Javaid Nauman

Temporal changes in resting heart rate and deaths from ischemic heart disease.

CONTEXT Resting heart rate (RHR) has long been recognized as an independent predictor of cardiovascular risk. However, whether temporal changes in RHR influence the risk of death from ischemic heart disease (IHD) in the general population is not known. OBJECTIVE To assess the association of long-term longitudinal changes in RHR with the risk of dying from IHD. DESIGN, SETTINGS, AND PARTICIPANTS A prospective cohort study of 13,499 men and 15,826 women without known cardiovascular disease in Norway. Resting heart rate was measured on 2 occasions around 10 years apart in the Nord-Trøndelag County Health Study. The second RHR measurement was obtained between August 1995 and June 1997, with subsequent mortality follow-up until December 31, 2008. A total of 60 participants were lost to follow-up, all due to emigration from Norway. Using Cox regression analyses, adjusted hazard ratios (AHRs) were estimated of death from IHD related to changes in RHR over time. In a corresponding analysis, death from all causes also was assessed. RESULTS During a mean (SD) of 12 (2) years of follow-up, 3038 people died, and 388 deaths were caused by IHD. An increase in RHR was associated with increased risk of death from IHD. Compared with participants with a RHR of less than 70 beats/min at both measurements (8.2 deaths/10,000 person-years), the AHR was 1.9 (95% CI, 1.0-3.6) for participants with a RHR of less than 70 beats/min at the first measurement but greater than 85 beats/min at the second measurement (17.2 deaths/10,000 person-years). For participants with RHRs between 70 and 85 beats/min at the first measurement and greater than 85 beats/min at the second measurement (17.4 deaths/10,000 person-years), the AHR was 1.8 (95% CI, 1.2-2.8). The association of change in RHR with IHD mortality was not linear (P = .003 for quadratic trend), suggesting that a decrease in RHR showed no general mortality benefit. Excluding the first 3 years of follow-up did not substantially alter the findings. The associations for total mortality were similar but generally weaker than those observed for IHD mortality. CONCLUSION Among men and women without known cardiovascular disease, an increase in RHR over a 10-year period was associated with increased risk of death from IHD and also for all-cause mortality.

Telomere Length and Long-Term Endurance Exercise: Does Exercise Training Affect Biological Age? A Pilot Study

Background Telomeres are potential markers of mitotic cellular age and are associated with physical ageing process. Long-term endurance training and higher aerobic exercise capacity (VO2max) are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO2max has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise training and VO2max in younger and older people. Methods Twenty men; 10 young (22–27 years) and 10 old (66–77 years), were studied in this cross-sectional study. Five out of 10 young adults and 5 out of 10 older were endurance athletes, while other halves were exercising at a medium level of activity. Mean telomere length was measured as telomere/single copy gene-ratio (T/S-ratio) using quantitative real time polymerase chain reaction. VO2max was measured directly running on a treadmill. Results Older endurance trained athletes had longer telomere length compared with older people with medium activity levels (T/S ratio 1.12±0.1 vs. 0.92±0.2, p = 0.04). Telomere length of young endurance trained athletes was not different than young non-athletes (1.47±0.2 vs. 1.33±0.1, p = 0.12). Overall, there was a positive association between T/S ratio and VO2max (r = 0.70, p = 0.001). Among endurance trained athletes, we found a strong correlation between VO2max and T/S ratio (r = 0.78, p = 0.02). However, corresponding association among non-athlete participants was relatively weak (r = 0.58, p = 0.09). Conclusion Our data suggest that VO2max is positively associated with telomere length, and we found that long-term endurance exercise training may provide a protective effect on muscle telomere length in older people.

Even low level of physical activity is associated with reduced mortality among people with metabolic syndrome, a population based study (the HUNT 2 study, Norway)

BackgroundLow levels of physical activity may increase the risk of developing metabolic syndrome, a cluster of metabolic factors that are associated with the risk of premature death. It has been suggested that physical activity may reduce the impact of factors associated with metabolic syndrome, but it is not known whether physical activity may reduce mortality in people with metabolic syndrome.MethodsIn a prospective study of 50,339 people, 13,449 had metabolic syndrome at baseline and were followed up for ten years to assess cause-specific mortality. The population was divided into two age groups: those younger than 65 years of age and those older than age 65. Information on their physical activity levels was collected at baseline.ResultsMetabolic syndrome was associated with higher mortality from all causes (hazard ratio (HR) 1.35, 95% confidence interval (95% CI) 1.20 to 1.52) and from cardiovascular causes (HR 1.78, 95% CI 1.39 to 2.29) in people younger than 65 years old than among other populations. In older people, there was no overall association of metabolic syndrome with mortality. People with metabolic syndrome who reported high levels of physical activity at baseline were at a reduced risk of death from all causes compared to those who reported no physical activity, both in the younger age group (HR 0.52, 95% CI 0.37 to 0.73) and in the older age group (HR 0.59, 95% CI 0.47 to 0.74).ConclusionAmong people with metabolic syndrome, physical activity was associated with reduced mortality from all causes and from cardiovascular causes. Compared to inactivity, even low levels of physical activity were associated with reduced mortality.

