N-terminal pro B-type natriuretic peptide levels predict newly detected atrial fibrillation in a population-based cohort

Background B-type natriuretic peptide (BNP) is secreted from cardiomyocytes and may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF). We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with newly detected AF in subjects obtained from the general population. Methods From the PREVEND programme (n=8592), we selected all subjects with an available baseline and four-year electrocardiogram and NTproBNP levels at baseline. We excluded subjects with AF at baseline and subjects with a serum creatinine >2.0 mg/dl. Results In total, 6494 subjects were eligible for the prospective analysis (aged 49±12 years, 49.7% men). At four years, AF was detected in 41 (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7 (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard deviation increment in natural log transformed NT-proBNP was associated with a 54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk factors predisposing to AF. NT-proBNP levels above the sex-specific 80th percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF. Conclusion Plasma levels of NT-proBNP predict newly detected AF in subjects obtained from the general population independent of cardiovascular risk factors predisposing to AF. (Neth Heart J 2008;16:73-8.)     

Predictors of postoperative atrial fibrillation after coronary artery bypass graft surgery

Objectives

The present study was aimed to identify the preoperative, intraoperative, and postoperative predictors of AF in a pure cohort of the patients with coronary artery disease who underwent CABG surgery.

Methods

Between November 2005 and May 2006, 302 consecutive patients were included in this prospective study. All the relevant clinical, electrocardiographic, echocardiographic, and laboratory data were gathered in the included patients and they were also monitored for development of post-CABG AF.

Results

Postoperative AF occurred in 46 (15%) of patients. By univariate analysis, older age, P-wave abnormality in ECG, presence of mitral regurgitation, larger left atrium (LA), left main coronary artery involvement, failure to graft right coronary artery (RCA), and adrenergic use in ICU were significantly associated with occurrence of post-CABG AF (all P< 0.05). However, in the logistic regression model, age (OR: 1.067, 95%CI: 1.02-1.116, P=0.005), LA dimension (OR: 1.102, 95%CI: 1.017-1.1936, P=0.017), P-wave morphology (OR: 12.07, 95%CI: 3.35-48.22, P=0.0001), failure to graft RCA (OR: 3.57, 95%CI: 1.20-10.64, P=0.022), and postoperative adrenergic use (OR: 0.35, 95%CI: 0.13-0.93, P=0.036) remained independently predictive of postoperative AF.

Conclusion

The present study suggested that age, P-wave morphology, LA dimension, failure to graft right coronary artery, and postoperative adrenergic use were independent predictors of post-CABG AF. Therefore, clinical data, ECG and echocardiography may be useful in preoperative risk stratification of the surgical patients for the occurrence of post-CABG AF.     

Increased permeability-oedema and atelectasis in pulmonary dysfunction after trauma and surgery: a prospective cohort study

We have developed a two-step procedure for preparing the skin before peripheral venous catheter (PVC) insertions. This procedure involves two successive swabbings with wipes soaked in alcoholic antiseptic. We investigated whether this two-step procedure was as effective and safe as the standard four-step procedure – washing with detergent, rinsing, drying, applying antiseptic – by carrying out a multicentre randomised equivalence study comparing the frequency of precursor signs of infection at the site of insertion for the two skin preparation procedures. The study was carried out over an eight-month period, and 248 PVC insertion sites were evaluated. The two-step procedure was used for 130 subjects and the standard procedure for 118. Taking into account all the confounding factors predisposing patients to the complications studied, the characteristics of the two groups of patients were found to be similar, with no significant differences noted. The incidence of precursor signs of infection was 11 % 24 hours after PVC insertion (27/248), 25 % at 48 hours (50/203) and at 29 % at 72 hours (34/119). Eleven patients had complications necessitating the withdrawal of the PVC: sensitivity of the insertion site, with redness and/or slight swelling and/or a palpable venous cord. No major complications were observed in this study. The frequency of local complications associated with PVCs reported in this study, whether simple or severe, was not affected by the skin preparation procedure used for PVC insertion (two-step or four-step procedure).     

Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide

The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B-endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS-stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system.     

Lipid levels in midlife and risk of atrial fibrillation over 3 decades—Experience from the Swedish AMORIS cohort: A cohort study

BackgroundThe role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF.Methods and findingsThis population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding.ConclusionsHigh TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk.

Mozhu Ding and colleagues investigate investigate the association between blood lipid levels in midlife and subsequent risk of new-onset atrial fibrillation in Sweden.     

Preoperative evaluation of the cardiac patient for noncardiac surgery.

Perioperative cardiac events continue to represent a significant cause of morbidity in patients undergoing noncardiac surgery. The evaluation of the high risk patient should begin with an assessment of the probability of coronary artery disease and exercise tolerance. Decisions to undergo further evaluation, including noninvasive testing, should be based upon the perioperative morbidity and mortality rate for the planned surgical procedure. In patients with significant coronary artery stenoses and a high probability of perioperative cardiac morbidity, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and preoperative optimization of hemodynamics in an intensive care unit have all been advocated as means of reducing risk.     

