Association between the COVID-19 pandemic and mental health in very old people in Sweden.

BACKGROUND: During the COVID-19 pandemic, Sweden implemented social distancing measures to reduce infection rates. However, the recommendation meant to protect individuals particularly at risk may have had negative consequences. The aim of this study was to investigate the impact of the COVID-19 pandemic on very old Swedish peoples' mental health and factors associated with a decline in mental health. METHODS: We conducted a cross-sectional study among previous participants of the SilverMONICA (MONItoring of Trends and Determinants of CArdiovascular disease) study. Of 394 eligible participants, 257 (65.2%) agreed to participate. Of these, 250 individuals reported mental health impact from COVID-19. Structured telephone interviews were carried out during the spring of 2021. Data were analysed using the χ2 test, t-test, and binary logistic regression. RESULTS: Of 250 individuals (mean age: 85.5 ± 3.3 years, 54.0% women), 75 (30.0%) reported a negative impact on mental health, while 175 (70.0%) reported either a positive impact (n = 4) or no impact at all (n = 171). In the binary logistic regression model, factors associated with a decline in mental health included loneliness (odds ratio [95% confidence interval]) (3.87 [1.83-8.17]) and difficulty adhering to social distancing recommendations (5.10 [1.92-13.53]). High morale was associated with positive or no impact on mental health (0.37 [0.17-0.82]). CONCLUSIONS: A high percentage of very old people reported a negative impact on mental health from the COVID-19 pandemic, primarily from loneliness and difficulty adhering to social distancing measures, while high morale seemed to be a protective factor.

Self-rated health in old age, related factors and survival: A 20-Year longitudinal study within the Silver-MONICA cohort.

INTRODUCTION: Self-rated health (SRH) offers insights into the evolving health demographics of an ageing population. AIM: To assess change in SRH from old age to very old age and their associations with health and well-being factors, and to investigate the association between SRH and survival. METHODS: All participants in the MONICA 1999 re-examination born before 1940 (n = 1595) were included in the Silver-MONICA baseline cohort. The Silver-MONICA follow-up started in 2016 included participants in the Silver-MONICA baseline cohort aged 80 years or older. Data on SRH was available for 1561 participants at baseline with 446 of them also participating in the follow-up. The follow-up examination included a wide variety of measurements and tests. FINDINGS: Most participants rated their health as "Quite good" (54.5 %) at baseline. Over the study period, 42.6 % had stable SRH, 40.6 % had declined, and 16.8 % had improved. Changes in SRH were at follow-up significantly associated with age, pain, nutrition, cognition, walking aid use, self-paced gait speed, lower extremity strength, independence in activities of daily living, weekly physical exercise, outdoor activity, participation in organized activities, visiting others, morale, and depressive symptoms. SRH at baseline was significantly associated with survival (p < 0.05). CONCLUSION: This study demonstrates associations between changes in SRH and a multitude of health- and wellbeing-related factors, as well as a relation between survival and SRH, accentuating their relevance within the ageing population.

Increased carotid intima-media thickness in patients with radiographic axial spondyloarthritis compared to controls and associations with markers of inflammation.

OBJECTIVE: There is an increased risk for cardiovascular disease (CVD) in patients with radiographic axial spondyloarthritis (r-axSpA). In this cross-sectional study, we aimed to, overall and stratified by sex, (i) compare ultrasound derived carotid intima media thickness (cIMT), between patients and controls, and (ii) investigate associations between cIMT, clinical disease activity and inflammation-related laboratory markers in patients with r-axSpA. METHOD: In total, 155 patients diagnosed with r-axSpA using the modified New York criteria and 400 controls were included. Bilateral carotid ultrasound, laboratory testing, and questionaries were acquired. Disease-specific assessments were carried out for patients. Linear regression analysis was used to assess associations. RESULTS: Linear regression analyses showed that patients with r-axSpA had increased mean cIMT compared to controls (mean ± SD, 0.8 ± 0.1 mm vs 0.7± 0.1 mm, respectively, unstandardized ß (95% CI) -0.076 (-0.10, -0.052), P < 0.001) adjusted for smoking status and age. Linear regression analyses for patients with r-axSpA showed that only males presented significant associations between cIMT and inflammation-related laboratory markers, white blood cell (WBC) count (mean ± SD, 6.8 ± 1.6 109/L) and monocytes (0.6 ± 0.2 109/L); WBC count (unstandardized ß (95% CI) 0.019 (0.0065, 0.031), P = 0.003, R2 = 0.57) and monocytes (0.13 (0.0047, 0.26), P = 0.041, R2 = 0.55), adjusted for age, smoking status, body mass index, hypertension, dyslipidemia, diabetes mellitus, ASDAS-CRP, and treatment with DMARDs and glucocorticoids. No significant association was found between cIMT and clinical disease activity assessed by ASDAS-CRP. CONCLUSION: Patients with r-axSpA had significantly increased cIMT compared to controls. In male patients, higher WBC and monocyte count were associated with an increase in cIMT suggesting the role of inflammation in the development of atherosclerosis. Key Points •Carotid intima-media thickness was increased in patients with radiographic axial spondyloarthritis compared to controls. •White blood cell and monocyte counts were associated with carotid intima-media thickness in male patients with radiographic axial spondyloarthritis.

