Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

Variability of echocardiographic measures of left ventricular diastolic function. The HUNT study.

OBJECTIVE: Investigate variability related to image acquisition and reading process for echocardiographic measures of left ventricular (LV) diastolic function, and its influence on classification of LV diastolic dysfunction (LVDD). METHODS: Forty participants (19 women) mean age 62 (28-88) years underwent echocardiographic examinations twice by different echocardiographers and blinded analyses by four readers in a cross-sectional design. Measurements included quantification of two- (2D) and three-dimensional (3D) recordings of the left atrium (LA) (maximal) volume (LAVmax ) and spectral Doppler blood flow and tissue velocities for assessment of LV diastolic function. Variability and reproducibility measures were calculated using variance component analyses and Kappa statistics. RESULTS: Image acquisition influenced variability more than image reading (mean 24% and 4% of variance, respectively), but variability from image reading was especially important for 2D LAVmax (16% of variance) compared to 4% for 3D LAVmax , which was reflected in better agreement for 3D measures. The variability of measures used in classification of LVDD had clinical significance, and agreement across the four raters in classification using current recommendations was only fair (Kappa 0.42), but the agreement improved when using 3D LAVmax (Kappa 0.58). Agreement and reliability measures were reported for all measures. CONCLUSION: Performing a new image acquisition influenced variability more than a introducing a new image reader, but there were differences across the different measures. LAVmax by 3D is superior to 2D with respect to lower variability. The variability of diastolic measures influences the reliability of LVDD classification, and this should be taken into account in the everyday clinic.

Peak oxygen uptake and incident coronary heart disease in a healthy population: the HUNT Fitness Study.

AIMS: The majority of previous research on the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is based on indirect assessment of CRF in clinically referred predominantly male populations. Therefore, our aim was to examine the associations between VO2peak measured by the gold-standard method of cardiopulmonary exercise testing and fatal and non-fatal coronary heart disease (CHD) in a healthy and fit population. METHODS AND RESULTS: Data on VO2peak from 4527 adults (51% women) with no previous history of cardiovascular or lung disease, cancer, and hypertension or use of antihypertensive medications participating in a large population-based health-study (The HUNT3 Study), were linked to hospital registries and the cause of death registry. Average VO2peak was 36.0 mL/kg/min and 44.4 mL/kg/min among women and men, and 83.5% had low 10-year risk of CVD at baseline. Average follow-up was 8.8 years, and 147 participants reached the primary endpoint. Multi-adjusted Cox-regression showed 15% lower risk for the primary endpoint per one-MET (metabolic equivalent task) higher VO2peak [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.93], with similar results across sex. The highest quartile of VO2peak had 48% lower risk of event compared with the lowest quartile (multi-adjusted HR 0.52, 95% CI 0.33-0.82). Oxygen pulse and ventilatory equivalents of oxygen and carbon dioxide also showed significant predictive value for the primary endpoint. CONCLUSION: VO2peak was strongly and inversely associated with CHD across the whole fitness continuum in a low-risk population sample. Increasing VO2peak may have substantial benefits in reducing the burden of CHD.

Age-related decline in peak oxygen uptake: Cross-sectional vs. longitudinal findings. A review.

Cardiorespiratory fitness is established as an important prognostic factor for cardiovascular and general health. In clinical settings cardiorespiratory fitness is often measured by cardiopulmonary exercise testing determining the gold-standard peak oxygen uptake (VO2peak). Due to the considerable impact of age and sex on VO2peak, results from cardiopulmonary exercise testing are typically assessed in the context of age- and sex-specific reference values, and multiple studies have been conducted establishing reference materials by age and sex using cross-sectional designs. However, crossectional and longitudinal studies have shown somewhat conflicting results regarding age-related declines of VO2peak, with larger declines reported in longitudinal studies. In this brief review, we compare findings from crossectional and longitudinal studies on age-related trajectories in VO2peak to highlight differences in these estimates which should be acknowledged when clinicians interpret VO2peak measurements repeated over time.

Normalized Echocardiographic Values From Guideline-Directed Dedicated Views for Cardiac Dimensions and Left Ventricular Function.