Plasma atrial natriuretic peptide and cyclic nucleotide levels before and after a marathon

Plasma alpha-atrial natriuretic peptide (alpha-ANP) concentration and levels of cyclic nucleotides [guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP)] were studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (base line), at 3 P.M. (i.e., 2 h before the start), on arrival, and 12 and 36 h and 7 days later. Compared with the base-line values of plasma alpha-ANP (5 pmol/l), cGMP (3.8 nmol/l), and cAMP (15.8 nmol/l), the plasma levels of alpha-ANP, cGMP, and cAMP were increased immediately after the marathon, respectively, to 12.0 pmol/l, 12.7 nmol/l, and 50.5 nmol/l. The increase in the plasma alpha-ANP concentration was related (r = 0.85; P less than 0.001) to the changes in plasma cGMP, plasma lactate, hematocrit, and body weight. The plasma cGMP and cAMP concentrations had returned to the prerace levels 12 h after the marathon, whereas the plasma alpha-ANP concentration was significantly lower (3.1 pmol/l) than the base-line values and increased above the prerace values 36 h (7.5 pmol/l) and 7 days (6.8 pmol/l) after the marathon. The plasma cGMP level was also higher 36 h (5.4 nmol/l) and 7 days (5.0 nmol/l) after the marathon race.     

High incidence of unplanned pregnancy after antiretroviral therapy initiation: findings from a prospective cohort study in South Africa

Background

Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.

Methods

Non-pregnant women ages 18–35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009–March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants'' routine ART clinic visits.

Findings

Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5–25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1–2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4–34.1], 15.9% [12.0–20.8], and 21.0% [16.8–26.1] for women on ART 0–1 yr, >1 yr–2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2–8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.

Conclusions

Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted.     

Stress and survival after cancer: a prospective study of a Finnish population-based cohort

Stress has been suggested to reduce survival after cancer, but the results of previous studies have been contradictory. We investigated the hypothesis in a national cohort of adults in Finland. Of those who completed the Stressful Life Events scale and the Stress of Daily Activities scale, 1470 and 1882, respectively, later had cancer and were included in the analysis, covering 23 years of follow-up between 1982 and 2004. In Cox regression analysis, the multivariate hazard ratio (HR) was 0.99 (95% confidence interval [CI], 0.96-1.01) for total number of life events and the HR for the life change score was 0.99 (95% CI, 0.95-1.03). Further, the HR was 0.92 (95% CI, 0.69-1.22) for severe daily stress. Overall, the results of the current study do not support the hypothesis that stress reduces cancer survival.     

Rheumatic symptoms after cardiac surgery: a prospective study.

The incidence of different types of shoulder pain after open heart surgery was studied prospectively. Of 101 patients studied, 45 developed rheumatic symptoms during the first six weeks after the operation. Thirty eight patients reported pain in the region of the shoulder girdle with no loss of shoulder function (postpericardiotomy rheumatism). Three of these patients also had features compatible with the postpericardiotomy syndrome (fever, malaise, or pleuritic chest pain), and seven developed the syndrome without pain in the shoulder girdle. Of these 10 patients, one had generalised myalgia. Postpericardiotomy rheumatism alone was not associated with increased inflammation (measured by the erythrocyte sedimentation rate and concentration of C reactive protein); immunological tests including measurement of antibodies to cardiac muscle yielded inconclusive results. Replies to a postal questionnaire showed that symptoms of postpericardiotomy rheumatism were present for over three months in 18 patients and for six months or longer in 14. In view of the large number of patients now having open heart surgery postpericardiotomy rheumatism should be considered when patients report pain around the shoulders so that it is not misdiagnosed as angina.     

Assessment of risk factors for postoperative cognitive dysfunction after coronary artery bypass surgery: a single-center retrospective cohort study

Aim: To find out risk factors for postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG), and to provide basis for clinical prevention of POCD. A total of 88 patients who underwent CABG were surveyed with Telephone Questionnaire (TICS-M) for their cognitive impairment after 3, 7, 21, 90, 180 days post-surgery. The occurrence of POCD was diagnosed by Neuropsychological Battery which included Vocabular Learning Test (VLT), Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Symbol Digit Modalities Test (SDMT). The preoperative, intraoperative and postoperative risk factors were assessed by the χ² or t test. Multivariate analysis was used to study the correlation between the risk factors and the occurrence of POCD. Age, aortic plaque, carotid artery stenosis, cerebrovascular disease, anesthesia time, the rate of decline in intraoperative hemoglobin concentration (ΔHb) and systemic inflammatory response syndrome (SIRS) score on postoperative day 2 had statistically significant (P<0.05) influence on the occurrence of POCD. Aortic plaque, carotid artery stenosis, anesthesia time and SIRS score (odds ratio (OR) value > 1, P<0.05) are the risk factors for POCD. The incidence of day-21 and -180 POCD was approximately 26.1 and 22.7%, respectively.     

Prevalence of and risk factors for persistent postoperative nonanginal pain after cardiac surgery: a 2-year prospective multicentre study

Background:

Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.

Methods:

We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.

Results:

A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.