Preventive Interventions to Reduce the Burden of Rheumatic Heart Disease in Populations at Risk: A Systematic Review.

BACKGROUND: Rheumatic heart disease (RHD) is a devastating yet preventable condition that disproportionately affects low-middle-income countries and indigenous populations in some high-income countries. Various preventive interventions have been implemented across the globe, but evidence for the effectiveness of these measures in reducing the incidence or prevalence of acute rheumatic fever and RHD is scattered. This systematic review aims to assess the effectiveness of preventive interventions and identify the strategies used to reduce the burden of RHD. METHODS AND RESULTS: A comprehensive search was conducted to identify relevant studies on RHD prevention interventions including interventions for primordial, primary, and secondary prevention. Effectiveness measures for the interventions were gathered when available. The findings indicate that school-based primary prevention services targeting the early detection and treatment of Group A Streptococcus pharyngitis infection with penicillin have the potential to reduce the incidence of Group A Streptococcus pharyngitis and acute rheumatic fever. Community-based programs using various prevention strategies also reduced the burden of RHD. However, there is limited evidence from low-middle-income countries and a lack of rigorous evaluations reporting the true impact of the interventions. Narrative synthesis was performed, and the methodological quality appraisal was done using the Joanna Briggs Institute critical appraisal tools. CONCLUSIONS: This systematic review underscores the importance of various preventive interventions in reducing the incidence and burden of Group A Streptococcus pharyngitis, acute rheumatic fever, and RHD. Rigorous evaluations and comprehensive analyses of interventions are necessary for guiding effective strategies and informing public health policies to prevent and reduce the burden of these diseases in diverse populations. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020170503.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population. METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L). RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024). CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

Real-World Management of Patients with Pulmonary Arterial Hypertension: Insights from EXPOSURE.

INTRODUCTION: Further insights into real-world management and outcomes of patients with pulmonary arterial hypertension (PAH) are needed. This interim analysis of the ongoing, multicentre, prospective EXPOSURE (EUPAS19085) observational study describes characteristics, treatment patterns and outcomes of patients with PAH initiating a new PAH-specific therapy in Europe/Canada. METHODS AND RESULTS: All analyses were descriptive. In total, 1944 patients with follow-up information were included; the majority were female, with World Health Organization functional class II/III symptoms and with idiopathic PAH or connective tissue disease-associated PAH. Most incident patients (N = 1100; diagnosed for ≤ 6 months) initiated treatment as monotherapy (48%) or double therapy (43%). Of those initiating monotherapy, 38% (199/530) escalated to double therapy (median [Q1, Q3] time to escalation 3.4 [1.9, 6.6] months), and of those initiating double therapy, 17% (78/457) escalated to triple therapy (median [Q1, Q3] time to escalation 7.0 [3.4, 12.7] months) during the observation period (median [Q1, Q3]: 17.0 [7.5, 29.9] months). The majority of the 834 prevalent patients (diagnosed > 6 months) entered the study on initiation of combination therapy and most did not change treatment regimen during the observation period (median [Q1, Q3]: 19.6 [10.2, 32.2] months). One-year survival was 88% for incident patients and 90% for prevalent patients. CONCLUSIONS: Results from EXPOSURE suggest a shift towards combination therapy and the alignment of real-world treatment patterns with current guideline recommendations. While survival estimates are encouraging, the extent of monotherapy use at treatment initiation and follow-up highlight an opportunity for further improvements through optimisation of treatment strategies in line with current guidelines. A graphical abstract is also available with this article. TRIAL REGISTRATION NUMBER: EUPAS19085.

Pulmonary arterial hypertension (PAH) is a progressive disease. Clinical guidelines recommend that most patients start treatment with a combination of different PAH medications. While there is no cure for PAH, these medications help to control symptoms and slow disease worsening. To understand treatments currently used in clinical practice, we analysed data from EXPOSURE (EUPAS19085), an ongoing study collecting information from patients starting a new PAH medication in Europe and Canada. Most patients in the study were female, with World Health Organization functional class II/III symptoms, and idiopathic (unknown cause) PAH or PAH associated with connective tissue disorders. Among 1100 patients who were 'recently diagnosed' (diagnosed with PAH in the past 6 months), 88% were alive after 1 year. We found that 48% started treatment with one PAH medication, and 38% of those patients had a second medication prescribed within a median period of 3 months. Among the 457 'recently diagnosed' patients treated with two PAH medications when they entered the study, 17% had a third medication prescribed within a median period of 7 months. Among 834 patients with 'established PAH' (diagnosed more than 6 months ago), 90% were alive after 1 year. Most entered the study when they started a third medication and did not have further changes in treatment. Our findings show that patients with PAH are often treated with one medication in clinical practice as well as a combination of medications. While survival rates are encouraging, the extent to which one PAH medication is used suggests there is room for treatment improvement.

