly associated with BRS (beta = 0.082, p = 0.001) independently of birth and maternal factors (p = 0.023). BMI at BMI peak and at BMI rebound was inversely associated with high-frequency component of HRV (HF) (beta = -0.045, p = 0.036 for BMI at peak; beta = -0.043, p = 0.024 for BMI at rebound) and directly associated with the ratio of low- and high-frequency components of HRV (LF/HF ratio) (beta = 0.084, p = < 0.001 for BMI at peak; beta = 0.069, p < 0.001 for BMI at rebound). These associations remained significant after all adjustments (p < 0.05 for all)., Conclusions: This novel study shows that younger age at BMI rebound and higher BMI at BMI peak and at BMI rebound are associated with higher levels in markers suggestive of augmented sympathetic and reduced vagal cardiovascular modulation in midlife.

Objective: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes., Research Design and Methods: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes ( n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status ( n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points., Results: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death ( P = 0.069), 32% lower adjusted risk for all-cause mortality ( P = 0.076), and 36% lower adjusted risk for MACE ( P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality ( P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status., Conclusions: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status., (© 2019 by the American Diabetes Association.)

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3-minutes sitting, 3-minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate-to-vigorous PA (MVPA) for 2 weeks by wrist-worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized β = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (β = 0.10, P = 0.001), while MVPA was not (β = 0.04 for RRi 30:15 ratio and β = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (β = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2-fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Exaggerated sympathetic cardiovascular (CV) reactivity to stress associates with elevated risk for clinical and preclinical end points of CV disease. It would be useful to identify these individuals, preferably from feasible measurements commonly used in health care. Our study examined the association between home blood pressure (BP) variability and cardiac workload response to whole-body cold exposure., Methods: Seventy-five men (55-65 years, 46 hypertensive) measured BP at home twice in the morning and evening for a week. We computed systolic home BP variability as SD of daily means and divided the subjects into groups demonstrating either high or low BP variability. They were exposed to whole-body cold exposure (-10 °C, wind 3 m/second, 15 minutes, winter clothes, standing). BP and heart rate were measured at 3-minute intervals during, and 15 minutes before and after the exposure. Rate-pressure product (RPP) was calculated to represent cardiac workload., Results: Subjects with high systolic home BP variability demonstrated a greater RPP increase in cold conditions compared to those with low BP variability [mean change from baseline (95% CI): 1,850 (1,450 to 2,250) bpm × mm Hg vs. 930 (610, 1,250) bpm × mm Hg, P < 0.01]. This was related to the augmented systolic BP change [31(28, 35) mm Hg vs. 23(20, 26) mm Hg, P < 0.01]. Home BP variability correlated with cold-related RPP (rS = 0.34, P = 0.003) and systolic BP (rS = 0.38, P < 0.001) responses., Conclusions: Moderate whole-body cold exposure increased BP and cardiac workload more among those with higher systolic home BP variability, independently of home BP level. Elevated home BP variability may indicate augmented sympathetically mediated vascular reactivity for environmental stressors., Public Trials Registry Number: Trial Number NCT02007031., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: To investigate prognostic significance of post-exercise recovery of rate-pressure product (RPP) in patients with stable coronary artery disease (CAD) and type 2 diabetes (T2D)., Methods: Patients with angiographically documented CAD and T2D (n = 697) underwent symptom-limited bicycle exercise test. Exercise capacity (EC), heart rate, blood pressure and RPP responses to peak exercise and recovery (2' and 5' after cessation of exercise) were analyzed. Cardiac death was the primary and sudden cardiac death (SCD) secondary endpoint., Results: During a median follow-up of 76 months, 49 cardiac deaths (7.0%) and 28 SCDs (4.0%) were observed. The recovery of RPP at 5' was the strongest univariate predictor of cardiac death (hazard ratio [HR]: 2.55 per SD decrease, 95%CI: 1.82-3.58, p < 0.001) and SCD (HR: 2.34, 95%CI: 1.51-3.62, p < 0.001). In multivariate analysis, it remained significantly associated to cardiac death and SCD without (HR: 1.66, 95%CI: 1.14-2.41, p < 0.01 and HR: 1.75, 95%CI: 1.08-2.85, p < 0.05, respectively) and with additional adjustment for EC and peak RPP (HR: 1.45, 95%CI: 1.09-1.92, p < 0.05 and HR: 1.52, 95%CI: 1.01-2.27, p < 0.05, respectively)., Conclusions: The recovery of RPP after exercise is a potent predictor of cardiac death in patients with CAD and T2D. It provides significant prognostic information beyond EC and peak RPP., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Previous studies have documented that day-to-day variability of heart rate (HR) has prognostic significance for cardiovascular (CV) events in general population. It is unknown how HR dynamics variate before imminent CV event in patients with coronary artery disease (CAD). Our aim was to study day-to-day variation in HR dynamics before the occurrence of CV event in patients with initially stable CAD. Methods: Forty-four patients with angiographically documented CAD from ARTEMIS study measured R-R intervals on a weekly basis at home for 2 years. Home measurements were performed in controlled conditions (3 min at supine and sitting) 1-2 times per week. Eleven patients had a CV event (7 acute coronary syndromes, 1 cardiac death, 2 new onset of arrhythmia needing hospitalization and 1 stroke), which occurred 11 ± 7 months after enrolment. Mean R-R interval was analyzed prospectively from the home measurements. For the patients with new CV event, average, and standard deviation (SD) of the mean R-R interval over 8 weeks preceding the CV event were calculated. For the patients without new CV event, corresponding period was determined by the median follow-up at the occurrence of new CV event. Results: There were no differences in the mean R-R interval analyzed over 8 weeks between the patients with and without new CV event. The variability of mean R-R interval over 8 weeks was greater in the patients with new CV event compared to the patients without new CV event at the supine (95 ± 34 vs. 59 ± 26 ms, p < 0.001) and sitting positions (92 ± 28 vs. 62 ± 24 ms, p < 0.001). Conclusion: Day-to-day variability of mean R-R interval is greater before the new CV event in CAD patients suggesting to a more unstable cardiac autonomic regulation preceding these events.