BACKGROUND: Continuous technologic development and updated recommendations for image acquisitions creates a need to update the current normal reference ranges for echocardiography. The best method of indexing cardiac volumes is unknown. OBJECTIVES: The authors used 2- and 3-dimensional echocardiographic data from a large cohort of healthy individuals to provide updated normal reference data for dimensions and volumes of the cardiac chambers as well as central Doppler measurements. METHODS: In the fourth wave of the HUNT (Trøndelag Health) study in Norway 2,462 individuals underwent comprehensive echocardiography. Of these, 1,412 (55.8% women) were classified as normal and formed the basis for updated normal reference ranges. Volumetric measures were indexed to body surface area and height in powers of 1 to 3. RESULTS: Normal reference data for echocardiographic dimensions, volumes, and Doppler measurements were presented according to sex and age. Left ventricular ejection fraction had lower normal limits of 50.8% for women and 49.6% for men. According to sex-specific age groups, the upper normal limits for left atrial end-systolic volume indexed to body surface area ranged from 44 mL/m2 to 53 mL/m2, and the corresponding upper normal limit for right ventricular basal dimension ranged from 43 mm to 53 mm. Indexing to height raised to the power of 3 accounted for more of the variation between sexes than indexing to body surface area. CONCLUSIONS: The authors present updated normal reference values for a wide range of echocardiographic measures of both left- and right-side ventricular and atrial size and function from a large healthy population with a wide age-span. The higher upper normal limits for left atrial volume and right ventricular dimension highlight the importance of updating reference ranges accordingly following refinement of echocardiographic methods.

Cardiorespiratory fitness and the incidence of surgery for aortic valve stenosis-the HUNT study.

OBJECTIVES: Aortic valve stenosis (AVS) shares many risk factors with coronary disease, the latter being strongly and inversely associated with physical activity (PA) and cardiorespiratory fitness (CRF). However, the relationship between PA, CRF and AVS needs to be established. We explored whether PA habits and estimated CRF affect the risk of developing AVS demanding aortic valve replacement (AVR) and how these factors affect postoperative mortality. METHODS: Participants from the second and third waves of Trøndelag Health Study were cross-linked with a local heart surgery registry and the Norwegian Cause of Death Registry. Estimated CRF was calculated through a developed algorithm based on clinical and self-reported data. Fine-Gray competing risk analyses were used to investigate how PA habits and estimated CRF were associated with the risk of AVR across CRF quintiles, PA groups and per 1-metabolic equivalent task (MET) (3.5 ml/min/kg). RESULTS: In a study population of 57 214 participants, we found a 15% [95% confidence interval (CI) 1-27] reduced risk of AVR per 1-MET estimated CRF increment. Those in the highest CRF quintile had a 56% (95% CI 14-77) lower risk of surgery compared to the lowest quintile. Analyses on PA groups did not show significant results. Finally, we found a 37% (95% CI 17-53) lower risk of postoperative mortality per 1-MET increased estimated CRF. CONCLUSIONS: Our findings indicate a strong and inverse relationship between estimated CRF and incidence of AVR due to AVS. Higher estimated CRF was associated with lower mortality after surgery.

Effects of training adaption in endurance athletes with atrial fibrillation: protocol for a multicentre randomised controlled trial.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity. Trial registration number: NCT04991337. Study protocol version: 4.7 (Date 9 March 2023).

Indexing cardiac volumes for peak oxygen uptake to improve differentiation of physiological and pathological remodeling: from elite athletes to heart failure patients.

