Circulating levels of C-reactive protein (CRP) are associated with an increased risk of coronary artery disease (CAD), stroke, and peripheral artery disease (PAD). Observational and experimental ...evidence suggest that CRP might differentially predict fatal and nonfatal cardiovascular events. Here, we sought to determine the predictive value of CRP for fatal and nonfatal CAD, stroke, or PAD.
CRP levels were measured in 18 450 apparently healthy participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Cox proportional hazards models were used to quantify the association between CRP levels and fatal and nonfatal CAD events, strokes, and PAD events. Bootstrapping was applied to test for significant differences between the risk of fatal and nonfatal events. During 208 485 person-years at risk, 2915 CAD events, 361 strokes, and 657 PAD events occurred. CRP was associated with fatal and nonfatal CAD events and nonfatal PAD events. When adding CRP to predictive risk models for fatal and nonfatal events corrected for known cardiovascular risk factors, the net reclassification index was 2.1% for fatal and 1.9% for nonfatal events. Multivariate adjusted hazard ratios for fatal CAD events (hazard ratio, 1.36; 95% confidence interval, 1.27-1.46) differed significantly (mean difference, 13%; 95% confidence interval, 5.1%-21.9%; P<0.001) from the multivariate adjusted hazard ratio for nonfatal CAD events (hazard ratio, 1.21; 95% confidence interval, 1.15-1.26).
In the EPIC-Norfolk cohort, CRP was associated with fatal and nonfatal CAD events, as well as nonfatal PAD events. Adding CRP to risk stratification models resulted in a small improvement in classification for both fatal and nonfatal events. Importantly, CRP was significantly more strongly associated with fatal CAD events than with nonfatal CAD events.
Background
C‐reactive protein (CRP) is a well‐documented predictor of cardiovascular diseases and mortality. We aimed to better understand the distribution and determinants of CRP in the population.
...Materials and methods
Study participants were men and women aged 40–79 in the UK‐based EPIC‐Norfolk population‐based cohort study. CRP was measured in 18 586 available serum samples (8334 men and 10 252 women) and remeasured in 6087 individuals on average 13 years later using a high‐sensitivity assay.
Results
In cross‐sectional analyses, the range of serum CRP was 0·1–188·3 mg/L and the median 1·6 mg/L. A third of the population had serum CRP levels above 3 mg/L. Serum CRP levels were comparable in men and women who were not taking postmenopausal hormone replacement therapy (HRT). Women who were taking HRT had double CRP levels compared with HRT nonusers. Smoking was also strongly related to CRP in men and women. Serum CRP was positively and independently associated with age, body mass index and waist circumference and inversely with height. A stronger association with serum CRP measured concurrently than on average 13 years later indicated a short‐term rather than long‐term association with smoking and HRT use. Social class and alcohol intake were not independently related to CRP, but there was a strong inverse association with educational status.
Conclusion
The distribution of serum CRP in the population is similar in men and women after taking into account smoking and HRT use. Anthropometric factors as well as educational status are strongly related to serum CRP.
Rationale, aims and objectives Knowledge in evidence‐based medicine (EBM) is increasingly becoming a core competence in medical education. We evaluated the trainee doctors’ attitudes and knowledge ...of EBM to obtain the basis required for developing appropriate teaching and learning opportunities.
Methods Trainee physicians at a Tehran University hospital were surveyed. The questionnaire included six questions evaluating knowledge of EBM, the number of correct answers yielding the knowledge score, and eight questions evaluating attitudes towards EBM. Participants were also asked to mark on a 10‐cm Visual Analogue Scale their use of various information sources and tendency to participate in EBM training courses.
Results The response rate was 80% (104/130). The mean knowledge score was 3 ± 1.3 (SD) on a range of 0–6 for all respondents and was not significantly different between interns (2.9 ± 1.4) and postgraduates (3.3 ± 1.0). Forty one per cent of interns and 66% of postgraduates had a positive attitude towards EBM; the remaining respondents were neutral. Textbooks and consulting experts were the most, and Cochrane Library was the least, used sources of information among both interns and postgraduates. The knowledge score was not associated with attitude, but was higher in those with previous research experience, prior EBM training, or the postgraduates that read more articles. The postgraduates and those with prior EBM training showed a significantly more positive attitude towards EBM.
