Higher Resting Heart Rate Research Articles

Impact of Anemia on Exercise and Pharmacologic Stress Echocardiography

The safety and diagnostic accuracy of stress testing in anemic patients have not been well studied. Despite a lack of data, significant anemia may be considered a relative contraindication to stress testing because of safety concerns related to insufficient myocardial oxygen supply. The authors reviewed 28,829 consecutive patients with blood hemoglobin drawn within 48hours of stress echocardiography (15,624 exercise and 13,205 dobutamine). The associations of blood hemoglobin concentration with arrhythmia and other stress echocardiographic findings were examined. Additionally, the effect of anemia on the positive predictive value of stress echocardiography for the detection of significant coronary artery stenosis (≥50%) was assessed in patients who subsequently underwent coronary angiography. Anemia was present in 6,401 patients (22.2%) and was severe (hemoglobin < 8.0g/dL) in 52. Stress testing with either exercise or dobutamine was safe, with no significant increase in serious arrhythmia events or need for hospitalization. In the exercise cohort, worsening anemia was associated with reduced treadmill exercise time, lower peak heart rate, peak rate-pressure product, and achieved workload. In the dobutamine stress cohort, worsening anemia was associated with higher resting heart rate, more use of atropine, and fewer patients attaining target heart rate. The positive predictive value of stress echocardiography was higher in patients with moderate anemia compared with those without anemia (71.8% vs 60.2%, P=.01). This study demonstrates that stress testing is safe in patients with mild and moderately anemia, albeit with a small increase in mild supraventricular arrhythmias with exercise. However, worsening anemia was associated with a significant reduction in exercise capacity. Additionally, worsening anemia was associated with an improvement in the positive predictive value of stress echocardiography. Extrapolation of these data to patients with severe anemia should be performed with caution given the limited number of patients with severe anemia in this study.

The impact of time-updated resting heart rate on cause-specific mortality in a random middle-aged male population: a lifetime follow-up

BackgroundA high resting heart rate (RHR) is associated with an increase in adverse events. However, the long-term prognostic value in a general population is unclear. We aimed to investigate the impact of RHR, based on both baseline and time-updated values, on mortality in a middle-aged male cohort.MethodsA random population sample of 852 men, all born in 1913, was followed from age 50 until age 98, with repeated examinations including RHR over a period of 48 years. The impact of baseline and time-updated RHR on cause-specific mortality was assessed using Cox proportional hazard models and cubic spline models.ResultsA baseline RHR of ≥ 90 beats per minute (bpm) was associated with higher all-cause mortality, as compared with an RHR of 60–70 bpm (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.17–2.19, P = 0.003), but not with cardiovascular (CV) mortality. A time-updated RHR of < 60 bpm (HR 1.41, 95% CI 1.07–1.85, P = 0.014) and a time-updated RHR of 70–80 bpm (HR 1.34, 95% CI 1.02–1.75, P = 0.036) were both associated with higher CV mortality as compared with an RHR of 60–70 bpm after multivariable adjustment. Analyses using cubic spline models confirmed that the association of time-updated RHR with all-cause and CV mortality complied with a U-shaped curve with 60 bpm as a reference.ConclusionIn this middle-aged male cohort, a time-updated RHR of 60–70 bpm was associated with the lowest CV mortality, suggesting that a time-updated RHR could be a useful long-term prognostic index in the general population.Graphic abstract

Interactions Between Resting Heart Rate and Childhood Risk Factors in Predicting Convictions and Antisocial Personality Scores

This article analyzes data collected in the Cambridge Study in Delinquent Development, which is a prospective longitudinal study of 411 London males from Ages 8 to 61. It aims to investigate interactions between Age 8 and Age 10 psychosocial risk factors and a biological factor (resting heart rate), measured at Age 18, in predicting convictions up to Age 61 and high antisocial personality scores at Ages 32 and 48 (combined). The present analyses suggest that a high resting heart rate acted as a protective factor against harsh parental discipline and a depressed mother, or conversely that these childhood risk factors predicted antisocial outcomes only when they coincided with a low resting heart rate.