Interpretation:

Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.Postoperative pain that persists beyond the normal time for tissue healing (> 3 mo) is increasingly recognized as an important complication after various types of surgery and can have serious consequences on patients’ daily living.^1–3 Cardiac surgeries, such as coronary artery bypass grafting (CABG) and valve replacement, rank among the most frequently performed interventions worldwide.⁴ They aim to improve survival and quality of life by reducing symptoms, including anginal pain. However, persistent postoperative pain of nonanginal origin has been reported in 7% to 60% of patients following these surgeries.^5–23 Such variability is common in other types of major surgery and is due mainly to differences in the definition of persistent postoperative pain, study design, data collection methods and duration of follow-up.^1–3,24Few prospective cohort studies have examined the exact time course of persistent postoperative pain after cardiac surgery, and follow-up has always been limited to a year or less.^9,14,25 Factors that put patients at risk of this type of problem are poorly understood.²⁶ Studies have reported inconsistent results regarding the contribution of age, sex, body mass index, preoperative angina, surgical technique, grafting site, postoperative complications or level of opioid consumption after surgery.^{5–7,9,13,14,16–19,21–23,25,27} Only 1 study investigated the role of chronic nonanginal pain before surgery as a contributing factor;²¹ 5 others prospectively assessed the association between persistent postoperative pain and acute pain intensity in the first postoperative week but reported conflicting results.^{13,14,21,22,25} All of the above studies were carried out in a single hospital and included relatively small samples. None of the studies examined the contribution of psychological factors such as levels of anxiety and depression before cardiac surgery, although these factors have been shown to influence acute or persistent postoperative pain in other types of surgery.^1,24,28,29We conducted a prospective multicentre cohort study (the CARD-PAIN study) to determine the prevalence of persistent postoperative pain of nonanginal origin up to 24 months after cardiac surgery and to identify risk factors for the presence and severity of the condition.     

Radioimmunoassay of atrial natriuretic factor: Human plasma levels

A simple and sensitive radioimmunoassay procedure has been developed for the determination of atrial natriuretic factor (ANF) in human plasma. The rabbit antiserum was obtained from a commercial source. ANF was extracted from plasma using an octadecasilyl silica cartridge with a recovery of 78.7%. HPLC of the plasma extract showed the presence of one immunoreactive peak of ANF correponding to its low molecular weight form. Plasma ANF in humans increased from 8.0 ± 2.2 in upright position to 20.0 ± 5.9 fmol/ml (n = 6) in downward position (p < 0.005).     

Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study

BACKGROUND: Metronidazole is an important antibacterial agent commonly used in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The objective was to examine the fetal safety of metronidazole. METHODS: The Israeli Teratogen Information Service prospectively collected and followed up 228 women exposed to metronidazole in pregnancy, 86.2% of whom with first-trimester exposure. Pregnancy outcome was compared with that of a control group, who were counseled during the same period for nonteratogenic exposure. RESULTS: There was no difference in the rate of major malformations between the groups (3/190; 1.6% [metronidazole] vs. 8/575; 1.4% [control], P = 0.739). The rate of major malformations did not differ between the groups even after including elective terminations of pregnancy due to prenatally diagnosed malformations (5/192; 2.6% [metronidazole] vs. 12/579; 2.1% [control], P = 0.777). A reduced neonatal birth weight was found in the metronidazole group compared with controls without significant differences in the rate of prematurity or in gestational age at delivery. The mean birth weight was lower in the metronidazole group when comparing the subgroup of term infants. CONCLUSIONS: This study confirms that metronidazole does not represent a major teratogenic risk in humans when used in the recommended doses.     

Effects of atrial natriuretic peptides and furosemide in conscious dogs

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.     

Human oocyte morphometry before and after cryopreservation: A prospective cohort study

The cryopreservation of human oocytes is an important strategy to spare fertility in women submitted to gonadotoxic therapy, ovarian surgery, or even to allow gestation by assisted reproduction technology after natural ovarian senescence. Methods to predict oocyte resistance to cryopreservation are still based on qualitative morphological assessment. In this study we evaluated whether morphometric characteristics of mature oocytes before vitrification and after warming are related to successful fertilization by intracytoplasmic sperm injection (ICSI). This was a prospective cohort study including 28 infertile women and 71 oocytes. Morphometric assessments included oocyte diameter, perivitelline space (PS), zona pellucida (ZP) and first polar body (PB). Out of 49 warmed oocytes, 27 (55%) survived cryopreservation and their pre-vitrification measures were similar to those of the 22 oocytes that perished. However, the oocytes that eventually failed to be fertilized had undergone more enlargement of the total diameter (p = 0.029) and shrinking of the PS (p = 0.033) after cryopreservation, compared to oocytes that were successfully fertilized. These findings suggest that the morphometric characteristics of fresh oocytes do not predict their survival to vitrification, while fertilization failure is associated with oocyte enlargement and PS shrinking after cryopreservation.     

Preoperative detection of the postoperative risk thromboembolism. Results of a prospective study. IV. Thrombocyte parameters

Some platelet properties determined preoperatively in the course of a prospective clinical study show significant differences between the patient groups with and without DVT after total hip replacement. None of the platelet tests alone is indicative of the development of DVT.