Aims: Biomarkers have shown promising results in risk assessment of cardiovascular events. Their role in predicting the risk of sudden cardiac death (SCD) is not well established. We tested the performance of several biomarkers in risk assessment for SCD in patients with coronary artery disease (CAD) and preserved left ventricular function., Methods and Results: The study population consisted of 1,946 CAD patients (68% male; mean age 66.9±8.6 yrs; type 2 diabetes (T2D) 43%) enrolled in the ARTEMIS study. The study subjects underwent examinations with echocardiography and measurement of several biomarkers. The primary endpoint of the study was SCD. During the mean follow up of 76±20 months 50 patients experienced SCD. Elevated high sensitive CRP (hs-CRP, p = 0.001), soluble ST2 (sST2, p<0.001), B-type natriuretic peptide (BNP, p<0.001), and highly sensitive TroponinT (hs-TnT, p<0.001) predicted the occurrence of SCD in univariate analysis. Using the optimal cutoff points, elevated sST2 (≥27.45ng/mL; hazard ratio [HR] 2.7; 95%CI 1.4-5.1, p = 0.003) and hs-TnT (≥15 ng/mL; HR 2.9; 95% CI 1.5-5.6, p = 0.002) were the strongest predictors of SCD followed by hs-CRP (HR 2.4; 95% CI 1.3-4.4, p = 0.004) and BNP (HR 1.9; 95% CI 1.0-3.7, p = 0.046) in adjusted analysis. Combination of elevated hs-TnT and sST2 resulted in adjusted HR of 6.4 (95% CI 2.6-15.5, p<0.001)., Conclusion: Elevated sST2 and hs-TnT predict the occurrence of SCD among patients with CAD and preserved left ventricular function. The association between sST2, hs-TnT and SCD may be explained by an ongoing myocardial apoptosis followed by fibrosis leading to vulnerability to malignant arrhythmias., Competing Interests: The authors have declared that no competing interests exist.