A cohort study on the association between resting heart rate and the risk of new-onset heart failure

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with β-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.

Clinical determinants of the PR interval duration in Swiss middle-aged adults: The CoLaus/PsyCoLaus study.

BackgroundProlonged PR interval (PRi) is associated with adverse outcomes. However, PRi determinants are poorly known. We aimed to identify the clinical determinants of the PRi duration in the general population.HypothesisSome clinical data are associated with prolonged PRi.MethodsCross‐sectional study conducted between 2014 and 2017. Electrocardiogram‐derived PRi duration was categorized into normal or prolonged (>200 ms). Determinants were identified using stepwise logistic regression, and results were expressed as multivariable‐adjusted odds ratio (OR) (95% confidence interval). A further analysis was performed adjusting for antiarrhythmic drugs, P‐wave contribution to PRi duration, electrolytes (kalemia, calcemia, and magnesemia), and history of cardiovascular disease.ResultsOverall, 3655 participants with measurable PRi duration were included (55.6% females; mean age 62 ± 10 years), and 330 (9.0%) had prolonged PRi. Stepwise logistic regression identified male sex (OR 1.41 [1.02‐1.97]); aging (65‐74 years: OR 2.29 [1.61‐3.24], and ≥ 75 years: OR 4.21 [2.81‐6.31]); increased height (per 5 cm, OR 1.15 [1.06‐1.25]); hypertension (OR 1.37 [1.06‐1.77]); and hs troponin T (OR 1.67 [1.15‐2.43]) as significantly and positively associated, and high resting heart rate (≥70 beats/min, OR 0.43 [0.29‐0.62]) as negatively associated with prolonged PRi. After further adjustment, male sex, aging and increased height remained positively, and high resting heart rate negatively associated with prolonged PRi. Hypertension and hs troponin T were no longer associated.ConclusionIn a sample of the Swiss middle‐aged population, male sex, aging and increased height significantly increased the likelihood of a prolonged PRi duration, whereas a high resting heart rate decreased it.

Clinical, hemodynamic, and functional variables affecting success rate of coronary flow velocity reserve detection during vasodilator stress echocardiography.

Stress echocardiography (SE) with state-of-the-art imaging protocol allows a comprehensive assessment of regional wall-motion abnormalities and Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD). We sought to assess the variables potentially impacting on success rate of SE with CFVR. In a single-center, prospective, observational study design, from 2007 to 2019, we enrolled 2989 consecutive patients (age 67±12years; 1723 men) referred for SE, without contrast, for chronic known (n=1130) or suspected (n=1859) coronary syndromes. Coronary flow velocity reserve was measured as stress/rest peak diastolic flow velocity. The same operator (LC) performed all examinations with the same machine (GE Vivid 7). Interpretable CFVR was obtained in 2808 patients (feasibility=93.9%). Overall success rate was lowest (91.4%) in 2007-2008 and steadily rose to 97.8% in 2017-2019 (P for trend <.0001). Feasibility was excellent for men (93.7%) and women (94.3%) (P=.47) across all values of body mass index (BMI): <25 (P=.09), 25-29 (P=.84), and ≥30 (P=.23). At multivariable logistic regression analysis, women with BMI≥30 (OR 1.94, 95% CI 1.14-3.29, P=.02), resting heart rate ≥77beats/min (OR 2.25, 95% CI 1.64-3.11; P<.0001), and stress-induced ischemia in the LAD territory (OR 3.14, 95% CI 1.67-5.90; P<.0001) predicted unfeasible CFVR. Vasodilator SE with CFVR combined with wall-motion analysis is highly feasible also without contrast although with a slight decline in presence of high resting heart rate (reducing diastolic time essential for flow imaging), women with BMI≥30 (increasing tissue thickness interposed between transducer and artery), and anterior ischemia (for underlying low-absent anterograde flow for severely stenotic or occluded LAD).

