Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease ...progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
Aims
Heart failure (HF) quality registries report quality of care but it is unknown whether they improve outcomes. The aims were to assess predictors of enrolment in a HF registry, test the ...hypothesis that enrolment in a HF registry is associated with reduced mortality, and assess potential explanatory factors for this reduction in mortality, if present.
Methods and results
We conducted a nationwide prospective cohort study of patients with new‐onset HF registered in the Swedish National Patient Registry (NPR, a mandatory registry of ICD‐code diagnoses) with or without concurrent registration in the Swedish Heart Failure Registry (SwedeHF, a voluntary quality reporting registry) 2006–2013. The association between demographics, co‐morbidities and medications, and enrolment in the SwedeHF, was assessed using multivariable logistic regression. The association between enrolment in the SwedeHF and all‐cause mortality was assessed using multivariable Cox regression, with adjustment for demographics, co‐morbidities and medications. A total of 231 437 patients were included, of which 21 888 (9.5%) were in the SwedeHF age (mean ± standard deviation) 74 ± 13 years; 41% women; 68% inpatients and 209 549 (90.5%) were not (age 78 ± 12 years, 50% women; 79% inpatients). Selected variables independently associated with enrolment in the SwedeHF were male sex, younger age, higher education, absent co‐morbidities and co‐morbidity‐related medications, and use of HF and cardiovascular medications. Over a median (interquartile range) follow‐up of 874 (247–1667) days, there were 13.0 vs. 20.8 deaths per 100 patient‐years (P < 0.001). The hazard ratio (95% confidence interval) for death for the SwedeHF yes vs. no was 0.65 (0.63–0.66) crude, and increased to 0.80 (0.78–0.81) after adding demographics, to 0.82 (0.80–0.84) after adding co‐morbidities and co‐morbidity‐related medications, to 0.95 (0.93–0.97) after adding cardiovascular medications, and to 1.04 (1.02–1.07) after adding HF‐specific medications.
Conclusion
Heart failure patients of male sex, younger age, and higher education were more likely to be enrolled in a HF quality registry. Enrolment was associated with reduced all‐cause mortality that was explained by demographic differences and better utilization of cardiovascular and HF medications.
Aim
Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF), but are underutilized. Hyperkalaemia may be one reason, but the underlying ...reasons for underuse are unknown. The aim of this study was to investigate the independent predictors of MRA underuse in a large and unselected HFrEF cohort.
Methods and results
We included patients with HFrEF (ejection fraction <40%), New York Heart Association (NYHA) class II–IV and heart failure (HF) duration ≥6 months from the Swedish HF Registry. Logistic regression analysis identified independent associations between 39 demographic, clinical, co‐treatment, and socioeconomic predictors and MRA non‐use. Of 11 215 patients, 27% were women; mean age was 75 ± 11 years; only 4443 (40%) patients received MRA. Selected characteristics independently associated with MRA non‐use were in descending order of magnitude: lower creatinine clearance (<60 mL/min), no need for diuretics, no cardiac resynchronization therapy/implantable cardioverter‐defibrillator, higher blood pressure, no digoxin use, higher ejection fraction, outpatient setting, older age, lower income, ischaemic heart disease, male sex, follow‐up in primary vs. specialty care, lower NYHA class, and absence of hypertension diagnosis. Plasma potassium and N‐terminal pro B‐type natriuretic peptide levels were not associated with MRA non‐use.
Conclusion
Mineralocorticoid receptor antagonists remain underused in HFrEF. Their use does not decrease with elevated potassium but does with impaired renal function, even in the creatinine clearance 30–59.9 mL/min range where MRAs are not contraindicated. MRA underuse may be further related to non‐specialist care, milder HF and no use of other HF therapy.
Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist.
To evaluate the consistency of evidence associating modifiable lifestyle ...factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m
). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria).
We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio OR, 0.78; 95% confidence interval 95% CI, 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding.
These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.
SCREAM (Stockholm CREAtinine Measurements project) was initiated in 2010 in collaboration with the healthcare provider of Stockholm County healthcare to quantify potential medication errors, estimate ...the burden of chronic kidney disease (CKD) and to illustrate the value of incorporating measures of kidney function into the medical decision process. Because most patients are unaware of their CKD and diagnoses are seldom issued, SCREAM took advantage of the commonness of serum/plasma creatinine testing, which can be used to estimate the glomerular filtration rate (eGFR) and classify the stage of CKD severity. SCREAM is periodically updated, and at present contains healthcare information of all residents in Stockholm region during 2006–2019 (about 3 million people), enriched with a broad range of laboratory measurements for those in whom creatinine or albuminuria has been measured (about 1.8 million people). This health information was linked with national administrative and quality registries via the unique personal identification number of each Swedish citizen, conforming the richest characterization in Sweden of the population's journey through health and disease. This review discusses the context of its creation, strengths and weakness, key findings and plans for the future. We summarize our findings related to the burden of CKD in Sweden, its adverse health risks (such as risk of infections, cancer or dementia) and how underlying kidney function alters the risk–benefit ratio of common medications. Results have had clinical impact and demonstrate the importance of population‐based research in the spectrum of clinical research to improve health.