The association between the mode of death and depression in patients with stable coronary artery disease (CAD) is far from clear. We investigated the association between depressive symptoms and the mode of death including all-cause mortality, noncardiac death, sudden cardiac death (SCD), and non-SCD in stable CAD patients. Patients with angiographically documented CAD (n = 1,928) underwent a clinical examination including screening for depression symptoms with the Depression Scale (DEPS) and extensive risk profiling at the baseline. The patients were divided into quartiles based on their DEPS score. The patients entered the follow-up (median 6.3 years) during which 49 SCDs (2.5%) and 48 non-SCDs (2.5%) occurred. The incidence of SCD was 1.1% (5 events), 2.0% (9 events), 2.6% (14 events), and 4.4% (21 events) from the lowest to the highest quartile of DEPS. The patients in the highest quartile of DEPS had a fourfold elevated univariate risk (95% confidence interval 1.5 to 10.5; p = 0.006), and after adjustment for traditional risk factors, a 3.2-fold elevated multivariate risk (95% confidence interval 1.2 to 8.9, p = 0.025) for SCD compared with patients in the lowest quartile. DEPS was not associated with non-SCD or noncardiac deaths. Depressive symptoms are associated with an increased risk of SCD independently of clinical risk factors in patients with CAD. The results highlight the importance of screening for depression and emphasize the need for additional interventions to alleviate the depressive symptoms in these patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Leisure-time physical activity (LTPA) is associated with longevity in patients with coronary artery disease (CAD). However, less is known about prognostic significance of longitudinally assessed LTPA in patients with stable CAD. The present study assessed the relationship between changes in LTPA and cardiac mortality in patients with CAD. Patients with angiographically documented CAD (n = 1,746) underwent clinical examination and echocardiography at the baseline. Lifestyle factors, including LTPA (inactive, irregularly active, active, highly active), were surveyed at baseline and after 2 years' follow-up. Thereafter, the patients entered the follow-up (median: 4.5 years; first to third quartile: 3.4 to 5.8 years) during which cardiac deaths were registered (n = 68, 3.9%). The patients who remained inactive (n = 114, 18 events, 16%) and became inactive (n = 228, 18 events, 8%) had 7.6- (95% confidence interval [CI] 4.2 to 13.6) and 3.7-fold (95% CI 2.1 to 6.7) univariate risk for cardiac death compared with those who remained at least irregularly active (n = 1,351, 30 events, 2%), respectively. After adjustment for age, gender, body mass index, diabetes, previous myocardial infarction, left ventricular ejection fraction, angina pectoris grading, cardiovascular event during initial 2-year follow-up, smoking and alcohol consumption, the patients who remained inactive and became inactive still had 4.9- (95% CI 2.4 to 9.8, p <0.001) and 2.4-fold (95% CI 1.3 to 4.5, p <0.01) risk for cardiac death, respectively, compared with patients remaining at least irregularly active. In conclusion, LTPA has important prognostic value for cardiac death in patients with stable CAD. Even minor changes in LTPA over 2 years were related to the subsequent risk for cardiac death., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Although low cardiorespiratory fitness (CRF), physical inactivity, and obesity are associated with impaired autonomic function, they are also extensively interrelated. The present study aimed to assess the extent to which they contribute to autonomic function independently of each other., Methods: At the age of 46 yr, 1383 men and 1761 women without cardiorespiratory diseases and diabetes underwent assessments of vagally mediated heart rate (HR) variability (root mean square of successive differences in R-R interval (rMMSD)), peak HR during a submaximal step test (CRF), and 60-s HR recovery (HRR). Moderate-to-vigorous physical activity (MVPA; ≥3.5 METs, 2 wk) was measured by wrist-worn accelerometer and body fat percentage (Fat%) by bioimpedance., Results: In men, CRF and Fat% were significantly associated with higher rMSSD (standardized β = 0.31 and -0.16) and HRR (β = 0.19 and -0.18), whereas higher MVPA was linked with higher HRR (β = 0.13) when including CRF, MVPA, and Fat% in the initial regression. After adjustments for other lifestyle and cardiometabolic factors, CRF remained significantly associated with rMMSD (β = 0.24) and HRR (β = 0.14), as did MVPA with HRR (β = 0.11). In women, CRF was associated with rMSSD (β = 0.23) and HRR (β = 0.15), and MVPA (β = 0.17) and Fat% (β = -0.07) with HRR, when CRF, MVPA, and Fat% were adjusted for each other. After further adjustments, CRF remained a significant determinant of rMSSD (β = 0.20) and HRR (β = 0.13), as did MVPA with HRR (β = 0.15). The final models explained 23% and 21% of variation in rMSSD and HRR in men, and 10% and 12% in women, respectively., Conclusions: CRF was a more important determinant of cardiac autonomic function than MVPA and body fat. Furthermore, MVPA but not body fat was independently associated with cardiac autonomic function in both men and women.

Health care decision-making requires evidence of the cost-effectiveness of medical therapies. We evaluated the cost-effectiveness of exercise-based cardiac rehabilitation (ECR) implemented according to guidelines. All the patients (n = 204) had experienced a recent acute coronary syndrome and were randomized to a 1-year ECR (n = 109) or usual care (UC) group (n = 95). The patients' health-related quality of life was followed using the 15D instrument and health care costs were collected from electronic health registries. The cost-effectiveness of ECR was estimated based on intervention and health care costs and quality-adjusted life years (QALYs) gained. The total average cost per patient was lower in ECR than in UC. The incremental cost was divided by the baseline-adjusted incremental QALYs (0.045), yielding an incremental cost-effectiveness ratio of -€24511/QALYs. A combined endpoint of mortality, recurrent coronary event, or hospitalization for a heart failure occurred for five patients in ECR and 16 patients in UC (HR 3.9, 95% CI 1.4-10.6, P = 0.004, relative risk reduction 73%, number needed to treat eight). ECR is a dominant treatment option and decreases the occurrence of adverse cardiac events. These results are useful for decision-making when planning optimal utilization of resources in Finnish health care., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55-65 years) who underwent a whole-body cold exposure (-10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg(2), compared with hypertensive group [0 (-13, 20) mmHg(2)]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension.

