Sex Differences in Mortality Risk after the First Hospitalisation with Lower Extremity Peripheral Arterial Disease.

OBJECTIVE: Lower extremity peripheral arterial disease (PAD) is a severe condition that increases the risk of major adverse cardiovascular events, major adverse limb events, and all cause mortality. This study aimed to investigate the mortality risk among females and males hospitalised for the first time with lower extremity PAD. METHODS: Three cohorts of patients who were admitted for the first time with lower extremity PAD in 2007 - 2010, 2011 - 2014, and 2015 - 2018 were constructed. For the 2007 - 2010 and 2011 - 2014 cohorts, the 28 day, one year, and five year mortality rates were calculated, assessing survival time from date of hospital admission until date of death, end of study period, or censoring. For the 2015 - 2018 cohort, only 28 day and one year mortality were investigated due to lack of follow up data. Mortality rates of these cohorts were compared with the general population using standardised mortality rates (SMRs), and the risk of death between sexes was evaluated using Cox proportional hazards models. Cox models were adjusted for age, cardiovascular disease, and diabetes mellitus to account for potential confounding factors. RESULTS: In total, 7 950, 9 670, and 13 522 patients were included in the 2007 - 2010, 2011 - 2014, and 2015 - 2018 cohorts, respectively. Over 60% of individuals in each cohort were males. Mortality rates at 28 day and one year remained stable across all cohorts, while the five year mortality rate increased for both males and females in the 2011 - 2014 cohort. The SMRs both of females and males with PAD were significantly higher than in the general population. Multivariable regression analyses found no significant differences in mortality risk between sexes at 28 day and one year. However, the five year mortality risk was lower in females, with a hazard ratio of 0.89 (95% confidence interval [CI] 0.83 - 0.97) in the 2007 - 2010 cohort and 0.88 (95% CI 0.82 - 0.94) in the 2011 - 2014 cohort. CONCLUSION: The five year mortality risk has increased, and females face a lower mortality risk than males. Lower extremity PAD still carries unfavourable long term consequences compared with the general population.

Non-specific effects of the inactivated influenza vaccine. A test-negative study: The inactivated influenza vaccine and SARS-CoV-2 infections.

BACKGROUND: Previous research suggested that the inactivated influenza vaccine (IIV) may protect against SARS-CoV-2 infection or a severe course of COVID-19. These findings were however based on cohort studies, that are prone to confounding by indication. We examined the association between IIV and SARS-Cov-2 infection in a Dutch population using a test-negative design. METHODS: This test-negative case-control study was conducted in adults (≥60) who tested because of COVID-19 like symptoms at community SARS-CoV-2 testing locations in the Netherlands during the period of November 8th 2021-March 11th 2022. Information on receipt of IIV in October-November 2021 was routinely collected at each visit. Logistic regression was used to calculate unadjusted, partially (sex, age, education level) and fully adjusted (COVID-19 vaccination, IIV 2020) odds ratios (ORs) for receipt of IIV in SARS-CoV-2 positive versus negative subjects. Differential effects on SARS-CoV-2 risk by time since IIV were investigated by including an interaction term for calendar time: November 2021-January 2022 vs February-March 2022. RESULTS: In total, 1,832 participants were included in the main analysis, of whom 336 (18.3 %) had a positive SARS-CoV-2 test. No significant association between IIV and SARS-CoV-2 infection was found; fully adjusted OR of 1.07 (95 % CI: 0.78-1.49). The interaction term for time periods was not significant (1.04 [95 % CI: 0.51-2.15], p = 0.91). Results were robust in sensitivity analyses. CONCLUSIONS: While earlier observational studies suggested a protective non-specific effect of IIV and SARS-CoV-2 infections, this smaller, but well controlled test-negative design study does not suggest an effect, either positive or negative. Larger test-negative design studies, or alternative designs such as the self-controlled case series design are needed to confirm these findings and provide more definite answers on the topic.

Sex differences in the intensity of statin prescriptions at initiation in a primary care setting.