Long-term sequelae following acute pulmonary embolism: A nationwide follow-up study regarding the incidence of CTEPH, dyspnea, echocardiographic and V/Q scan abnormalities.

We aimed to follow a nationwide cohort of patients with pulmonary embolism (PE) without any exclusions to generate information regarding long-term symptoms, investigational findings and to determine the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that this approach would yield generalizable estimates of CTEPH prevalence and incidence. All individuals diagnosed with acute PE in Sweden in 2005 were identified using the National Patient Register. In 2007, survivors were asked to complete a questionnaire regarding current symptoms. Those with dyspnea were referred for further examinations with laboratory tests, electrocardiogram (ECG), and a ventilation/perfusion scan (V/Q scan). If CTEPH was suspected, a referral to the nearest pulmonary arterial hypertension-center was recommended. Of 5793 unique individuals with PE diagnosis in 2005, 3510 were alive at the beginning of 2007. Altogether 53% reported dyspnea at some degree whereof a large proportion had V/Q scans indicating mismatched defects. Further investigation revealed 6 cases of CTEPH and in parallel 18 cases were diagnosed outside this study. The overall prevalence of CTEPH was 0.4% (95% confidence interval [CI]: 0.2%-0.6%) and 0.7% (95% CI: 0.4%-1.0%) among the survivors. The cumulative incidence of CTEPH in the group of patients who underwent a V/Q scan was 1.1% (95% CI: 0.2%-2.0%). There was a high mortality following an acute PE, a high proportion of persistent dyspnea among survivors, whereof several had pathological findings on V/Q scans and echocardiography. Only a minority developed CTEPH, indicating that CTEPH is the tip of the iceberg of post-PE disturbances.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: An analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS: The study sample comprised 553818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors (sex, smoking, diabetes, non-HDL [high-density lipoprotein] cholesterol, systolic blood pressure [BP], and body mass index [BMI]) and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. RESULTS: The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the United Kingdom were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (p = 0.043 for overall difference) and those with diabetes had a slightly lower HR in central Europe (p = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol (7% per mmol/L; 95% confidence interval [CI], 3-10%) and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic CVD risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

Left ventricular hypertrophy: an ECG-based study of prevalence and risk factors in a multiethnic population.

BACKGROUND: Left ventricular hypertrophy (LVH) is frequently seen in association with arterial hypertension and indicates poor prognosis. This study aimed to determine the prevalence of LVH and associated factors in a multiethnic population from Mauritius. METHODS: Population-based health surveys were performed in 2009 and 2015 and included in total 8961 individuals aged 35-75 years with recorded 12-lead ECG. LVH was defined according to three criteria: Sokolow-Lyon, Cornell voltage and Cornell product. Data were collected about health and lifestyle behaviour. Anthropometry and blood pressure were measured. Fasting levels of blood lipids and glucose were determined, oral glucose tolerance test was performed in people without glucose-lowering medications. RESULTS: The age-standardised prevalence of LVH was 9% (n=875) according to any of the three ECG criteria. Individuals with LVH were older, more likely to have hypertension, diabetes, known cardiovascular disease (CVD) and elevated levels of cholesterol and creatinine. Further, they were more likely to be of African descent (Creole) and have lower educational level. In a multivariable model, Creole (OR (95% CI)) (1.56 (1.33 to 1.83)), low educational level (1.49 (1.28 to 1.75)), hypertension (3.01 (2.55 to 3.56)), known CVD (1.42 (1.11 to 1.83)) and elevated creatinine (1.08 (1.03 to 1.14)) remained associated with LVH. Individuals with non-treated or uncontrolled hypertension had a higher risk for LVH (3.09 (95% CI 2.57 to 3.71) and 4.07 (95% CI 3.29 to 5.05), respectively), than individuals with well controlled hypertension or normotension. CONCLUSION: LVH occurs more frequently in individuals with hypertension, as well as in individuals with African ancestry and/or low education level.

Soluble LDL-receptor is induced by TNF-α and inhibits hepatocytic clearance of LDL-cholesterol.