A simple nonexercise model of cardiorespiratory fitness predicts long-term mortality.

PURPOSE Cardiorespiratory fitness (CRF) is a strong predictor of future health, but measurements of CRF are time consuming and involve costly test procedures. We assessed whether a simple, non-exercise-based test of CRF predicted long-term all-cause and cardiovascular disease (CVD) mortality. METHODS In this prospective cohort study, we used a previously published nonexercise test to estimate CRF in healthy men (n = 18,348) and women (n = 18,764) from the first HUNT study (1984-1986) in Norway. We used Cox regression to obtain HR for mortality during a mean follow-up of 24 yr. Assessment of model validity was performed by standard procedures of discrimination and calibration. RESULTS CRF was inversely associated with all-cause and CVD mortality in men and women below 60 yr of age at baseline, after adjustment for confounders. For each MET-higher CRF (MET, approximately 3.5 mL·kg·min), HR for CVD mortality was 21% lower in both men (95% confidence interval (CI), 17%-26%) and women (95% CI, 12%-29%). HR for all-cause mortality was 15% (95% CI, 12%-17%) lower in men and 8% (95% CI, 3%-3%) lower in women for each MET-higher CRF. The ability of the model to discriminate mortality risk among participants below 60 yr was better for CRF (area under the curve (AUC), 0.70-0.77) compared with that for each variable that constituted the model (AUC, 0.55-0.63) and an aggregated sum of z-scores for each variable (AUC, 0.61-0.65). Comparison of observed and predicted risk indicated good model calibration. CONCLUSIONS This method of assessing CRF is feasible and practically useful in primary care for identification of apparently healthy individuals at increased risk of premature CVD disease and all-cause mortality.

Physical Activity as a Long-Term Predictor of Peak Oxygen Uptake: The HUNT Study

INTRODUCTION A physically active lifestyle and a relatively high level of cardiorespiratory fitness are important for longevity and long-term health. No population-based study has prospectively assessed the association of physical activity levels with long-term peak oxygen uptake (VO(2peak)). METHODS 1843 individuals (906 women and 937 men) who were between 18 and 66 yr at baseline and were free from known lung or heart diseases at both baseline (1984-1986) and follow-up (2006-2008) were included in the study. Self-reported physical activity was recorded at both occasions, and VO(2peak) was measured at follow-up. The association of physical activity levels and VO(2peak) was adjusted for age, level of education, smoking status, and weight change from baseline to follow-up, using ANCOVA statistics. RESULTS The level of physical activity at baseline was strongly associated with VO(2peak) at follow-up 23 yr later in both men and women (Ptrends < 0.001). Compared with individuals who were inactive at baseline, women and men who were highly active at baseline had higher (3.3 and 4.6 mL·kg(-1)·min(-1)) VO(2peak) at follow-up. Women who were inactive at baseline but highly active at follow-up had 3.7 mL·kg(-1)·min(-1) higher VO(2peak) compared with women who were inactive both at baseline and at follow-up. The corresponding comparison in men showed a difference of 5.2 mL·kg(-1)·min(-1) (95% confidence interval = 3.1-7.3) in VO(2peak). CONCLUSIONS Physical activity level at baseline was positively associated with directly measured cardiorespiratory fitness (VO(2peak)) 23 yr later. People who changed from low to high activity during the observation period had substantially higher V˙O(2peak) at follow-up compared with people whose activity remained low.

Circulating microRNAs predict future fatal myocardial infarction in healthy individuals – The HUNT study

Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants. We performed a prospective nested case-control study with 10-year observation period and fatal AMI as endpoint. In total, 179 miRs were quantified by real-time polymerase chain reaction in serum of 112 healthy participants (40-70years) that either (1) suffered from fatal AMI within 10years [n=56], or (2) remained healthy [n=56, risk factor-matched controls]. Candidate miRs were validated in a separate cohort of healthy individuals (n=100). Twelve miRs were differently expressed in cases and controls in the derivation cohort (p<0.05). Among these, 10 miRs differed significantly between cases and controls in the validation cohort (p<0.05). We identified gender dimorphisms, as miR-424-5p and miR-26a-5p were associated exclusively with risk in men and women, respectively. The best model for predicting future AMI consisted of miR-106a-5p, miR-424-5p, let-7g-5p, miR-144-3p and miR-660-5p, providing 77.6% correct classification for both genders, and 74.1% and 81.8% for men and women, respectively. Adding these 5 miRs to the Framingham Risk Score, increased the AUC from 0.72 to 0.91 (p<0.001). In conclusion, we identified several miRs associated with future AMI, revealed gender-specific associations, and proposed a panel of 5 miRs to enhance AMI risk prediction in healthy individuals.