Polymorphism of the Beta-1 Gly389Arg receptor in patients with dual atrioventricular nodal physiology

IntroductionGly389Arg β1 adrenergic receptor polymorphisms seem to exert an influence on the modulation of the adrenergic effect in several types of patients. This study aimed to determine the prevalence of Gly389Arg polymorphisms among patients with evidence of double nodal pathway and to correlate the electrophysiological properties with the different genotypes of the respective polymorphisms. MethodsA cross-sectional, descriptive and analytical study was designed to assess 49 patients, with evidence of double nodal pathway, submitted to electrophysiological study. Genomic DNA was extracted from peripheral blood leukocytes and the genotypes of the Arg389Gly polymorphisms were identified in all individuals by PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism). ResultsThe majority of patients were female and had supraventricular tachycardia (75.5%). The prevalence of Arg389Arg genotype was found in 32 patients (65.3%), Arg389Gly genotype in 16 patients (32.7%) and Gly389Gly genotype in 1 patient (2%). With respect to the induction of nodal reentrant tachycardia, it was possible to induce non-isoproterenol tachycardia in 32 patients (65.3%), of whom 24 had the Arg389Arg genotype and 8 the Arg389Gly and Gly389Gly genotype (p = 0.05). The resting heart rate of patients of the Arg389Arg genotype was 81 ± 18 bpm and the Arg389Gly and Gly389Gly genotype of 71 ± 9 bpm (p = 0.044). Body mass index (BMI) among patients with genotype Arg389Gly and Gly389Gly was 29.8 ± 7.1 and patients with the Arg389Arg genotype was 26.2 ± 4.6 (p = 0.034). ConclusionThe Arg389Arg genotype was more easily related to triggering arrhythmia, higher resting heart rate and lower BMI.

Influence of an SGLT2 inhibitor, tofogliflozin, on the resting heart rate in relation to adipose tissue insulin resistance

AimsTo examine the effects of a sodium–glucose co‐transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate.MethodsData on 419 participants in tofogliflozin phase 2/3 trials were analysed. Changes in resting heart rate from baseline to week 24 were analysed using an analysis of covariance (ANCOVA) model with groups (tofogliflozin/placebo) as a fixed effect and baseline values as covariates. The antilipolytic effect was evaluated as adipose tissue insulin resistance (Adipo‐IR) and was calculated as the product of fasting insulin and free fatty acid. Multivariate analysis evaluated independent factors for changes in resting heart rate from baseline to week 24.ResultsOf the participants, 58% were men, and mean age, HbA1c, BMI and resting heart rate were 57.6 years, 65 mmol/mol (8.1%), 25.5 kg/m2 and 66 bpm, respectively. At week 24, adjusted mean difference vs. placebo in the change from baseline was −2.3 bpm [95% confidence interval (CI) −4.6, −0.1] with tofogliflozin. Changes in resting heart rate were positively correlated with changes in Adipo‐IR, whereas reductions in HbA1c, body weight and blood pressure were similar independent of changes in resting heart among quartiles of resting heart rate change. On multivariate analysis, higher baseline resting heart rates and Adipo‐IR values were significantly associated with greater reductions in resting heart rate.ConclusionsTofogliflozin corrected resting heart rate levels in accordance with baseline levels. Correction of high resting heart rates may be attributed to improved adipose tissue insulin resistance, leading to correction of hyperinsulinaemia.

Traditional and emerging cardiometabolic risk profiling among Asian youth with type 2 diabetes: A case-control study

