Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population

Jouven, Xavier; Schwartz, Peter J.; Escolano, Sylvie; Straczek, Céline; Tafflet, Muriel; Desnos, Michel; Empana, Jean Philippe; Ducimetière, Pierre

doi:10.1093/eurheartj/ehp160

Cited by 44 publications

(24 citation statements)

References 28 publications

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“…The identification of those in the population who are at higher risk of sudden death remains a major challenge, as nearly half of the victims are asymptomatic, and successful resuscitation outside a hospital is rare. We and others previously reported significant associations between traditional and nontraditional risk factors with sudden death, [3][4][5][6][7][8][9] but these factors are not sufficiently sensitive to identify those who are at higher risk. Therefore, new risk markers need to be investigated.…”

mentioning

confidence: 76%

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

Empana

Jouven

Canouï‐Poitrine

et al. 2010

ATVB

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Objective-To examine prospectively the association of high-sensitivity C-reactive protein, interleukin 6, and fibrinogen with sudden death in asymptomatic European men. Methods and Results-Among the 9771 men from the Etude PRospective de l'Infarctus du Myocarde (PRIME) Study, 664 had a first coronary heart disease over 10 years, including 50 sudden deaths, 34 nonsudden coronary deaths, and 580 nonfatal coronary heart disease events. For each outcome, 2 matched controls, who were free of coronary heart disease at the index date, were randomly selected from the initial cohort (nested case control study design). There was a 3-fold increased risk (95% CI, 1.20 to 7.81) of sudden death between the upper and the lower third of interleukin 6 after adjustment for baseline confounders in conditional logistic regression analysis. Neither high-sensitivity C-reactive protein (hazard ratio third versus first tertile ϭ1.27; 95% CI, 0.51 to 3.17) nor fibrinogen (hazard ratio third versus first tertile ϭ1.90; 95% CI, 0.76 to 4.75) was associated with sudden death. For comparison, there was a 6-fold increased risk of nonsudden coronary death from the highest compared with the lowest tertile of fibrinogen and a trend toward an association with higher C-reactive protein and higher interleukin 6. All 3 inflammatory biomarkers were moderately, but significantly, associated with nonfatal coronary heart disease. Conclusion-Interleukin 6, but not high-sensitivity C-reactive protein or fibrinogen, is an independent predictor of sudden death in asymptomatic European men.

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mentioning

confidence: 76%

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

Empana

Jouven

Canouï‐Poitrine

et al. 2010

ATVB

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“…Moreover, these variability criteria are computed for the entire ECG-Holter recordings, regardless of the duration and concomitant activities and stresses the subjects experience. We have previously shown in the Paris Prospective Study I that HR at rest, during exercise and recovery, and during mental stress were associated with total mortality and sudden death in particular [5][6][7]. With the contemporary PPS3, these specific periods will be studied more in depth to propose novel heart rate parameters of potential interest.…”

Section: Discussionmentioning

confidence: 98%

“…Imbalance between the sympathetic and the vagal tone is suggested to be the main underlying mechanism related to sudden death susceptibility [4]. For example, through the Paris Prospective Study I, our group previously showed that heart rate (HR) at rest, just before exercise and during or after an exercise test was a particular strong and specific marker of sudden death risk compared to non-sudden coronary death [5][6][7]. However, these results, which mostly reflect the effect of one single HR measure, were obtained in men only and concerned baseline measurements that were performed in the late 60's, before the era of beta blocking agents.…”

Section: Introductionmentioning

confidence: 99%

Paris Prospective Study III: a study of novel heart rate parameters, baroreflex sensitivity and risk of sudden death

Empana

Bean²,

Guibout

et al. 2011

Eur J Epidemiol

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Resting heart rate has been related to the risk of cardiovascular disease and sudden death in several large prospective studies. To investigate prospectively the association of novel heart rate parameters and of carotid artery stiffness with sudden death and other cardiovascular disease. The Paris Prospective Study III (PPS3) is a new, ongoing French prospective study. From June 2008 to December 2011, 10,000 men and women aged 50-75 years who will have a preventive medical check-up at the Centre d'Investigations Préventives et Cliniques in Paris (France), will be enrolled in the study, after signing an informed consent. In addition to the general health examination, each subject's heart rhythm will be recorded during the course of the health check-up (approximately 2(1/2) h) and an echo-tracking of the right carotid bulb will be performed by trained technicians. A bio bank and DNA bank will be established for further biomarker and genetic analyses. The occurrence of cardiovascular disease including acute coronary syndrome, stroke, peripheral artery disease and sudden death, and of mortality, of the participants will be followed up during 20 years. With an estimated mean annual rate of sudden death of 0.1% and its increasing incidence rate with age, between 250 and 300 sudden deaths are expected. This unique study should provide new insights into the regulation of heart rate and blood pressure and should enable to identify novel heart rate parameters that are associated with sudden death.

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“…By contrast, sudden centrally mediated sympathetic activation elicits a mostly localized release of norepinephrine from neural terminals, which increases both regional heterogeneity and cardiac electrical instability. This explains the profound difference in the correlation between sudden death and HR responses during exercise and mental stress 23 . Thus, it had to be expected that uniform beta-adrenergic stimulation by isoproterenol perfusion would reduce the dispersion of repolarization caused by anthopleurin (which augments late I Na ), and that this “beneficial” effect produced by stimulation of beta-adrenergic receptors would be prevented by propranolol, a drug whose function is blocking the beta-receptors.…”

Section: Discussionmentioning

confidence: 99%

Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: Implications for the clinical management of LQT3 patients

et al. 2014

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BackgroundThe efficacy of beta-blockers for treatment of patients with long QT syndrome type 3 (LQT3) has been repeatedly questioned, and it has been suggested that they might be detrimental for this genetic subgroup of patients with long QT syndrome (LQTS). The disquieting consequence has been that cardiologists confronted with LQT3 patients often do not even attempt pharmacologic therapy and implant cardioverter-defibrillators as first-choice treatment. However, the most recent clinical data indicate high efficacy of beta-blocker therapy in LQT3 patients.ObjectiveThe purpose of this study was to test the antiarrhythmic efficacy of beta-blockers in an established experimental model for LQT3.MethodsAfter phenotypic validation of 65 ∆KPQ-SCN5A knock-in transgenic (TG) mice compared to 32 wild-type (WT) mice, we tested the effect of the arrhythmogenic cholinergic muscarinic agonist carbachol in 19 WT and 39 TG anesthetized mice, with and without pretreatment with propranolol given intraperitoneally.ResultsAt the same heart rates, TG mice had a markedly longer QT interval than WT mice. Whereas carbachol had minor arrhythmic effects in the WT mice, it produced ventricular tachycardia (VT) and ventricular fibrillation (VF) in 55% of 20 TG mice. By contrast, in none of 19 TG mice pretreated with propranolol did VT/VF occur after carbachol injection.ConclusionThese experimental data indicate that, contrary to previous reports, beta-blockade effectively prevents VT/VF in a validated LQT3 model. Together with the most recent clinical data, these findings indicate that there is no reason for not initiating protective therapy with beta-blockers in LQT3 patients.

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Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population

Abstract: An important heart rate increase produced by a mild mental stress predicts long-term risk for sudden cardiac death. Heart rate changes before an exercise test may provide a simple tool for risk stratification.

Cited by 44 publications

References 28 publications

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

Paris Prospective Study III: a study of novel heart rate parameters, baroreflex sensitivity and risk of sudden death

Propranolol prevents life-threatening arrhythmias in LQT3 transgenic mice: Implications for the clinical management of LQT3 patients

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