BACKGROUND: Current guidelines for the prevention and management of cardiovascular diseases (CVD) provide similar recommendations for the use of statins in both women and men. In this study, we assessed sex differences in the intensity of statin prescriptions at initiation and in the achievement of treatment targets, among individuals without and with CVD, in a primary care setting. METHODS: Electronic health record data from statin users were extracted from the PHARMO Data Network. Poisson regressions were used to investigate sex differences in statin intensity and in the achievement of treatment targets. Analyses were stratified by age group, disease status and/or CVD risk category. RESULTS: We included 82 714 individuals (46% women) aged 40-99 years old. In both sexes, the proportion of individuals with a dispensed prescription for high-intensity statin at initiation increased between 2011 and 2020. Women were less likely to be prescribed high-intensity statins as compared with men, both in the subgroups without a history of CVD (risk ratio (RR) 0.69 (95% CI: 0.63 to 0.75)) and with CVD (RR 0.77 (95% CI: 0.74 to 0.81)). Women were less likely than men to achieve target levels of low-density lipoprotein cholesterol following statin initiation in the subgroup without CVD (RR 0.98 (95% CI: 0.97 to 1.00)) and with a history of CVD (RR 0.94 (95% CI: 0.89 to 0.98)). CONCLUSION: Compared with men, women were less likely to be prescribed high-intensity statins at initiation and to achieve treatment targets, both in people without and with a history of CVD, and independent of differences in other individual and clinical characteristics.

Sex Differences in the Primary Prevention of Cardiovascular Diseases in a Dutch Primary Care Setting.

Background: Sex differences in the primary prevention of cardiovascular diseases (CVD) have been shown, but the evidence is mixed and fragmented. In this study, we assessed sex differences in cardiovascular risk factors assessment, risk factor levels, treatment, and meeting of treatment targets, within a Dutch primary care setting. Methods: Data were obtained from individuals aged 40 to 70 years old, without prior CVD, registered during the entire year in 2018 at one of the 51 general practices participating in the Julius General Practitioner's Network (JGPN). History of CVD was defined based on the International Classification of Primary Care (ICPC). Linear and Poisson regressions were used to investigate sex differences in risk factor assessment, risk factor levels, treatment, and meeting of treatment targets. Results: We included 83,903 individuals (50% women). With the exception of glycated hemoglobin (HbA1c), all risk factors for CVD were more often measured in women than in men. Lipid measurements and body mass index values were higher in women, while blood pressure (BP) and HbA1c levels were higher in men, along with estimated glomerular filtration rate (eGFR) levels. Among individuals with elevated BP or cholesterol levels, no sex difference was observed in the prescription of antihypertensive medications (RR 1.00, 95% CI: 0.94-1.06) but women were less likely than men to receive lipid-lowering medications (RR 0.87, 95% CI: 0.79-0.95). Among treated individuals, women were more likely than men to meet adequate levels of blood pressure (RR 1.17, 95% CI: 1.09-1.25) and less likely to meet target levels of cholesterol (RR 0.90, 95% CI: 0.83-0.98). Conclusion: While women were more likely to have their CVD risk factors measured, they were less likely to be prescribed lipid-lowering medications and to meet target levels. When treated, men were less likely to achieve adequate blood pressure control.

Ventilation and thermal conditions in secondary schools in the Netherlands: Effects of COVID-19 pandemic control and prevention measures.

During the COVID-19 pandemic, the importance of ventilation was widely stressed and new protocols of ventilation were implemented in school buildings worldwide. In the Netherlands, schools were recommended to keep the windows and doors open, and after a national lockdown more stringent measures such as reduction of occupancy were introduced. In this study, the actual effects of such measures on ventilation and thermal conditions were investigated in 31 classrooms of 11 Dutch secondary schools, by monitoring the indoor and outdoor CO2 concentration and air temperature, both before and after the lockdown. Ventilation rates were calculated using the steady-state method. Pre-lockdown, with an average occupancy of 17 students, in 42% of the classrooms the CO2 concentration exceeded the upper limit of the Dutch national guidelines (800 ppm above outdoors), while 13% had a ventilation rate per person (VRp) lower than the minimum requirement (6 l/s/p). Post-lockdown, the indoor CO2 concentration decreased significantly while for ventilation rates significant increase was only found in VRp, mainly caused by the decrease in occupancy (average 10 students). The total ventilation rate per classrooms, mainly induced by opening windows and doors, did not change significantly. Meanwhile, according to the Dutch national guidelines, thermal conditions in the classrooms were not satisfying, both pre- and post-lockdown. While opening windows and doors cannot achieve the required indoor environmental quality at all times, reducing occupancy might not be feasible for immediate implementation. Hence, more controllable and flexible ways for improving indoor air quality and thermal comfort in classrooms are needed.

The Frequency of Primary Healthcare Contacts Preceding the Diagnosis of Lower-Extremity Arterial Disease: Do Women Consult General Practice Differently?