Patients with CKD are advised to follow dietary recommendations that restrict individual nutrients. Emerging evidence indicates overall eating patterns may better predict clinical outcomes, however, ...current data on dietary patterns in kidney disease are limited.
This systematic review aimed to evaluate the association between dietary patterns and mortality or ESRD among adults with CKD. Medline, Embase, and reference lists were systematically searched up to November 24, 2015 by two independent review authors. Eligible studies were longitudinal cohort studies reporting the association of dietary patterns with mortality, cardiovascular events, or ESRD.
A total of seven studies involving 15,285 participants were included. Healthy dietary patterns were generally higher in fruit and vegetables, fish, legumes, cereals, whole grains, and fiber, and lower in red meat, salt, and refined sugars. In six studies, healthy dietary patterns were consistently associated with lower mortality (3983 events; adjusted relative risk, 0.73; 95% confidence interval, 0.63 to 0.83; risk difference of 46 fewer (29-63 fewer) events per 1000 people over 5 years). There was no statistically significant association between healthy dietary patterns and risk of ESRD (1027 events; adjusted relative risk, 1.04; 95% confidence interval, 0.68 to 1.40).
Healthy dietary patterns are associated with lower mortality in people with kidney disease. Interventions to support adherence to increased fruit and vegetable, fish, legume, whole grain, and fiber intake, and reduced red meat, sodium, and refined sugar intake could be effective tools to lower mortality in people with kidney disease.
Anemia is a common complication of chronic kidney disease (CKD), but limited awareness and treatment options may hinder its management among CKD patients followed in primary care.
We evaluated adults ...with CKD stages 3-5 attending primary care in Stockholm, Sweden, 2012-2018. We assessed the incidence of anemia, clinical reactions, and association with subsequent major adverse cardiovascular events (MACE) and death.
We identified 45,637 patients with CKD stages 3-5 free from anemia (mean age 78 years; 64% females; 79% CKD stage 3b). During a median follow-up of 2.4 years, 26% of patients developed anemia, and 10.4% developed severe anemia (hemoglobin <10 g/dL). Within 6 months from the anemia event, iron tests were infrequent; ferritin and transferrin saturation were tested in 27% and 11% of anemia cases, respectively, and 49% and 24% of severe anemia cases. Few patients were recognized with a clinical diagnosis (15% of anemia cases; 68% of severe anemias). Only 19% of patients with anemia received treatment, primarily iron (10%) and blood transfusions (7%); erythropoietin-stimulating agent use was anecdotal (∼1%). Treatment rates for severe anemia were higher, but 43% of patients still failed to receive treatment. Developing anemia was associated with a higher risk of MACE and death.
Anemia was common and associated with adverse outcomes among patients with CKD stages 3-5 managed in primary care. Iron stores were infrequently tested, and a large proportion of patients with anemia remained untreated/under-recognized.
Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.
Four versions of the CCI were ...compared and evaluated by disease-specific experts.
We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.
This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
Background
Concerns about hyperkalemia limit the use of angiotensin‐converting enzyme inhibitors (ACE‐I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding ...potassium‐monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE‐I/ARB initiation and developed and validated a hyperkalemia susceptibility score.
Methods and Results
We evaluated 69 426 new users of ACE‐I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow‐up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity‐matched new ACE‐I/ARB users to 20 186 new β‐blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β‐blocker and ACE‐I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m2 were risks higher among ACE‐I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium‐sparing diuretics in new ACE‐I/ARB users; this score accurately predicted 1‐year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840–0.869) and in a validation cohort from the US‐based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794–0.841), with good calibration.
Conclusions
Hyperkalemia within the first year of ACE‐I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m2, but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.
There are no studies of long-term worsening renal function (WRF) in heart failure (HF) with different ejection fraction (EF) groups. The aim was to compare incidence of, associations with and ...prognostic impact of WRF in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced EF (HFrEF). The Swedish Heart Failure Registry (SwedeHF) was merged with the Stockholm Creatinine Measurement (SCREAM) registry 2006 to 2010. The associations between EF and WRF (≥25% decrease in eGFR) and the associations between WRF25-49% and WRF≥50% within year one and subsequent all-cause mortality were all assessed with multiadjusted Cox regression. Of 7,154 patients, 41.6% of HFpEF versus 34.5% and 35.4% of HFmrEF and HFrEF patients developed WRF≥25% during year one. The WRF risk was higher in HFpEF (reference) than in HFmrEF, hazard ratio (95% confidence interval) 0.890 (0.794 to 0.997) and HFrEF 0.870 (0.784 to 0.965). WRF within year one was strongly associated with subsequent long-term mortality in all EF groups, yielding adjusted HRs with WRF25-49% and WRF≥50%: HFpEF, 1.101 (0.913 to 1.328) and 2.096 (1.652 to 2.659), in HFmrEF 1.654 (1.353 to 2.022) and 2.375 (1.807 to 3.122) and in HFrEF 1.212 (1.060 to 1.386) and 1.694 (1.412 to 2.033). In conclusion, the long-term WRF risk was high in HF and highest in HFpEF. WRF was strongly associated with mortality in all EF groups, although in HFpEF only with the most severe WRF.
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