AIMS: Cardiovascular structures adapt to meet metabolic demands, but current methodology for indexing by body size does not accurately reflect such variations. Therefore, we aimed to investigate how left ventricular end-diastolic volume (LVEDV) and left atrial maximal volume (LAVmax) are associated with absolute (L/min) peak oxygen uptake (VO2peak) and fat-free mass (FFM) compared to body surface area (BSA). We subsequently assessed the impact of indexing by absolute VO2peak, FFM, and BSA to discriminate pathological from physiological remodeling. METHODS AND RESULTS: We used data from 1190 healthy adults to explore relationships for BSA, FFM, and absolute VO2peak with LVEDV and LAVmax by regression and correlation analyses. We then compared these indexing methods for classification to normalcy/pathology in 61 heart failure patients and 71 endurance athletes using the chi-squared and Fisher exact tests and the net reclassification and integrated discrimination indices. Absolute VO2peak correlated strongly with LVEDV, explaining 52% of variance vs. 32% for BSA and 44% for FFM. Indexing LVEDV for VO2peak improved discrimination between heart failure patients and athletes on top of indexing to BSA. Seventeen out of 18 athletes classified to pathology by BSA were reclassified to normalcy by VO2peak indexing (P < 0.001), while heart failure patients were reclassified to pathology (39-95%, P < 0.001). All indexing methods explained below 20% of the variance in LAVmax in univariate models. CONCLUSIONS: Indexing LVEDV to VO2peak improves the ability to differentiate physiological and pathological enlargement. The LVEDV to absolute VO2peak ratio may be a key index in diagnosing heart failure and evaluating the athlete's heart.

Cardiorespiratory fitness and the incidence of coronary surgery and postoperative mortality: the HUNT study.

OBJECTIVES: Low physical activity and cardiorespiratory fitness are known risk factors for coronary artery disease, but how they affect the risk of undergoing coronary artery bypass graft surgery is not established. We explored how physical activity and estimated cardiorespiratory fitness affect the risk of coronary surgery and postoperative outcome. METHODS: Participants with no history of coronary disease from the second wave of the Trøndelag Health Study (HUNT2) were cross-linked with the local heart surgery register and the Norwegian Cause of Death Registry. Cardiorespiratory fitness was estimated by a previously developed algorithm using clinical and self-reported information. Fine-Gray competing risk analyses were used to calculate the risk of undergoing isolated coronary surgery across physical activity groups and estimated cardiorespiratory fitness (mL/kg/min) as quintiles and per 1 metabolic equivalent of task (MET) (3.5 mL/kg/min). RESULTS: We included 45,491 participants. The mean population age was 46.0 [standard deviation (SD) 15.8] years, and the mean estimated fitness was 41.3 (SD 8.9) mL/kg/min. A total of 672 (1.5%) participants underwent coronary surgery during the follow-up period. The risk of undergoing isolated coronary surgery was 26% [95% confidence interval (CI) 3-44] lower for those classified as highly active compared to those classified as least active. Further, an 11% (95% CI 6-15) lower risk per 1-MET (3.5 mL/kg/min) of higher fitness. Finally, we observed a 15% (95% CI 5-23) lower mortality risk after surgery per 1-MET of higher fitness among those undergoing surgery. CONCLUSIONS: High levels of physical activity and high estimated fitness levels were inversely associated with the risk of developing coronary disease requiring surgery and overall mortality after surgery.

Age-related change in peak oxygen uptake and change of cardiovascular risk factors. The HUNT Study.

BACKGROUND: Large longitudinal studies on change in directly measured peak oxygen uptake (VO2peak) is lacking, and its significance for change of cardiovascular risk factors is uncertain. We aimed to assess ten-year change in VO2peak and the influence of leisure-time physical activity (LTPA), and the association between change in VO2peak and change in cardiovascular risk factors. METHODS AND RESULTS: A healthy general population sample had their VO2peak directly measured in two (n = 1431) surveys of the Nord-Trøndelag Health Study (HUNT3; 2006-2008 and HUNT4; 2017-19). Average ten-year decline in VO2peak was non-linear and progressed from 3% in the third to about 20% in the eight decade in life and was more pronounced in men. The fit linear mixed models including an additional 2,933 observations from subjects participating only in HUNT3 showed similar age-related decline. Self-reported adherence to LTPA recommendations was associated with better maintenance of VO2peak, with intensity seemingly more important than minutes of LTPA with higher age. Adjusted linear regression analyses showed that one mL/kg/min better maintenance of VO2peak was associated with favorable changes of individual cardiovascular risk factors (all p ≤ 0.002). Using logistic regression one mL/kg/min better maintenance of VO2peak was associated with lower adjusted odds ratio of hypertension (0.95 95% CI 0.92 to 0.98), dyslipidemia (0.92 95% CI 0.89 to 0.94), and metabolic syndrome (0.86 95% CI 0.83 to 0.90) at follow-up. CONCLUSIONS: Although VO2peak declines progressively with age, performing LTPA and especially high-intensity LTPA is associated with less decline. Maintaining VO2peak is associated with an improved cardiovascular risk profile.

