Physical Exertion Immediately Before Early Preterm Delivery: A Case-Crossover Study.

BACKGROUND: Occupational exertion is associated with a higher risk of preterm delivery, although studies of leisure time activities generally document reduced risks. Less is known about the risk of preterm delivery immediately following episodes of moderate or heavy physical exertion. METHODS: We conducted a case-crossover study of 722 women interviewed during their hospital stay for early preterm delivery, defined by a gestational age before 34 weeks, and after 20 weeks. Interviews occurred between March 2013 and December 2015 in seven hospitals in Lima, Peru. RESULTS: The incidence rate ratio (RR) of early preterm delivery was 5.82-fold higher (95% confidence interval [CI] = 4.29, 7.36) in the hour following moderate or heavy physical exertion compared with other times and returned to baseline in the hours thereafter. The RR of early preterm delivery within an hour of physical exertion was lower for exertion at moderate intensity (RR = 2.43; 95% CI = 1.50, 3.96) than at heavy intensity (RR = 23.62; 95% CI = 15.54, 35.91; P-homogeneity < 0.001). The RR of early preterm delivery was lower in the hour following moderate physical exertion among women who habitually engaged in physical exertion >3 times per week in the year before pregnancy (RR = 1.56; 95% CI = 0.81, 3.00) compared with more sedentary women (RR = 6.91; 95% CI = 3.20, 14.92; P-homogeneity = 0.003). CONCLUSIONS: Our study showed a heightened risk of early preterm delivery in the hour following moderate or heavy physical exertion.

Relation of outbursts of anger and the acute risk of placental abruption: A case-crossover study.

BACKGROUND: Roughly, a fourth of all placental abruption cases have an acute aetiologic underpinning, but the causes of acute abruption are poorly understood. Studies indicate that symptoms of stress, depression, and anxiety during pregnancy may be associated with a higher risk of abruption. OBJECTIVE: We examined the rate of abruption in the 2 hours immediately following outbursts of anger. METHODS: In a multicentre case-crossover study, we interviewed 663 women diagnosed with placental abruption admitted to one of the seven Peruvian hospitals between January 2013 and August 2015. We asked women about outbursts of anger before symptom onset and compared this with their usual frequency of anger during the week before abruption. RESULTS: The rate of abruption was 2.83-fold (95% confidence interval [CI] 1.85, 4.33) higher in the 2 hours following an outburst of anger compared with other times. The rate ratio (RR) was lower for women who completed technical school or university (RR 1.38, 95% CI 0.52, 3.69) compared to women with secondary school education or less (RR 3.73, 95% CI 2.32, 5.99, P-homogeneity = .07). There was no evidence that the association between anger episodes and abruption varied by hypertensive disorders of pregnancy (ie preeclampsia/ eclampsia) or antepartum depressive symptoms. CONCLUSION: There was a higher rate of abruption in the 2 hours following outbursts of anger compared with other times, providing potential clues to the aetiologic mechanisms of abruption of acute onset.

Physical Exertion Immediately Prior to Placental Abruption: A Case-Crossover Study.

While there is consistent evidence that episodes of physical exertion are associated with an immediately higher risk of acute ischemic vascular events, the risk of placental abruption immediately following episodes of physical exertion has not been studied. In a multicenter case-crossover study, we interviewed 663 women with placental abruption at 7 Peruvian hospitals between January 2013 and August 2015. We asked women about physical exertion in the hour before symptom onset and compared this with their frequency of physical exertion over the prior week. Compared with times with light or no exertion, the risk of placental abruption was 7.8 (95% confidence interval (CI): 5.5, 11.0) times greater in the hour following moderate or heavy physical exertion. The instantaneous incidence rate ratio of placental abruption within an hour of moderate or heavy physical exertion was lower for women who habitually engaged in moderate or heavy physical activity more than 3 times per week in the year before pregnancy (rate ratio (RR) = 3.0, 95% CI: 1.6, 5.9) compared with more sedentary women (RR = 17.3, 95% CI: 11.3, 26.7; P for homogeneity < 0.001), and the rate ratio was higher among women with preeclampsia/eclampsia (RR = 13.6, 95% CI: 7.0, 26.2) than among women without (RR = 6.7, 95% CI: 4.4, 10.0; P for homogeneity = 0.07).

Alcohol and Immediate Risk of Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND: Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the immediate risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on immediate and long-term risk. METHODS AND RESULTS: We searched CINAHL, Embase, and PubMed from inception to March 12, 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks and 95% confidence intervals for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke using DerSimonian and Laird random-effects models to model any alcohol intake or dose-response relationships of alcohol intake and cardiovascular events. Among 1056 citations and 37 full-text articles reviewed, 23 studies (29 457 participants) were included. Moderate alcohol consumption was associated with an immediately higher cardiovascular risk that was attenuated after 24 hours, and even protective for myocardial infarction and hemorrhagic stroke (≈2-4 drinks: relative risk=30% lower risk) and protective against ischemic stroke within 1 week (≈6 drinks: 19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6-9 drinks: relative risk=1.3-2.3) and week (≈19-30 drinks: relative risk=2.25-6.2). CONCLUSIONS: There appears to be a consistent finding of an immediately higher cardiovascular risk following any alcohol consumption, but, by 24 hours, only heavy alcohol intake conferred continued risk.