Background. Women with lower-extremity arterial disease (LEAD) are often underdiagnosed, present themselves with more advanced disease at diagnosis, and fare worse than men. Objective. To investigate to what extent potential gender differences exist in the frequency and reasons for general practitioner (GP) consultation six months prior to the diagnosis of LEAD, as potential indicators of diagnostic delay. Methods. Individuals older than 18 years diagnosed with LEAD, sampled from the Julius General Practitioner's Network (JGPN), were included and compared with a reference population, matched (1:2.6 ratio) in terms of age, sex, and general practice. We applied a zero-inflated negative binomial (ZINB) regression model. Results. The study population comprised 4044 patients with LEAD (43.5% women) and 10,486 subjects in the reference population (46.3% women). In the LEAD cohort, the number of GP contacts was 2.70 (95% CI: 2.42, 3.02) in women and 2.54 (2.29, 2.82) in men. In the reference cohort, 1.77 (95% CI: 1.62, 1.94) in women and 1.63 (95% CI: 1.50, 1.78) in men. In the LEAD cohort, 21.9% of GP contacts occurred one month prior to diagnosis. In both cohorts and both sexes, the most common cause of consultation during the last month before the index date was cardiovascular problems. Conclusions. Six months preceding the initial diagnosis of LEAD, patients visit the GP more often than a similar population without LEAD, regardless of gender. Reported gender differences in the severity of LEAD at diagnosis do not seem to be explained by a delay in presentation to the GP.

Screening for abdominal aortic aneurysm in patients with clinically manifest vascular disease.

AIMS: Declining prevalence of abdominal aortic aneurysm (AAA) might force a more targeted screening approach (high-risk populations only) in order to maintain (cost-)effectiveness. We aimed to determine temporal changes in the prevalence of screening-detected AAA, to assess AAA-related surgery, and evaluate all-cause mortality in patients with manifest vascular disease. METHODS AND RESULTS: We included patients with manifest vascular disease but without a history of AAA enrolled in the ongoing single-centre prospective UCC-SMART cohort study. Patients were screened at baseline for AAA by abdominal ultrasonography. We calculated sex- and age-specific prevalence of AAA, probability of survival in relation to the presence of AAA, and the proportion of patients undergoing AAA-related surgery. Prevalence of screening-detected AAA in 5440 screened men was 2.5% [95% confidence interval (CI) 2.1-2.9%] and in 1983 screened women 0.7% (95% CI 0.4-1.1%). Prevalence declined from 1997 until 2017 in men aged 70-79 years from 8.1% to 3.2% and in men aged 60-69 years from 5.7% to 1.0%. 36% of patients with screening-detected AAA received elective AAA-related surgery during follow-up (median time until surgery = 5.3 years, interquartile range 2.5-9.1). Patients with screening-detected AAA had a lower probability of survival (sex and age adjusted) compared to patients without screening-detected AAA (51%, 95% CI 41-64% vs. 69%, 95% CI 68-71%) after 15 years of follow-up. CONCLUSION: The prevalence of screening-detected AAA has declined over the period 1997-2017 in men with vascular disease but exceeds prevalence in already established screening programs targeting 65-year-old men. Screening for AAA in patients with vascular disease may be cost-effective, but this remains to be determined.

Heart failure with preserved, mid-range, and reduced ejection fraction across health care settings: an observational study.

AIMS: This study aimed to assess the sex-specific distribution of heart failure (HF) with preserved, mid-range, and reduced ejection fraction across three health care settings. METHODS AND RESULTS: In this descriptive observational study, we retrieved the distribution of HF types [with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF)] for men and women between 65 and 79 years of age in three health care settings from a single country: (i) patients with screening-detected HF in the high-risk community (i.e. those with shortness of breath, frailty, diabetes mellitus, and chronic obstructive pulmonary disease) from four screening studies, (ii) patients with confirmed HF from primary care derived from a single observational study, and (iii) patients with confirmed HF from outpatient cardiology clinics participating in a registry. Among 1407 patients from the high-risk community, 288 had screen-detected HF (15% HFrEF, 12% HFmrEF, 74% HFpEF), and 51% of the screen-detected HF patients were women. In both women (82%) and men (65%), HFpEF was the most prevalent HF type. In the routine general practice population (30 practices, 70 000 individuals), among the 160 confirmed HF cases, 35% had HFrEF, 23% HFmrEF, and 43% HFpEF, and in total, 43% were women. In women, HFpEF was the most prevalent HF type (52%), while in men, this was HFrEF (41%). In outpatient cardiology clinics (n = 34), of the 4742 HF patients (66% HFrEF, 15% HFmrEF, 20% HFpEF), 36% were women. In both women (56%) and men (71%), HFrEF was the most prevalent HF type. CONCLUSIONS: Both HF types and sex distribution vary considerably in HF patients of 65-79 years of age among health care settings. From the high-risk community through to general practice to the cardiology outpatient setting, there is a shift in HF type from HFpEF to HFrEF and a decrease in the proportion of HF patients that are women.

Blood pressure and cholesterol measurements in primary care: cross-sectional analyses in a dynamic cohort.