Conclusion The present study demonstrates that the majority of trainee physicians at a Tehran University hospital lack adequate knowledge about basic concepts of EBM. Furthermore, most of them continue to use traditional sources of knowledge rather than evidence‐based sources. On the positive side, there was an overall positive attitude towards EBM and the majority had a positive tendency to take part in EBM training courses.
Background
Practice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challenge in clinical and research settings. However, an attenuated practice effect ...may indicate the presence of brain pathologies. This study aimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, and their associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in the CHARIOT-PRO SubStudy.
Materials and Methods
502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinic visits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scores in total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjusting for age, sex, education level,
APOE
-ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors for amyloid positivity status based on defined thresholds, using logistic regression.
Results
Participants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test than in the initial test (Cohen’s d
z
= 0.48, 0.70 and 0.35,
P
< 0.001). On the immediate memory index, the PE was significantly lower in the amyloid positive group than the amyloid negative group (
P
= 0.022). Older participants (≥70 years), women, non-
APOE
-ε4 carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRI parameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictors for amyloid positivity (
P
< 0.05).
Conclusion
Significant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired older adults. The association with amyloid status suggests that practice effects are not simply a source of measurement error but may be informative with regard to underlying neuropathology.
Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the ...European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk.
We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models.
7574 participants (5233 69·1% men, 2341 30·9% women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 72·3% men and 399 27·7% women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 95% CI 0·000 to 0·008 for SCORE; from 0·699 to 0·700, change 0·001 0·000 to 0·003 for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 95% CI -97 to -13 for SCORE; from 14 739 to 14 729, change -10 -28 to 7 for ASCVD), and the continuous net reclassification index (0·353 95% CI 0·234 to 0·447 for SCORE; 0·232 0·030 to 0·344 for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements.
Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions.
UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging.
Several studies have assessed the impact of COVID-19-related lockdowns on sleep quality across global populations. However, no study to date has specifically assessed
populations, particularly those ...at highest risk of complications from coronavirus infection deemed "clinically-extremely-vulnerable-(COVID-19CEV)" (as defined by Public Health England).
In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio-demographic factors. We examined associations between these variables and sleep quality; and explored interactions of COVID-19CEV status with significant predictors of poor sleep, to identify potential moderating factors.
Thirty-seven percent of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep.
Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a "clinically-extremely-vulnerable" population and the sex differences identified within this group. Male and female older adults deemed COVID-19CEV may benefit from targeted mental health and dietary interventions, respectively. This work extends the available evidence on the notable impact of lack of social interactions during the COVID-19 pandemic on sleep, and provides recommendations toward areas for future work, including research into vulnerability factors impacting sleep disruption and COVID-19-related complications. Study results may inform tailored interventions targeted at modifiable risk factors to promote optimal sleep; additionally, providing empirical data to support health policy development in this area.
Clinical guidelines suggest preventive interventions such as statin therapy for individuals with a high estimated 10-year risk of major cardiovascular events. For those with a low or intermediate ...estimated risk, risk-factor screenings are recommended at 5-year intervals; this interval is based on expert opinion rather than on direct research evidence. Using longitudinal data on the progression of cardiovascular disease risk over time, we compared different screening intervals in terms of timely detection of high-risk individuals, cardiovascular events prevented, and health-care costs.
We used data from participants in the British Whitehall II study (aged 40–64 years at baseline) who had repeated biomedical screenings at 5-year intervals and linked these data to electronic health records between baseline (Aug 7, 1991, to May 10, 1993) and June 30, 2015. We estimated participants' 10-year risk of a major cardiovascular event (myocardial infarction, cardiac death, and fatal or non-fatal stroke) using the revised Atherosclerotic Cardiovascular Disease (ASCVD) calculator. We used multistate Markov modelling to estimate optimum screening intervals on the basis of progression rates from low-risk and intermediate-risk categories to the high-risk category (ie, ≥7·5% 10-year risk of a major cardiovascular event). Our assessment criteria included person-years spent in a high-risk category before detection, the number of major cardiovascular events prevented and quality-adjusted life-years (QALYs) gained, and screening costs.
