Resting heart rate and the risk of cardiovascular disease, total cancer, and all-cause mortality - A systematic review and dose-response meta-analysis of prospective studies.

BACKGROUND AND AIM: Epidemiological studies have reported increased risk of cardiovascular disease, cancer and all-cause mortality with greater resting heart rate, however, the evidence is not consistent. Differences by gender, adjustment for confounding factors, as well as the potential impact of subclinical disease are not clear. A previous meta-analysis missed a large number of studies, and data for atrial fibrillation have not been summarized before. We therefore aimed to clarify these associations in a systematic review and meta-analysis of prospective studies. METHODS AND RESULTS: PubMed and Embase were searched up to 29 March 2017. Summary RRs and 95% confidence intervals (CIs) were calculated using random effects models. Eighty seven studies were included. The summary RR per 10 beats per minute increase in resting heart rate was 1.07 (95% CI: 1.05-1.10, I2 = 61.9%, n = 31) for coronary heart disease, 1.09 (95% CI: 1.00-1.18, I2 = 62.3%, n = 5) for sudden cardiac death, 1.18 (95% CI: 1.10-1.27, I2 = 74.5%, n = 8) for heart failure, 0.97 (95% CI: 0.92-1.02, I2 = 91.4%, n = 9) for atrial fibrillation, 1.06 (95% CI: 1.02-1.10, I2 = 59.5%, n = 16) for total stroke, 1.15 (95% CI: 1.11-1.18, I2 = 84.3%, n = 35) for cardiovascular disease, 1.14 (95% CI: 1.06-1.23, I2 = 90.2%, n = 12) for total cancer, and 1.17 (95% CI: 1.14-1.19, I2 = 94.0%, n = 48) for all-cause mortality. There was a positive dose-response relationship for all outcomes except for atrial fibrillation for which there was a J-shaped association. CONCLUSION: This meta-analysis found an increased risk of coronary heart disease, sudden cardiac death, heart failure, atrial fibrillation, stroke, cardiovascular disease, total cancer and all-cause mortality with greater resting heart rate.

Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway.

BACKGROUND: Adult weight gain is associated with increased risk of postmenopausal breast cancer. Most previous studies are limited by using recalled or self-reported data, and it is not known if age-specific weight changes are important for breast cancer risk. METHODS: In a Norwegian cohort of 28,153 women (and 900 incident breast cancers) with longitudinal anthropometric measurements over up to 30 years, we studied both overall and age-related weight changes in adulthood and risk of postmenopausal breast cancer. RESULTS: Overall, weight gain in adulthood was associated with increased breast cancer risk (hazard ratio (HR) per kg per year 1.31, 95% confidence interval (CI) 1.11-1.54). Weight gain before (HR per kg per year 1.38, 95% CI 1.09-1.75) or around menopause (1.69, 95% CI 1.32-2.16) was associated with increased risk, but there was no clear risk increase associated with later weight gain (HR per kg per year 0.92, 95% CI 0.73-1.18). CONCLUSION: Weight gain in adulthood was associated with increased risk of breast cancer. Our results suggest that weight gain before and around menopausal age may be particularly important for breast cancer risk among postmenopausal women.

Joint effects of nulliparity and other breast cancer risk factors.

BACKGROUND: Pregnancy may reduce breast cancer risk through induction of persistent changes of the mammary gland that make the breast less susceptible to carcinogenic factors. It is not known to what extent the effects of parity are independent of other breast cancer risk factors. METHODS: In a Norwegian cohort of 58 191 women (2890 breast cancers), we assessed whether the effects of parity on postmenopausal breast cancer risk may be modified by menstrual and anthropometric factors. We calculated attributable proportions due to interaction as a measure of synergism. RESULTS: Parity, height, body mass index (BMI), age at menarche and menopause were all associated with breast cancer risk in the expected directions. For BMI, follow-up was stratified into two age groups because of non-proportional hazards. We found that nulliparity and overweight may amplify each other's effect on breast cancer risk among women after 70 years of age (attributable proportion 0.21, 95% confidence interval 0.04-0.39). There was some indication that parity and age at menopause may antagonise each other's effect. Effects of parity were largely unaffected by age at menarche and height. CONCLUSION: Nulliparity and overweight may have a synergistic effect on breast cancer risk in elderly women. If confirmed by others, the findings may help disentangle the interplay of different causes of breast cancer.

Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy.

Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter the expression and function of these drug transporters. Both proteins are present at the main pharmacokinetic barriers including the blood-brain barrier. Data from 291 children with acute lymphoblastic leukaemia were analysed in this retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A genotypes were determined. Encephalopathy episodes were more frequent among those with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5; P=0.03). Patients with the ABCG2 421A allele tended to have more complications than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was similar in those harbouring no or only one of the predisposing genotypes, that is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children suffered encephalopathy in the group with both predisposing genotypes (OR=12.3; P=0.005). In conclusion, these variations exert synergistic effect in predisposing patients to toxic neurological complications of chemotherapy.

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course.

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.

Wine drinking is associated with increased heart rate variability in women with coronary heart disease.

OBJECTIVE: To test the hypothesis that alcohol consumption is positively related to heart rate variability (HRV) in women with coronary heart disease (CHD) and therefore that cardiac autonomic activity is potentially implicated in the mediation of the favourable effects of moderate drinking. DESIGN, SETTINGS, AND PATIENTS: Cross sectional study of female patients who survived hospitalisation for acute myocardial infarction or underwent a revascularisation procedure, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. MAIN OUTCOME MEASURES: Ambulatory 24 hour ECG was recorded during normal activities. The mean of the standard deviations of all normal to normal intervals for all five minute segments of the entire recording (SDNNI) and the following frequency domain parameters were assessed: total power, high frequency power, low frequency power, and very low frequency power. A standardised questionnaire evaluated self reported consumption of individual alcoholic beverage types: beer, wine, and spirits. Other clinical characteristics, such as age, body mass index, smoking habits, history of diabetes mellitus, menopausal status, educational status, and treatment, were also assessed. RESULTS: Wine intake was associated with increased HRV in both time and frequency domains independently of other clinical covariates (for example, ln SDNNI was 3.89 among wine drinkers v 3.59 among wine non-drinkers in the multivariate model; p = 0.014). In contrast, consumption of beer and spirits and the total amount of alcohol consumed did not relate significantly to any of the HRV parameters. CONCLUSION: Intake of wine, but not of spirits or beer, is positively and independently associated with HRV in women with CHD. These results may contribute to the understanding of the complex relation between alcohol consumption and CHD.

Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome.

Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the type of epilepsy most frequently operated on. The predictors for long-term seizure freedom after surgery of TLE-HS are unknown. In this study, we aimed to identify prognostic factors which predict the outcome 6 months and 2, 3 and 5 years after epilepsy surgery of TLE-HS. Our working hypothesis was that the prognostic value of potential predictors depended on the post-operative time interval for which the assessment was made. We included 171 patients (100 females and 71 males, aged 16-59 years) who had undergone presurgical evaluation, including video-EEG, who had had MRI-defined HS, and who had undergone temporal lobectomy. We found that secondarily generalized seizures (SGTCS) and ictal dystonia were associated with a worse 2-year outcome. Both these variables together with older age and longer epilepsy duration were also related to a worse 3-year outcome. Ictal limb dystonia, older age and longer epilepsy duration were associated with long-term surgical failure evaluated 5 years post-operatively. In order to determine the independent predictors of outcomes, we calculated multivariate analyses. The presence of SGTCS and ictal dystonia independently predicted the 2-year outcome. Longer epilepsy duration and ictal dystonia predicted the 3-year outcome. Longer epilepsy duration (P = 0.003) predicted a poor 5-year outcome. Conclusively, predictors for the long-term surgical results of TLE with HS are different from those variables that predict the short-term outcome. Epilepsy duration is the most important predictor for long-term surgical outcome. Our results strongly suggest that surgery for TLE-HS should be performed as early as possible.

Inflammatory markers and heart rate variability in women with coronary heart disease.

PURPOSE: Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive protein (CRP). SUBJECTS AND METHODS: Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay. RESULTS: Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study. CONCLUSION: Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.