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

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

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.

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.

Early Growth Patterns and Cardiac Structure and Function at Midlife: Northern Finland 1966 Birth Cohort Study.

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 (ß) or OR with 95% CIs for 1 SD increase in early growth variable. RESULTS: Earlier adiposity rebound was associated with increased LV mass index (ß = -4.10 g/m2 (-6.9, -1.3); P = .004) and LV end-diastolic volume index (ß = -2.36 mL/m2 (-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 (ß = 2.33 g/m2 [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 (ß = 1.47 mL/m2; [0.51, 2.4], ß = 1.28 mL/m2 [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.

Biomarkers as predictors of sudden cardiac death in coronary artery disease patients with preserved left ventricular function (ARTEMIS study).

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.

Effect of Changes in Physical Activity on Risk for Cardiac Death in Patients With Coronary Artery Disease.

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.

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

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

Lifelong Physical Activity and Cardiovascular Autonomic Function in Midlife.

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

Usefulness of Highly Sensitive Troponin as a Predictor of Short-Term Outcome in Patients With Diabetes Mellitus and Stable Coronary Artery Disease (from the ARTEMIS Study).

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.

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

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

Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (ß = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (ß = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (ß = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement.

Peak exercise capacity prediction from a submaximal exercise test in coronary artery disease patients.

The purpose of this study was to determine whether a rating of perceived exertion scale (RPE) obtained during submaximal exercise could be used to predict peak exercise capacity (METpeak) in coronary artery disease (CAD) patients. Angiographically documented CAD patients (n = 124, 87% on ß blockade) completed a symptom-limited peak exercise test on a bicycle ergometer, reporting RPE values at every second load on a scale of 6-20. Regression analysis was used to develop equations for predicting METpeak. We found that submaximal METs at a workload of 60/75 W (for women and men, respectively) and the corresponding RPE (METs/RPE ratio) was the most powerful predictor of METpeak (r = 0.67, p < 0.0001). The final model included the submaximal METs/RPE ratio, body mass index (BMI), sex, resting heart rate, smoking history, age, and use of a ß blockade (r = 0.86, p < 0.0001, SEE 0.98 METs). These data suggest that RPE at submaximal exercise intensity is related to METpeak in CAD patients. The model based on easily measured variables at rest and during "warm-up" exercise can reasonably predict absolute METpeak in patients with CAD.

Heart rate variability in sciatica patients referred to spine surgery: a case control study.

BACKGROUND: A chronic pain condition may result in altered autonomic nervous system regulation in various patient populations. We evaluated whether autonomic regulation differs between sciatica patients referred to spine surgery and age-matched healthy controls analyzed with heart rate variability techniques (HRV). METHODS: HRV of patients (n = 201) and healthy controls (n = 138) were measured in standing conditions (5 min). High frequency (HF) power as an index of cardiac vagal modulation and the low-to-high-frequency (LF/HF) ratio and short-term fractal scaling exponent α1 as indices of sympathovagal balance were analyzed. Pain intensity was assessed on a Visual Analog Scale (VAS) and perceived disability with Oswestry Disability Index. RESULTS: The Oswestry and VAS scores were higher in the patients than in the controls (p < 0.0001 for both). HF power was markedly lower for the patients compared to the controls (p < 0.0001). The LF/HF ratio and α1 were higher in the patients than in the controls (p < 0.01 for both). After adjusting for sex, smoking, BMI, and leisure-time physical activity, HF power (p = 0.011) and α1 (p = 0.012) still differed between the groups. Among the patients, HF power was slightly associated with the duration of chronic pain (r = -.232, p = 0.003). CONCLUSIONS: Sciatica patients referred to spine surgery had altered cardiac autonomic regulation expressed as decreased vagal activity and an increased sympathovagal balance toward sympathetic dominance when compared with age-matched healthy controls.

Leisure time emotional excitement increases endothelin-1 and interleukin-6 in cardiac patients.

OBJECTIVES. Emotional excitement may trigger serious cardiovascular (CV) events. Our objective was to compare the changes in potential surrogate markers of CV events in patients with coronary artery disease (CAD) during emotional excitement and exercise. DESIGN. Fifty-three enthusiastic ice-hockey spectators with stable CAD attended the Finnish national ice-hockey play-off matches and a maximal bicycle exercise. Plasma catecholamines, endothelin-1, interleukin-6, and markers of platelet activation and blood coagulation were determined before and during the match and before and after the exercise. RESULTS. Plasma endothelin-1 (2.82 ± 0.21 vs. 2.94 ± 0.25 pg/mL, p < 0.0001), noradrenaline (4.38 ± 1.79 vs. 4.77 ± 1.75 nmol/L, p = 0.009) and interleukin-6 (2.04 ± 1.98 vs. 2.90 ± 2.41 pg/mL, p < 0.0001) increased during the match, but markers of platelet activation and coagulation remained unchanged. Endothelin-1 did not change during exercise (2.73 ± 0.17 vs. 2.72 ± 0.19 pg/mL, p = 0.593) but noradrenaline (2.70 ± 1.08 vs.10.6 ± 5.5 nmol/L), adrenaline (0.23 ± 0.13 vs. 0.52 ± 0.37 nmol/L), interleukin-6 (1.77 ± 1.59 vs. 2.43 ± 1.78 pg/mL) and markers of platelet activation and blood coagulation increased significantly (p < 0.0001 for all). CONCLUSIONS. The responses of surrogate markers of acute CV events to emotional excitement and physical exercise are partly different. Emotional excitement causes concomitant increases in markers reflecting vulnerability to atherosclerotic plaque complications while physical exercise causes more prominent changes in markers of coagulation.

Coronary angioplasty in drug eluting stent era for the treatment of unprotected left main stenosis compared to coronary artery bypass grafting.

BACKGROUND: Improved outcomes of percutaneous coronary interventions (PCI) with drug-eluting stents (DES) have resulted in their expanded use for left main coronary artery (LMCA) stenosis. AIM: We compared outcomes of patients undergoing PCI for unprotected LMCA stenosis and patients treated by coronary artery bypass grafting (CABG). METHOD: Between January 2005 and January 2007, 6705 patients were studied with coronary angiography in northern Finland. All subjects treated with revascularization of LMCA stenosis (n = 287) were included and followed up for a mean of 12+6 months. RESULTS: From 287 patients, 238 underwent CABG, and 49 had PCI with DES. The incidence of 1-year mortality was 4% among the PCI-treated and 11% among CABG-treated patients (P = 0.136). After the first month, mortality among PCI-or CABG-treated patients did not differ statistically significantly (2% versus 7%, P = 0.133). The most significant independent predictor of mortality was reduced left ventricular systolic function (hazard ratio 14.9, 95% CI 5.5-40.0, P < 0.001). CONCLUSIONS: PCI with DES for selected LMCA disease patients results in short- and midterm outcomes comparable to results of CABG in general. PCI is a viable therapeutic option in selected patients with LMCA stenosis.