Current physical activity guidelines for health are insufficient to mitigate long-term weight gain: more data in the fitness versus fatness debate (The HUNT study, Norway)

Background To promote and maintain health, all adults are recommended to do moderate-intensity aerobic activity a minimum of 30 min on 5 days, or vigorous-intensity activity of 20 min on 3 days, each week. Whether these levels prevent long-term weight gain is uncertain. Objective To assess the relationship between physical activity and long-term weight gain. Study design An observational prospective cohort study. Methods Weight and physical activity were measured in the Nord-Trøndelag Health Study in 1984–1986, 1995–1997 and 2006–2008. Participants (n=19 127) were classified based on physical activity into inactive, below recommended level, recommended level or above recommended level. We carried out adjusted mixed model regression analyses with weight as outcome. Results Men maintaining physical activity above the recommendations for 33 years increased 5.6 kg, while inactive men increased 9.1 kg. For women, corresponding numbers were 3.8 kg in those above recommended physical activity levels, and 9.5 kg in inactive. In adjusted analyses, physical activity above the recommendations was associated with 2.1 kg (95% CI 1.8 to 2.4) less weight gain in men over any 11-year period, compared with inactive. Women exceeding the recommendations gained 1.8 kg (CI 1.5 to 2.2) less than inactive. Compared with inactive, the ORs of gaining meaningful weight of ≥2.3 kg were 0.79 (CI 0.69 to 0.91) and 0.70 (CI 0.60 to 0.81) if exceeding the recommendations in men and women, respectively. Conclusions Physical activity above the current recommendations for health benefits was associated with significantly lower risk of weight gain.

Combined effect of resting heart rate and physical activity on ischaemic heart disease: mortality follow-up in a population study (the HUNT study, Norway)

Background The combined effect of resting heart rate (RHR) and physical activity (PA) on ischaemic heart disease (IHD) has never been assessed. The objective of this study was to assess the association of RHR with IHD mortality, and to evaluate the potentially modifying effect of PA on this association. Methods In a prospective cohort study of 24 999 men and 25 089 women free from cardiovascular disease at baseline, Cox proportional hazard models were used to estimate adjusted hazard ratios of death from IHD related to RHR measured at baseline. The combined effect of RHR and self-reported PA on the risk of death from IHD was also assessed. Results During a mean of 18.2 (SD 4) years of follow-up, 2566 men and 1814 women died from cardiovascular causes. For each increment of 10 heart beats per minute, risk of death from IHD was 18% higher in women <70 years of age (p<0.001); no such association was observed among women ≥70 years. Among men, there was a corresponding 10% higher risk in the younger (p = 0.004), and 11% higher risk in the older age group (p = 0.01). Among women, the risk associated with high RHR was substantially attenuated in those who reported a high level of PA, whereas in men, there was no clear indication that PA could modify the positive effect of RHR. Conclusion RHR is positively associated with the risk of death from IHD, and among women, the results suggest that by engaging in PA, the risk associated with a high RHR may be substantially reduced.

Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension

Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension. Specifically, the empirically observed chronic changes in pulse pressure with age and the impaired capacity of hypertensive individuals to regulate short-term changes in blood pressure arise as emergent properties of the integrated system. The results are consistent with available experimental data from chemical and surgical manipulation of the cardio-vascular system. In contrast to widely held opinions, the results suggest that primary hypertension can be attributed to a mechanogenic etiology without challenging current conceptions of renal and sympathetic nervous system function.

A Prospective Population Study of Resting Heart Rate and Peak Oxygen Uptake (the HUNT Study, Norway)

Objectives We assessed the prospective association of resting heart rate (RHR) at baseline with peak oxygen uptake (VO2peak) 23 years later, and evaluated whether physical activity (PA) could modify this association. Background Both RHR and VO2peak are strong and independent predictors of cardiovascular morbidity and mortality. However, the association of RHR with VO2peak and modifying effect of PA have not been prospectively assessed in population studies. Methods In 807 men and 810 women free from cardiovascular disease both at baseline (1984–86) and follow-up 23 years later, RHR was recorded at both occasions, and VO2peak was measured by ergospirometry at follow-up. We used Generalized Linear Models to assess the association of baseline RHR with VO2peak, and to study combined effects of RHR and self-reported PA on later VO2peak. Results There was an inverse association of RHR at baseline with VO2peak (p<0.01). Men and women with baseline RHR greater than 80 bpm had 4.6 mL·kg−1·min−1 (95% confidence interval [CI], 2.8 to 6.3) and 1.4 mL·kg−1·min−1 (95% CI, −0.4 to 3.1) lower VO2peak at follow-up compared with men and women with RHR below 60 bpm at baseline. We found a linear association of change in RHR with VO2peak (p = 0.03), suggesting that a decrease in RHR over time is likely to be beneficial for cardiovascular fitness. Participants with low RHR and high PA at baseline had higher VO2peak than inactive people with relatively high RHR. However, among participants with relatively high RHR and high PA at baseline, VO2peak was similar to inactive people with relatively low RHR. Conclusion RHR is an important predictor of VO2peak, and serial assessments of RHR may provide useful and inexpensive information on cardiovascular fitness. The results suggest that high levels of PA may compensate for the lower VO2peak associated with a high RHR.