BackgroundYouth-onset type 2 diabetes (YT2D) has been associated with high cardiometabolic risk and accelerated progression of diabetes complications. Data on Asian YT2D are limited. AimWe characterized traditional and emerging cardiometabolic risks profile among Asian YT2D and investigated factors that account for the observed differences. MethodsWe compared the cardiometabolic profile in 25 multiethnic Asian YT2D with a mean age of 18.5 ± 4.60 years and disease duration of 23 ± 6 months, with 15 matched controls. Cardiometabolic risks were compared from clinical histories, physical examination, laboratory and radiological investigations. Multiple linear regression models were sequentially adjusted for demographics and metabolic factors to examine possible mechanisms associated with differences in risk profiles between both groups. ResultsDespite similar BMI, YT2D had a higher waist-hip ratio, visceral adiposity, insulin resistance, hs-CRP level and resting heart rate compared to controls (p < 0.05 for all). While LDL-C were similar, YT2D had a lower HDL-C, higher triglyceride, TC:HDL-C and TG:HDL-C ratios (p < 0.05 for all). Nearly two-thirds of YT2D had metabolic syndrome (MetS), with 40% had microalbuminuria and 48% had glomerular hyperfiltration (≥135 ml/min/1.73m2). Subjects with high resting heart rate had four times higher odds of MetS. Eighty percent of YT2D had a cluster of ≥4 risk factors. Adjustment for BMI, HbA1C and blood pressure substantially attenuated differences in cardiometabolic risk factors between both groups, except glomerular filtration remained higher in the YT2D. ConclusionsDespite a relatively short duration of disease, YT2D exhibited high burden of cardiometabolic risk. Glomerular hyperfiltration is associated with YT2D, independent of BMI, HbA1C and blood pressure, suggestive of a causal pathway between the two.National Medical Research Register: NMRR-12-1042-13254.

Thirty-five-year trend in the prevalence of refractive error in Austrian conscripts based on 1.5 million participants

BackgroundTo quantify the current burden of myopia and hyperopia in Austrian young men and the time trend of myopia in the past 35 years by individual and social correlates.MethodWe included...

FLASH Syndrome: Tapping into the Root of Chronic Illness

It has now been established that persons with higher resting heart rates are at increased risk of morbidity and mortality from a plethora of mental and physical illnesses. However, the mechanism underlying the predictive value of this core vital sign remains obscure. This seminal report will integrate clinical, neuropsychological, physiological, and genetic evidence to assert that an inherent hyperexcitability of the neurological system is at the heart of the connection between resting heart rate and disease. Hypothetically, neuronal hyperexcitability can cause multiple circuits in the brain to overfire, including cognitive circuits, limbic circuits, and autonomic circuits, thereby dysregulating the associated systems of the body and allowing the aberration to be detected through standard vital signs and related measures of autonomic activity. Because the cognitive-emotional system is exquisitely sensitive to neuronal excitation, the aberration could also manifest as psychiatric symptomatology, thus suggesting that psychiatric symptoms may be the first subjective markers of the abnormality. Based on the well-recognized link between mental illness, autonomic dysregulation, and systemic disease together with mounting evidence that the related illnesses are associated with gene variants whose protein products fail to adequately regulate the firing of neurons, the vulnerability trait could aptly be called Familial Limbic Autonomic System Hyperexcitability or “FLASH.” Because the trait appears to be so common, its effects so pervasive, and its expression so modifiable, its identification is of critical importance to every medical specialty. FLASH could give clinicians the first comprehensive biological target through which to treat and prevent a plethora of mental, emotional, and physical illnesses.

Effects of environmental enrichment on autonomic nervous activity in NSY mice.

Environmental enrichment (EE) can reduce anxiety and stress in experimental animals, while little is known about the influence on autonomic nervous activity especially in disease animal models. Diabetes mellitus (DM) is associated with cardiovascular autonomic dysfunction, which can be characterized by a higher resting heart rate and a lower heart rate variability (HRV). We hypothesized that EE can enhance parasympathetic nervous activity while reducing disease progression in type 2 diabetic mice. A telemetry transmitter was implanted in NSY mice to continuously record electrocardiograms (ECG). Animals were kept in a cage with or without a nest box as EE. The autonomic nervous activity was evaluated using power spectral analysis of HRV. Four weeks of EE could increase high frequency (HF) power, but no change was observed in the absence of EE. Although animals showed impaired glucose tolerance at 48 weeks of age regardless of EE, a worsen case was observed in control. These results indicate that EE can be necessary for long-term housing of experimental animals and may reduce the risk of impaired glucose tolerance in NSY mice by enhancing parasympathetic nervous activity. In future, it is demanded whether increasing parasympathetic nervous activity, whatever the method is, can prevent diabetes from worsening.

Time-updated resting heart rate predicts mortality in patients with COPD.

High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00-1.87) compared to baseline RHR ≤ 72bpm. The time-updated RHR > 72bpm was markedly superior (HR 1.79, 1.30-2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.