The aim of this study was to test the hypothesis that novel biomarkers may predict cardiac events in diabetic patients with stable coronary artery disease (CAD). Serum levels of highly sensitive troponin T (hs-TnT), B-type natriuretic peptide, highly sensitive C-reactive protein (hs-CRP), galectin-3, and soluble suppressor of tumorigenicity-2 (sST2) were analyzed in 1,137 patients with CAD and with type 2 diabetes, impaired glucose tolerance, or fasting glycaemia (diabetic group) and in 649 patients with normal glucose state. Cardiac death or hospitalization for congestive heart failure was the major end point during the follow-up of 2 years. Forty patients in the diabetic group (3.5%) and 9 patients in the nondiabetic group (1.4%) reached the primary end point. High hs-TnT level (≥14 ng/l) was the strongest predictor of the primary end point with hazard ratio of 24.5 (95% confidence interval 8.7 to 69.0; p <0.001) and remained so when adjusted for clinical variables, ejection fraction, renal, lipid, and glycemic status and other biomarkers (hazard ratio 9.9, 95% confidence interval 3.2 to 30.8; p <0.001). In the multivariate model, hs-CRP, B-type natriuretic peptide, and sST2 also predicted the primary end point in the diabetic group (p <0.01 for all). Only sST2 (p <0.001) and hs-CRP (p = 0.02) predicted the primary end point in nondiabetic group. The inclusion of hs-TnT in the model significantly improved discrimination (integrated discrimination improvement 0.050) and reclassification of the patients (net reclassification index 0.21). In conclusion, hs-TnT is a strong predictor of cardiac death or hospitalization for heart failure independently from traditional risk markers or other biomarkers in diabetic patients with stable CAD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 β 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We tested the hypothesis that baseline cardiac autonomic function and its acute response to all-out interval exercise explains individual fitness responses to high-intensity interval training (HIT). Healthy middle-aged sedentary men performed HIT (n=12, 4-6×30 s of all-out cycling efforts with 4-min recovery) or aerobic training (AET, n=9, 40-60 min at 60% of peak workload in exercise test [Loadpeak]), comprising 6 sessions within 2 weeks. Low (LF) and high frequency (HF) power of R-R interval oscillation were analyzed from data recorded at supine and standing position (5+5 min) every morning during the intervention. A significant training effect (p< 0.001), without a training*group interaction, was observed in Loadpeak and peak oxygen consumption (VO2peak). Pre-training supine LF/HF ratio, an estimate of sympathovagal balance, correlated with training outcome in Loadpeak (Spearman's rho [rs]=-0.74, p=0.006) and VO2peak (rs=- 0.59, p=0.042) in the HIT but not the AET group. Also, the mean change in the standing LF/HF ratio in the morning after an acute HIT exercise during the 1(st) week of intervention correlated with training response in Loadpeak (rs=- 0.68, p=0.014) and VO2peak (rs=-0.60, p=0.039) with HIT but not with AET. In conclusion, pre-training cardiac sympathovagal balance and its initial alterations in response to acute HIT exercise were related to fitness responses to short-term HIT., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Increased risk of arrhythmic events occurs at certain times during the circadian cycle with the highest risk being in the second and fourth quarter of the day. Exercise improves treatment outcome in individuals with cardiovascular disease. How different exercise protocols affect the circadian rhythm and the associated decrease in adverse cardiovascular risk over the circadian cycle has not been shown., Methods: Fifty sedentary male participants were randomized into an 8-week high volume and moderate volume training and a control group. Heart rate was recorded using Polar Electronics and investigated with Cosinor analysis and by Poincaré plot derived features of SD1, SD2 and the complex correlation measure (CCM) at 1-h intervals over the 24-h period., Results: Moderate exercise significantly increased vagal modulation and the temporal dynamics of the heart rate in the second quarter of the circadian cycle (p = 0.004 and p = 0.007 respectively). High volume exercise had a similar effect on vagal output (p = 0.003) and temporal dynamics (p = 0.003). Cosinor analysis confirms that the circadian heart rate displays a shift in the acrophage following moderate and high volume exercise from before waking (1st quarter) to after waking (2nd quarter of day)., Conclusions: Our results suggest that exercise shifts vagal influence and increases temporal dynamics of the heart rate to the 2nd quarter of the day and suggest that this may be the underlying physiological change leading to a decrease in adverse arrhythmic events during this otherwise high-risk period.

Background and Aims: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized., Methods and Results: The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis., Conclusions: Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)