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.

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.

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).

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.

Human Adult Astrocyte Extracellular Vesicle Transcriptomics Study Identifies Specific RNAs Which Are Preferentially Secreted as EV Luminal Cargo.

Astrocytes are central nervous system (CNS)-restricted glial cells involved in synaptic function and CNS blood flow regulation. Astrocyte extracellular vesicles (EVs) participate in neuronal regulation. EVs carry RNAs, either surface-bound or luminal, which can be transferred to recipient cells. We characterized the secreted EVs and RNA cargo of human astrocytes derived from an adult brain. EVs were isolated by serial centrifugation and characterized with nanoparticle tracking analysis (NTA), Exoview, and immuno-transmission electron microscopy (TEM). RNA from cells, EVs, and proteinase K/RNase-treated EVs was analyzed by miRNA-seq. Human adult astrocyte EVs ranged in sizes from 50 to 200 nm, with CD81 as the main tetraspanin marker and larger EVs positive for integrin ß1. Comparison of the RNA between the cells and EVs identified RNA preferentially secreted in the EVs. In the case of miRNAs, enrichment analysis of their mRNA targets indicates that they are good candidates for mediating EV effects on recipient cells. The most abundant cellular miRNAs were also abundant in EVs, and the majority of their mRNA targets were found to be downregulated in mRNA-seq data, but the enrichment analysis lacked neuronal specificity. Proteinase K/RNase treatment of EV-enriched preparations identified RNAs secreted independently of EVs. Comparing the distribution of cellular and secreted RNA identifies the RNAs involved in intercellular communication via EVs.

Compositional association of 24-h movement behavior with incident major adverse cardiac events and all-cause mortality.

Cardiovascular disease (CVD) causes a high disease burden. Physical activity (PA) reduces CVD morbidity and mortality. We aimed to determine the relationship between the composition of moderate-to-vigorous PA (MVPA), light PA (LPA), sedentary behavior (SB), and sleep during midlife to the incidence of major adverse cardiac events (MACE) and all-cause mortality at a 7-year follow-up. The study population consisted of Northern Finland Birth Cohort 1966 members who participated in the 46-year follow-up in 2012 and were free of MACE (N = 4147). Time spent in MVPA, LPA, and SB was determined from accelerometer data. Sleep time was self-reported. Hospital visits and deaths were obtained from national registers. Participants were followed until December 31, 2019, or first MACE occurrence (acute myocardial infarction, unstable angina pectoris, stroke, hospitalization due to heart failure, or death due to CVD), death from another cause, or censoring. Cox proportional hazards model was used to estimate hazard ratios of MACE incidence and all-cause mortality. Isotemporal time reallocations were used to demonstrate the dose-response association between time spent in behaviors and outcome. The 24-h time composition was significantly associated with incident MACE and all-cause mortality. More time in MVPA relative to other behaviors was associated with a lower risk of events. Isotemporal time reallocations indicated that the greatest risk reduction occurred when MVPA replaced sleep. Higher MVPA associates with a reduced risk of incident MACE and all-cause mortality after accounting for the 24-h movement composition and confounders. Regular engagement in MVPA should be encouraged in midlife.

Carotid and femoral bruits as cardiovascular risk indicators in a middle-aged Finnish population: A 20-year prospective study.

BACKGROUND: Effective treatment and prevention of cardiovascular (CV) diseases requires reliable methods of assessing individual CV event risk. Although standardized risk calculators like Systematic Coronary Risk Evaluation (SCORE) are sufficient in most instances, sometimes more specific clinical examination is needed to determine the most optimal intervention and its intensity. AIM: To study whether carotid and femoral bruits provide prognostic information on CV events, CV mortality and all-cause mortality beyond traditional CV risk factors. METHODS: 1045 subjects (49.8% men), aged 51.3 ± 5.97 years were clinically examined in the beginning of 1990's. The subjects were followed for over 20 years and data on CV events and causes of deaths was collected. RESULTS: During the follow-up period, 241 (23.1%) of the subjects died and 82 (34.6%) of the deaths were of CV origin. Carotid bruits were a significant risk factor for CV deaths only if subjects with previous CV events were included. After adjusting for age, sex, systolic blood pressure, smoking, diabetes, LDL cholesterol, coronary artery disease and stroke, carotid bruits posed a hazard ratio (HR) (95% confidence interval) of 4.15 (2.39-8.52) p<0.001 for CV deaths. After excluding subjects with previous CV events (after which n = 941) neither carotid nor femoral bruits were statistically associated with CV events or all-cause mortality. Adding carotid or femoral bruits in the baseline risk model with traditional CV risk factors did not improve C-statistic, reclassification, or discrimination of the subjects. CONCLUSIONS: Carotid and femoral bruits do not provide clinically useful information in a pure primary prevention setting. Carotid bruits might be useful in evaluating the overall CV risk in a population where recurrent CV events may occur.