BACKGROUND: Guidelines on cardiovascular risk management (CVRM) recommend blood pressure (BP) and cholesterol measurements every 5 years in men aged ≥40 years and (post-menopausal) women aged ≥50 years. AIM: To evaluate CVRM guideline implementation. DESIGN & SETTING: Cross-sectional analyses in a dynamic cohort using primary care electronic health record (EHR) data from the Julius General Practitioners' Network (JGPN) (n = 388 929). METHOD: Trends (2008-2018) were assessed in the proportion of patients with at least one measurement (BP and cholesterol) every 1, 2, and 5 years, in those with:1. a history of cardiovascular disease (CVD) and diabetes mellitus (DM);2. a history of DM only;3. a history of CVD only;4. a cardiovascular risk assessment (CRA) indication based on other medical history, or;5. no CRA indication.Trends were evaluated over time using logistic regression mixed-model analyses. RESULTS: Trends in annual BP and cholesterol measurement increased for patients with a history of CVD from 37.0% to 48.4% (P<0.001) and 25.8% to 40.2% (P<0.001). In the 5-year window from 2014-2018, BP and cholesterol measurements were performed respectively in 78.5% and 74.1% of all men aged ≥40 years and 82.2% and 78.5% of all women aged ≥50 years. Least measured were patients without a CRA indication (men 60.2% and 62.4%; women 55.5% and 59.3%). CONCLUSION: The fairly high frequency of CVRM measurements available in the EHR of patients in primary care suggests an adequate implementation of the CVRM guideline. As nearly all individuals visit the GP at least once within a 5-year time window, improvement of CVRM remains possible, especially in those without a CRA indication.

Data mining to retrieve smoking status from electronic health records in general practice.

Aims: Optimize and assess the performance of an existing data mining algorithm for smoking status from hospital electronic health records (EHRs) in general practice EHRs. Methods and results: We optimized an existing algorithm in a training set containing all clinical notes from 498 individuals (75 712 contact moments) from the Julius General Practitioners' Network (JGPN). Each moment was classified as either 'current smoker', 'former smoker', 'never smoker', or 'no information'. As a reference, we manually reviewed EHRs. Algorithm performance was assessed in an independent test set (n = 494, 78 129 moments) using precision, recall, and F1-score. Test set algorithm performance for 'current smoker' was precision 79.7%, recall 78.3%, and F1-score 0.79. For former smoker, it was precision 73.8%, recall 64.0%, and F1-score 0.69. For never smoker, it was precision 92.0%, recall 74.9%, and F1-score 0.83. On a patient level, performance for ever smoker (current and former smoker combined) was precision 87.9%, recall 94.7%, and F1-score 0.91. For never smoker, it was 98.0, 82.0, and 0.89%, respectively. We found a more narrative writing style in general practice than in hospital EHRs. Conclusion: Data mining can successfully retrieve smoking status information from general practice clinical notes with a good performance for classifying ever and never smokers. Differences between general practice and hospital EHRs call for optimization of data mining algorithms when applied beyond a primary development setting.

Sex Differences in Symptom Presentation in Acute Coronary Syndromes: A Systematic Review and Meta-analysis.

Background Timely recognition of patients with acute coronary syndromes (ACS) is important for successful treatment. Previous research has suggested that women with ACS present with different symptoms compared with men. This review assessed the extent of sex differences in symptom presentation in patients with confirmed ACS. Methods and Results A systematic literature search was conducted in PubMed, Embase, and Cochrane up to June 2019. Two reviewers independently screened title-abstracts and full-texts according to predefined inclusion and exclusion criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% CI of a symptom being present were calculated using aggregated and cumulative meta-analyses as well as sex-specific pooled prevalences for each symptom. Twenty-seven studies were included. Compared with men, women with ACS had higher odds of presenting with pain between the shoulder blades (OR 2.15; 95% CI, 1.95-2.37), nausea or vomiting (OR 1.64; 95% CI, 1.48-1.82) and shortness of breath (OR 1.34; 95% CI, 1.21-1.48). Women had lower odds of presenting with chest pain (OR 0.70; 95% CI, 0.63-0.78) and diaphoresis (OR 0.84; 95% CI, 0.76-0.94). Both sexes presented most often with chest pain (pooled prevalences, men 79%; 95% CI, 72-85, pooled prevalences, women 74%; 95% CI, 72-85). Other symptoms also showed substantial overlap in prevalence. The presence of sex differences has been established since the early 2000s. Newer studies did not materially change cumulative findings. Conclusions Women with ACS do have different symptoms at presentation than men with ACS, but there is also considerable overlap. Since these differences have been shown for years, symptoms should no longer be labeled as "atypical" or "typical."