Immediate risk of myocardial infarction following physical exertion, tea, and coffee: A case-crossover study in Thailand.

BACKGROUND: Physical exertion and caffeine consumption are associated with acute myocardial infarction (MI). However, physical exertion and caffeine consumption have not been examined as immediate triggers of MI in low and middle-income countries. OBJECTIVE: Using a self-matched case-crossover design, we examined the acute risk of MI in the hour following episodes of physical exertion, caffeinated coffee, and tea consumption among MI survivors in Thailand. METHODS: A total of 506 Thai participants (women = 191, men = 315) were interviewed between 2014 and 2017 after sustaining an acute MI. We compared each subject's exposure to physical exertion and consumption of caffeine- containing beverages in the hour preceding the onset of MI with the subject's expected usual frequency in the prior year to calculate relative risks (RRs) and 95% confidence intervals (95%CIs). RESULTS: Of the 506 participants, 47 (9.3%) engaged in moderate or heavy physical exertion, 6 (1.2%) consumed tea, and 21 (4.2%) consumed coffee within the hour before MI. The relative risk of MI after moderate or heavy physical exertion was 3.0 (95% CI 2.2-4.2) compared to periods of no exertion, with a higher risk among more sedentary participants compared to active participants. Compared to times with no caffeinated beverage consumption, there was a higher risk of MI in the hour following consumption of caffeinated tea (RR = 3.7; 95%CI: 1.5-9.3) and coffee (RR = 2.3; 95%CI: 1.4-3.6). CONCLUSION: Physical exertion, coffee and tea consumption were associated with a higher risk of MI in the subsequent hour compared to times when the participants were sedentary or did not consume caffeinated beverages. Our study identifies high-risk populations for targeted screening and intervention to prevent acute MI.

Chocolate intake and risk of clinically apparent atrial fibrillation: the Danish Diet, Cancer, and Health Study.

OBJECTIVE: To evaluate the association between chocolate intake and incident clinically apparent atrial fibrillation or flutter (AF). METHODS: The Danish Diet, Cancer, and Health Study is a large population-based prospective cohort study. The present study is based on 55 502 participants (26 400 men and 29 102 women) aged 50-64 years who had provided information on chocolate intake at baseline. Incident cases of AF were ascertained by linkage with nationwide registries. RESULTS: During a median of 13.5 years there were 3346 cases of AF. Compared with chocolate intake less than once per month, the rate of AF was lower for people consuming 1-3 servings/month (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.82 to 0.98), 1 serving/week (HR 0.83, 95% CI 0.74 to 0.92), 2-6 servings/week (HR 0.80, 95% CI 0.71 to 0.91) and ≥1 servings/day (HR 0.84, 95% CI 0.65 to 1.09; p-linear trend <0.0001), with similar results for men and women. CONCLUSIONS: Accumulating evidence indicates that moderate chocolate intake may be inversely associated with AF risk, although residual confounding cannot be ruled out.

PSD-95 regulates CRFR1 localization, trafficking and ß-arrestin2 recruitment.

Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif-dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress ß-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness.

Aerobic Fitness and Risk of Ventricular Arrhythmia Following Physical Exertion.

BACKGROUND: Brief episodes of physical exertion are associated with an immediately greater risk of cardiovascular events. Previous studies on the risk of ventricular arrhythmia (VA) shortly after exertion have not assessed if this risk differs according to the level of aerobic fitness or sedentary behaviour. Therefore, we conducted a prospective cohort study of patients with implantable cardioverter-defibrillators (ICDs) with a nested case-crossover analysis to examine the risk of VA shortly after exertion and whether this risk is modified by aerobic fitness and sedentary behaviour. METHODS: Ninety-seven consecutive patients were recruited at the time of ICD implantation and 30 confirmed events occurred among patients who completed interviews about physical exertion preceding ICD therapy. We compared the frequency of exertion within an hour of ICD discharge to each patient's usual frequency of exertion reported at the time of ICD implantation. RESULTS: Within an hour of episodes of exertion, the risk of VA was 5.3 (95% confidence interval [CI], 2.7-10.6) times greater compared with periods of rest. The association was higher among patients with aerobic fitness below the median (relative risk [RR] = 17.5; 95% CI, 5.2-58.5) than for patients with aerobic fitness above the median (RR, 1.2; 95% CI, 0.4-4.2; P homogeneity = 0.002) and higher among patients who were sedentary (RR, 52.8; 95% CI, 10.1-277) compared with individuals who were not sedentary (RR, 3.2; 95% CI, 1.3-7.6; P homogeneity = 0.0002). CONCLUSIONS: Within 1 hour of episodes of exertion, there is an increased risk of VA, especially among individuals with lower levels of aerobic fitness and with sedentary behaviour.