ECG T-Wave Morphologic Variations Predict Ventricular Arrhythmic Risk in Low- and Moderate-Risk Populations.

Background Early identification of individuals at risk of sudden cardiac death (SCD) remains a major challenge. The ECG is a simple, common test, with potential for large-scale application. We developed and tested the predictive value of a novel index quantifying T-wave morphologic variations with respect to a normal reference (TMV), which only requires one beat and a single-lead ECG. Methods and Results We obtained reference T-wave morphologies from 23 962 participants in the UK Biobank study. With Cox models, we determined the association between TMV and life-threatening ventricular arrhythmia in an independent data set from UK Biobank study without a history of cardiovascular events (N=51 794; median follow-up of 122 months) and SCD in patients with coronary artery disease from ARTEMIS (N=1872; median follow-up of 60 months). In UK Biobank study, 220 (0.4%) individuals developed life-threatening ventricular arrhythmias. TMV was significantly associated with life-threatening ventricular arrhythmias (hazard ratio [HR] of 1.13 per SD increase [95% CI, 1.03-1.24]; P=0.009). In ARTEMIS, 34 (1.8%) individuals reached the primary end point. Patients with TMV ≥5 had an HR for SCD of 2.86 (95% CI, 1.40-5.84; P=0.004) with respect to those with TMV <5, independently from QRS duration, corrected QT interval, and left ventricular ejection fraction. TMV was not significantly associated with death from a cause other than SCD. Conclusions TMV identifies individuals at life-threatening ventricular arrhythmia and SCD risk using a single-beat single-lead ECG, enabling inexpensive, quick, and safe risk assessment in large populations.

Association of atrial depolarization variability and cardiac autonomic regulation with sudden cardiac death in coronary artery disease.

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.

MiR-185-5p regulates the development of myocardial fibrosis.

BACKGROUND: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis. METHODS AND RESULTS: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-ß1 and collagen I. CONCLUSIONS: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.

Cardiovascular responses to dynamic and static upper-body exercise in a cold environment in coronary artery disease patients.

PURPOSE: Upper-body exercise performed in a cold environment may increase cardiovascular strain, which could be detrimental to patients with coronary artery disease (CAD). This study compared cardiovascular responses of CAD patients during graded upper-body dynamic and static exercise in cold and neutral environments. METHODS: 20 patients with stable CAD performed 30 min of progressive dynamic (light, moderate, and heavy rating of perceived exertion) and static (10, 15, 20, 25 and 30% of maximal voluntary contraction) upper body exercise in cold (- 15 °C) and neutral (+ 22 °C) environments. Heart rate (HR), blood pressure (BP) and electrocardiographic (ECG) responses were recorded and rate pressure product (RPP) calculated. RESULTS: Dynamic-graded upper-body exercise in the cold increased HR by 2.3-4.8% (p = 0.002-0.040), MAP by 3.9-5.9% (p = 0.038-0.454) and RPP by 18.1-24.4% (p = 0.002-0.020) when compared to the neutral environment. Static graded upper-body exercise in the cold resulted in higher MAP (6.3-9.1%; p = 0.000-0.014), lower HR (4.1-7.2%; p = 0.009-0.033), but unaltered RPP compared to a neutral environment. Heavy dynamic exercise resulted in ST depression that was not related to temperature. Otherwise, ECG was largely unaltered during exercise in either thermal condition. CONCLUSIONS: Dynamic- and static-graded upper-body exercise in the cold involves higher cardiovascular strain compared with a neutral environment among patients with stable CAD. However, no marked changes in electric cardiac function were observed. The results support the use of upper-body exercise in the cold in patients with stable CAD. TRIAL REGISTRATION: Clinical trial registration NCT02855905 August 2016.

Prognostic value of heart rate variability in patients with coronary artery disease in the current treatment era.

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.

Abdominal aorta plaques are better in predicting future cardiovascular events compared to carotid intima-media thickness: A 20-year prospective study.

BACKGROUND AND AIMS: Both carotid intima-media thickness (IMT) and arterial plaques have been shown to predict future CV events. Since there are no previous studies on the subject, our objective was to compare carotid IMT and the length of plaques in abdominal-pelvic main arteries in CV risk assessment in a prospective study setting with a follow-up of over 20 years. METHODS: A total of 1007 patients (50% men), aged 51 ± 6.0 years, participated in the current study. Carotid IMT and the summarized plaque length (SUM) from abdominal aorta to common femoral arteries were ultrasonographically assessed. Patients were followed-up a median (1st-3rd quartile) of 22.5 (17.5-23.2) years for CV events. RESULTS: SUM significantly predicted CV events (HR per every 10 mm increase: 1.035, 95% CI: 1.027-1.044, p < 0.001). Those in the highest SUM tertile had over 3-fold risk for CV event (HR: 3.392, 95% CI: 2.427-4.741, p < 0.001) when compared to those in the lowest tertile. SUM significantly predicted CV events even after adjusting for age, sex, hypertension, diabetes, smoking (pack-years), LDL cholesterol and IMT. Adding SUM to the established model improved C-index (95% CI) from 0.706 (0.674-0.738) to 0.718 (0.688-0.747) as well as both discrimination (p < 0.001) and reclassification (p < 0.001) of the patients. In contrast, IMT predicted cardiovascular events only in univariate analysis and it did not improve discrimination or reclassification of the patients. CONCLUSIONS: In light of our findings, SUM is a superior indicator and clinical tool for evaluating the overall CV risk compared to carotid IMT.

Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims.

The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.

Accumulation patterns of sedentary time and breaks and their association with cardiometabolic health markers in adults.

Breaking up sedentary time with physical activity (PA) could modify the detrimental cardiometabolic health effects of sedentary time. Our aim was to identify profiles according to distinct accumulation patterns of sedentary time and breaks in adults, and to investigate how these profiles are associated with cardiometabolic outcomes. Participants (n = 4439) of the Northern Finland Birth Cohort 1966 at age 46 years wore a hip-worn accelerometer for 7 consecutive days during waking hours. Uninterrupted ≥1-min sedentary bouts were identified, and non-sedentary bouts in between two consecutive sedentary bouts were considered as sedentary breaks. K-means clustering was performed with 65 variables characterizing how sedentary time was accumulated and interrupted. Linear regression was used to determine the association of accumulation patterns with cardiometabolic health markers. Four distinct groups were formed as follows: "Couch potatoes" (n = 1222), "Prolonged sitters" (n = 1179), "Shortened sitters" (n = 1529), and "Breakers" (n = 509). Couch potatoes had the highest level of sedentariness and the shortest sedentary breaks. Prolonged sitters, accumulating sedentary time in bouts of ≥15-30 min, had no differences in cardiometabolic outcomes compared with Couch potatoes. Shortened sitters accumulated sedentary time in bouts lasting <15 min and performed more light-intensity PA in their sedentary breaks, and Breakers performed more light-intensity and moderate-to-vigorous PA. These latter two profiles had lower levels of adiposity, blood lipids, and insulin sensitivity, compared with Couch potatoes (1.1-25.0% lower values depending on the cardiometabolic health outcome, group, and adjustments for potential confounders). Avoiding uninterrupted sedentary time with any active behavior from light-intensity upwards could be beneficial for cardiometabolic health in adults.

Resistin is a risk factor for all-cause mortality in elderly Finnish population: A prospective study in the OPERA cohort.

OBJECTIVE: Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people. METHODS: The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline. RESULTS: After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64-5.56, p<0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577-0.734), p<0.001 and an optimal cutoff value of 12.88 ng/ml. CONCLUSIONS: Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors.

Temporal variability of T-wave morphology and risk of sudden cardiac death in patients with coronary artery disease.

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.

Central aortic hemodynamics following acute lower and upper-body exercise in a cold environment among patients with coronary artery disease.

Exercise is beneficial to cardiovascular health, evidenced by reduced post-exercise central aortic blood pressure (BP) and wave reflection. We assessed if post-exercise central hemodynamics are modified due to an altered thermal state related to exercise in the cold in patients with coronary artery disease (CAD). CAD patients (n = 11) performed moderate-intensity lower-body exercise (walking at 65-70% of HRmax) and rested in neutral (+ 22 °C) and cold (- 15 °C) conditions. In another protocol, CAD patients (n = 15) performed static (five 1.5 min work cycles, 10-30% of maximal voluntary contraction) and dynamic (three 5 min workloads, 56-80% of HRmax) upper-body exercise at the same temperatures. Both datasets consisted of four 30-min exposures administered in random order. Central aortic BP and augmentation index (AI) were noninvasively assessed via pulse wave analyses prior to and 25 min after these interventions. Lower-body dynamic exercise decreased post-exercise central systolic BP (6-10 mmHg, p < 0.001) and AI (1-6%, p < 0.001) both after cold and neutral and conditions. Dynamic upper-body exercise lowered central systolic BP (2-4 mmHg, p < 0.001) after exposure to both temperatures. In contrast, static upper-body exercise increased central systolic BP after exposure to cold (7 ± 6 mmHg, p < 0.001). Acute dynamic lower and upper-body exercise mainly lowers post-exercise central BP in CAD patients irrespective of the environmental temperature. In contrast, central systolic BP was elevated after static exercise in cold. CAD patients likely benefit from year-round dynamic exercise, but hemodynamic responses following static exercise in a cold environment should be examined further.Clinical trials.gov: NCT02855905 04/08/2016.