Ideal cardiovascular health and resting heart rate in the Multi-Ethnic Study of Atherosclerosis

Elevated resting heart rate (RHR) is associated with an increased cardiovascular disease (CVD) risk, but little is known about its association with cardiovascular health (CVH), assessed by the Life's Simple 7 (LS7) metrics. We explored whether ideal CVH was associated with RHR in a cohort free from clinical CVD. We conducted a cross-sectional analysis of baseline data (2000−2002) of 6457 Multi-Ethnic Study of Atherosclerosis participants in 2018. Each LS7 metric (smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose) was scored 0–2. Total score ranged from 0 to 14. Scores of 0–8 indicate inadequate, 9–10 average, and 11–14 optimal CVH. RHR was categorized as <60, 60–69, 70–79 and ≥80 bpm. We used multinomial logistic regression to determine associations between CVH score and RHR, adjusting for age, sex, race/ethnicity, education, income, health insurance, and atrioventricular nodal blockers. Mean age of participants (standard deviation) was 62 (10) years; 53% were women; 47% had inadequate CVH, 33% average, and 20% optimal. Favorable CVH was associated with lower odds of having higher RHR. Compared to RHR <60 bpm, participants with optimal CVH had adjusted odds ratio (95% CI) of 0.55 (0.46–0.64) for RHR of 60-69 bpm, 0.34 (0.28–0.43) for 70–79 bpm, and 0.14 (0.09–0.22) for ≥80 bpm. A similar pattern was observed in the stratified analysis by sex, race/ethnicity and age. Favorable CVH was less likely to be associated with elevated RHR irrespective of sex, race/ethnicity and age. More research is needed to explore the usefulness of promoting ideal CVH to reduce elevated RHR, a known risk factor for CVD.

Resting heart rate and mortality in the very old

The number of very old individuals in the population is rapidly increasing. Previous studies have indicated that many factors known to be strongly associated with survival among middle-aged and elderly show no association among the oldest old. Resting heart rate (RHR) is associated with increased risk of death in the general population as well as in patients with various types of heart disease. The association between RHR and mortality in the very old is the subject of this report. The study population was identified in The Nationwide Danish 1905 Cohort Study (n = 1086) and comprised 854 subjects with a median age of 95.2 years (range 94.7–95.9), in whom RHR was measured by radial pulse palpation. Participants were followed until death through the civil registration system, and remaining lifespan after RHR measure was used as outcome. Participants were divided into six groups according to RHR (≤50, 51–60, 61–70, 71–80, 81–90 and ≥91) with the largest group used as the reference group (61–70 beats per minute (bpm)). Survival analyses using Cox’ proportional hazards models were performed to study the association between RHR and mortality. Median RHR was 68 bpm in males (IQR 62–76) and 70 bpm (IQR 64–78) in females. After stratifying both sexes into six groups according to RHR, we found no significant difference in remaining lifespan between groups in either males or females. No significantly increased risk was demonstrated in groups with higher RHR. In very old people, elevated RHR is not associated with increased mortality.

P6474Hidden in plain sight: diastolic blood pressure, resting heart rate and physical examination are independent predictors of mortality in chronic aortic regurgitation