Left Atrial Volume, Cardiorespiratory Fitness, and Diastolic Function in Healthy Individuals: The HUNT Study, Norway.

Background Left atrial (LA) size and cardiorespiratory fitness (CRF) are predictors of future cardiovascular events in high-risk populations. LA dilatation is a diagnostic criterion for left ventricular diastolic dysfunction. However, LA is dilated in endurance athletes with high CRF, but little is known about the association between CRF and LA size in healthy, free-living individuals. We hypothesized that in a healthy population, LA size was associated with CRF and leisure-time physical activity, but not with echocardiographic indexes of left ventricular diastolic dysfunction. Methods and Results In this cross-sectional study from HUNT (Nord-Trøndelag Health Study), 107 men and 138 women, aged 20 to 82 years, without hypertension, cardiovascular, pulmonary, or malignant disease participated. LA volume was assessed by echocardiography and indexed to body surface area LAVI (left atrial volume index). CRF was measured as peak oxygen uptake (VO2peak) using ergospirometry, and percent of age- and-sex-predicted VO2peak was calculated. Indexes of left ventricular diastolic dysfunction were assessed in accordance with latest recommendations. LAVI was >34 mL/m2 in 39% of participants, and LAVI was positively associated with VO2peak and percentage of age- and-sex-predicted VO2peak (ß [95% CI], 0.11 [0.06-0.16] and 0.18 [0.09-0.28], respectively) and weighted minutes of physical activity per week (ß [95% CI], 0.01 [0.003-0.015]). LAVI was not associated with other indexes of left ventricular diastolic dysfunction. There was an effect modification between age and VO2peak/percentage of age- and-sex-predicted VO2peak showing higher LAVI with advanced age and higher VO2peak/percentage of age- and-sex-predicted VO2peak as presented in prediction diagrams. Conclusions Interpretation of LAVI as a marker of diastolic dysfunction should be done in relation to age-relative CRF. Studies on the prognostic value of LAVI in fit subpopulations are needed.

Symptoms of depression and all-cause mortality in farmers, a cohort study: the HUNT study, Norway.

OBJECTIVES: To explore all-cause mortality and the association between symptoms of depression and all-cause mortality in farmers compared with other occupational groups, using a prospective cohort design. METHODS: We included adult participants with a known occupation from the second wave of the Nord-Trøndelag Health Study (Helseundersøkelsen i Nord-Trøndelag 2 (HUNT2) 1995-1997), Norway. Complete information on emigration and death from all causes was obtained from the National Registries. We used the depression subscale of the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of depression. We compared farmers to 4 other occupational groups. Our baseline study population comprised 32 618 participants. Statistical analyses were performed using the Cox proportional hazards models. RESULTS: The estimated mortality risk in farmers was lower than in all other occupations combined, with a sex and age-adjusted HR (0.91, 95% CI 0.82 to 1.00). However, farmers had an 11% increased age-adjusted and sex-adjusted mortality risk compared with the highest ranked socioeconomic group (HR 1.11, 95% CI 0.98 to 1.25). In farmers, symptoms of depression were associated with a 13% increase in sex-adjusted and age-adjusted mortality risk (HR 1.13, 95% CI 0.88 to 1.45). Compared with other occupations this was the lowest HR, also after adjusting for education, marital status, long-lasting limiting somatic illness and lifestyle factors (HR 1.08, 95% CI 0.84 to 1.39). CONCLUSIONS: Farmers had lower all-cause mortality compared with the other occupational groups combined. Symptoms of depression were associated with an increased mortality risk in farmers, but the risk increase was smaller compared with the other occupational groups.