Of 6964 participants (mean age 50·0 years SD 6·0 at baseline) with 152 700 person-years of follow-up (mean follow-up 22·0 years SD 5·0), 1686 participants progressed to the high-risk category and 617 had a major cardiovascular event. With the 5-year screening intervals, participants spent 7866 (95% CI 7130–8658) person-years unrecognised in the high-risk group. For individuals in the low, intermediate-low, and intermediate-high risk categories, 21 alternative risk category-based screening intervals outperformed the 5-yearly screening protocol. Screening intervals at 7 years, 4 years, and 1 year for those in the low, intermediate-low, and intermediate-high-risk category would reduce the number of person-years spent unrecognised in the high-risk group by 62% (95% CI 57–66; 4894 person-years), reduce the number of major cardiovascular events by 8% (7–9; 49 events), and raise 44 QALYs (40–49) for the study population.
In terms of timely preventive interventions, the 5-year screening intervals were unnecessarily frequent for low-risk individuals and insufficiently frequent for intermediate-risk individuals. Screening intervals based on risk-category-specific progression rates would perform better in terms of preventing major cardiovascular disease events and improving cost-effectiveness.
Medical Research Council, British Heart Association, National Institutes on Aging, NordForsk, Academy of Finland.
Chronic obstructive pulmonary disease is known to be associated with systemic inflammation. We examined the longitudinal association of C-reactive protein (CRP) and lung function in a cohort of ...18,110 men and women from the European Prospective Investigation Into Cancer in Norfolk who were 40-79 years of age at baseline (recruited in 1993-1997) and followed-up through 2011. We assessed lung function by measuring forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at baseline, 4 years, and 13 years. Serum CRP levels were measured using a high-sensitivity assay at baseline and the 13-year follow up. Cross-sectional and longitudinal associations of loge-CRP and lung function were examined using multivariable linear mixed models. In the cross-sectional analysis, 1-standard-deviation increase in baseline loge-CRP (about 3-fold higher CRP on the original milligrams per liter scale) was associated with a -86.3 mL (95% confidence interval: -93.9, -78.6) reduction in FEV1. In longitudinal analysis, a 1-standard-deviation increase in loge-CRP over 13 years was also associated with a -64.0 mL (95% confidence interval: -72.1, -55.8) decline in FEV1 over the same period. The associations were similar for FVC and persisted among lifetime never-smokers. Baseline CRP levels were not predictive of the rate of change in FEV1 or FVC over time. In the present study, we found longitudinal observational evidence that suggested that increases in systemic inflammation are associated with declines in lung function.
Background: About 30% of women experience severe continuous low‐back pain in labour, but limited options are available to reduce this pain especially in developing countries and remote areas.
Aims: ...To evaluate the efficacy of subcutaneous sterile water injection in reduction of labour pain compared with placebo.
Methods: One hundred (100) consecutive patients were enrolled in a double‐blind randomised controlled trial. During the first stage of labour with planned normal vaginal delivery, the intervention group (n = 50) received 0.5 mL sterile water injected subcutaneously and the control group (n = 50) received normal saline as a placebo. Pain score was measured before and 10 and 45 min after the injection, using the faces rating scale.
Main outcome measure: Low‐back labour pain.
Results: The two groups were not significantly different regarding maternal age and weight, gestational age, parity and gravidity and degree of effacement. The median pain score was equal in both groups prior to the injection. Pain severity was reduced in both groups after the injection. However, the median pain score in the sterile water group was significantly lower than the placebo group 10 min (P < 0.01), as well as 45 min, after the injection (P < 0.01).
Conclusion: Administering one subcutaneous injection of sterile water in a painful point of the lumbosacral area is effective in reducing low‐back pain during labour.
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