Abstract Background In patients with hemodynamically-significant chronic aortic valve regurgitation (AR), the prognostic significance of routinely-measured diastolic blood pressure (DBP), resting heart rate (RHR) and physical examination signs of heart failure (HF), is unknown. Purpose To investigate the association of DBP, RHR and HF signs, with all-cause mortality. Methods This retrospective cohort study included all consecutive patients with moderately-severe or severe AR within a tertiary-referral center from 2006–2017. Patients with ≥moderate aortic stenosis and those with ≥moderate mitral stenosis/regurgitation were excluded. Results Of 820 patients (age 59±17 years; 82% men) with DBP 64±13mmHg and RHR 64±12bpm, followed for 5.5±3.5 years, 104 died under medical management and 400 underwent aortic valve surgery (AVS). In multivariable analysis, DBP (adjusted-hazard ratio [HR] 0.82 [0.68–0.98] p=0.031, per 10mmHg increase), RHR (adjusted HR 1.2 [1.01–1.41] p=0.034 per 10bpm increase), and any HF signs (adjusted HR 1.66 [1.04–2.61] p=0.032) were associated with all-cause death independently of demographics, comorbidities, and guideline-derived surgical triggers. Mortality increased in a J-curve fashion for DBP starting at 70 mmHg and peaking at 55 mmHg (Fig A,C), and in a linear fashion for RHR starting at 60bpm (Fig B, D). The association persisted after additional adjustment for medications, presence of hypertension and time-dependent AVS. A clinical score combining DBP, RHR and any HF signs increased the mortality risk-discrimination of demographics and comorbidities from 74% to 79% (p=0.01), and from 79% to 82% after addition of surgical triggers (p=0.04). Figure. Risk of death by DBP and RHR Conclusions In patients with AR, routinely-measured vital signs and physical examination are strongly associated with all-cause mortality; lower DBP, higher RHR and any HF signs are independent predictors of mortality, and provide incremental mortality risk-discriminating value to baseline demographics, comorbidities and guideline-derived surgical triggers. These findings represent a clinical paradigm shift and have guideline implications.

Genome-Wide Assessment for Resting Heart Rate and Shared Genetics With Cardiometabolic Traits and Type 2 Diabetes

BackgroundHigh resting heart rate (RHR) occurs in parallel with type 2 diabetes (T2D) and metabolic disorders, implying shared etiology between them. However, it is unknown if they are causally related, and no study has been conducted to investigate the shared mechanisms underlying these associations. ObjectivesThe objective of this study was to understand the genetic basis of the association between resting heart rate and cardiometabolic disorders/T2D. MethodsThis study examined the genetic correlation, causality, and shared genetics between RHR and T2D using LD Score regression, generalized summary data-based Mendelian randomization, and transcriptome wide association scan (TWAS) in UK Biobank data (n = 428,250) and summary-level data for T2D (74,124 cases and 824,006 control subjects) and 8 cardiometabolic traits (sample size ranges from 51,750 to 236,231). ResultsSignificant genetic correlation between RHR and T2D (rg = 0.22; 95% confidence interval: 0.18 to 0.26; p = 1.99 × 10−22), and 6 cardiometabolic traits (fasting insulin, fasting glucose, waist–hip ratio, triglycerides, high-density lipoprotein, and body mass index; rg range −0.12 to 0.24; all p < 0.05) were observed. RHR has significant estimated causal effect on T2D (odds ratio: 1.12 per 10-beats/min increment; p = 7.79 × 10−11) and weaker causal estimates from T2D to RHR (0.32 beats/min per doubling increment in T2D prevalence; p = 6.14 × 10−54). Sensitivity analysis by controlling for the included cardiometabolic traits did not modify the relationship between RHR and T2D. TWAS found locus chr2q23.3 (rs1260326) was highly pleiotropic among RHR, cardiometabolic traits, and T2D, and identified 7 genes (SMARCAD1, RP11-53O19.3, CTC-498M16.4, PDE8B, AKTIP, KDM4B, and TSHZ3) that were statistically independent and shared between RHR and T2D in tissues from the nervous and cardiovascular systems. These shared genes suggested the involvement of epigenetic regulation of energy and glucose metabolism, and AKT activation-related telomere dysfunction and vascular endothelial aging in the shared etiologies between RHR and T2D. Finally, FADS1 was found to be shared among RHR, fasting glucose, high-density lipoprotein, and triglycerides. ConclusionsThese findings provide evidence of significant genetic correlations and causation between RHR and T2D/cardiometabolic traits, advance our understanding of RHR, and provide insight into shared etiology for high RHR and T2D.

Resting heart rate and its dynamic change and the risk of hypertension: The Rural Chinese Cohort Study.

The sex- and age-specific relation in the association of resting heart rate (RHR) and its change and risk of hypertension remains unclear. We prospectively estimated the incidence of hypertension among 9969 nonhypertensive adults participating in The Rural Chinese Cohort Study. Self-reported questionnaires and anthropometric and laboratory measurements were collected at baseline (2007-2008) and follow-up (2013-2014). The modified Poisson regression model was used to calculate relative risk (RR) values and 95% confidence intervals (CIs) for incident hypertension associated with RHR and its dynamic change. During follow-up (median, 6.01 years), 797 (20.28%) men, and 1178 (19.51%) women developed hypertension. Risk of hypertension was increased for women with the highest versus lowest RHR tertile after adjusting for confounding factors (RR: 1.19 [95%CI: 1.04-1.36]) and was associated with increased RHR for women with young age (RR per 10-beat/min RHR increase, 1.25 [95%CI: 1.09-1.43]), middle age (1.06 [0.99-1.14]), and older age (1.11 [1.01-1.23]). Risk of developing hypertension was significantly higher (RR: 1.22 [95%CI: 1.04-1.42]) in women with high RHR (≥80-beat/min) throughout the study period than those with normal RHR (<80-beat/min). No significant association of RHR and hypertension was found in men. RHR is an independent predictor of hypertension in rural Chinese women. Persistently high RHR is associated with increased hypertension risk in women. The dose-response association between RHR and hypertension could be affected by sex and age status.

Resting Heart Rate, Short-Term Heart Rate Variability and Incident Atrial Fibrillation (from the Multi-Ethnic Study of Atherosclerosis (MESA))

Evidence suggests an association between autonomical nervous system (ANS) function and atrial fibrillation (AF) development. We sought to examine the association of baseline resting heart rate (RHR) and short-term heart rate variability (HRV) as surrogates of (ANS) with incident AF in individuals without previous cardiovascular disease. A total of 6,261 participants of the Multi-Ethnic Study of Atherosclerosis who were free of AF and diagnosed cardiovascular disease were enrolled. Three standard 10-second, 12-lead electrocardiograms (ECG) were used to measure RHR, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Cox proportional hazards models adjusted for demographics, atrioventricular nodal agents, and known cardiovascular risk factors were used to examine the association of baseline RHR, and log transformed SDNN and RMSDD with incident AF. Over a mean follow-up of 11.3 ± 3.7 years, 754 (12%) participants developed AF. Spline curve analysis revealed a nonlinear association between RHR, HRV, and incident AF. In fully adjusted models higher (but not lower) baseline RHR (RHR >76 beats/min) was associated with incident AF (hazard ratio 1.48 95% confidence interval 1.18 to 1.86). Additionally, lower values of RMSDD and SDNN and higher values of RMSDD were independently associated with incident AF. In conclusion, cardiac ANS dysregulation indicated as higher RHR and lower HRV is associated with incident AF independent of known cardiovascular risk factors.

Resting Heart Rate and the Risk of Atrial Fibrillation.

In a previous meta-analysis, it was demonstrated that the resting heart rate (RHR) is a potential risk factor for atrial fibrillation (AF). However, the results of that meta-analysis were conflicting, and the relationship between the RHR and AF is still not well established. In the current meta-analysis, our aim is to update evidence with a better statistical model. We searched the Cochrane Library, PubMed, and Embase databases for relevant studies and used a "one-stage approach" with a restricted cubic spline model to summarize the dose-specific relationships between the RHR and AF. Relative risk (RR) was used to measure the effects. In total, 10 studies were included, with a total of 18,630 cases of AF among 431,432 participants. In the dose-response analysis, there was evidence of a nonlinear association between the RHR and the risk of AF (nonlinearity, P < 0.0001), which exhibited a significant J-shaped association between the two factors. An RHR between 68 and 80 bpm had the lowest risk of AF. Among people who had RHR < 70 bpm, the summary RR was 1.09 per 10-RHR decrease (95% confidence interval [CI] = 1.06-1.12; P < 0.001). The results were similar for participants with RHR > 70 bpm (per 10 bpm increase) (RR = 1.06, 95% CI = 1.03-1.08; P < 0.001). Our dose-response meta-analysis revealed a significant J-shaped association between the RHR and AF. Both low RHR and high RHR were associated with an increased risk of AF compared with a modest RHR of 68-80 bpm.