Defective LDL-C clearance and hence its elevation in the circulation is an established risk factor for cardiovascular diseases (CVDs) such as myocardial infarction (MI). A soluble LDL-receptor (sLDL-R) has been detected in human plasma which correlates strongly with circulating LDL-C and classical conditions that promote chronic inflammation. However, the mechanistic interplay between sLDL-R, inflammation, and CVDs remains to be investigated. Here, we report that stimulation of HepG2 cells with TNF-α induces the release of sLDL-R into culture supernatants. In addition, TNF-α induces gene expression of peptidases ADAM-17 and MMP-14 in HepG2 cells, and inhibiting these peptidases using TMI 1 significantly reduces the TNF-α induced sLDL-R release. We found that a soluble form of recombinant LDL-R (100 nM) can strongly bind to LDL-C and form a stable complex (KD = E-12). Moreover, incubation of HepG2 cells with this recombinant LDL-R resulted in reduced LDL-C uptake in a dose-dependent manner. In a nested case-control study, we found that baseline sLDL-R in plasma is positively correlated with plasma total cholesterol level. Furthermore, a twofold increase in plasma sLDL-R was associated with a 55% increase in the risk of future MI [AOR = 1.55 (95% CI = 1.10-2.18)]. Nevertheless, mediation analyses revealed that a significant proportion of the association is mediated by elevation in plasma cholesterol level (indirect effect ß = 0.21 (95% CI = 0.07-0.38). Collectively, our study shows that sLDL-R is induced by a pro-inflammatory cytokine TNF-α via membrane shedding. Furthermore, an increase in sLDL-R could inhibit hepatic clearance of LDL-C increasing its half-life in the circulation and contributing to the pathogenesis of MI. KEY MESSAGES: TNF-α causes shedding of hepatocytic LDL-R through induction of ADAM-17 and MMP-14. sLDL-R binds strongly to LDL-C and inhibits its uptake by hepatocytic cells. Plasma sLDL-R is positively correlated with TNF-α and cholesterol. Plasma sLDL-R is an independent predictor of myocardial infarction (MI). Plasma cholesterol mediates the association between sLDL-R and MI.

Health-related quality of life and healthcare consultations among adult patients before and after diagnosis with rheumatic heart disease in Namibia.

BACKGROUND: Rheumatic Heart Disease (RHD) causes high morbidity and mortality rates among children and young adults, impacting negatively on their health-related quality of life (HRQoL). This study aimed to evaluate the HRQoL and healthcare consultations of adult patients with RHD in Namibia. METHODS: From June 2019 to March 2020, a questionnaire was administered to 83 RHD patients during routine follow-ups. The EQ-5D-5L instrument was used to assess the health-related quality of life before diagnosis and at the time of the survey. The Ethiopian value set for EQ-5D-5L was used to calculate Quality-Adjusted Life Years (QALY). RESULTS: Most respondents were women (77%), young adults below the age of 30 years (42%), and individuals who grew up in rural areas (87%). The mean QALY statistically significantly improved from 0.773 pre-diagnosis to 0.942 in the last 12 months (p < 0.001). Sixty-six patients who had surgery reported a better QALY. Healthcare visits statistically significantly increased from on average 1.6 pre-diagnosis to 2.7 days in the last 12 months (p < 0.001). The mean distance to the nearest facility was 55 km, mean cost of transport was N$65, and mean time spent at the clinic was 3.6 h. The median time from diagnosis to the survey was 7 years (quartiles 4 and 14 years). CONCLUSION: Treatment and surgery can improve HRQoL substantially among RHD patients. Being diagnosed with RHD affects patients living in socioeconomically disadvantaged rural areas through cost and time for healthcare visits. It would be valuable with further research to understand differences between disease severities.

Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.

BACKGROUND: Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort. METHODS: The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination. RESULTS: Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants. CONCLUSIONS: In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.

Trends in renal function in Northern Sweden 1986-2014: data from the seven cross-sectional surveys within the Northern Sweden MONICA study.

OBJECTIVE: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time. DESIGN: Repeated cross-sectional population-based studies. SETTING: The two Northern counties (Norr- and Västerbotten) in Sweden. PARTICIPANTS: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185). INTERVENTIONS: None. MEASURES: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmö revised and Chronic Kidney Disease Epidemiology Collaboration (eGFRcrea) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFRcysC). Renal function over time was analysed using univariable and multivariable linear regression models. RESULTS: Renal function, both eGFRcrea and eGFRcysC, decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFRcrea and eGFRcysC (both p<0.001) after adjustment for classical cardiovascular RF. CONCLUSION: Renal function has deteriorated in Northern Sweden between 1986 and 2014.

Adipokines are possible risk markers for aortic stenosis requiring surgery.

OBJECTIVES: Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR). DESIGN: In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents. RESULTS: Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92-1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08-1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82-1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64-0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI). CONCLUSIONS: The adipokine leptin may promote the development of AS.

Patients with radiographic axial spondylarthritis have an impaired dietary intake-a cross-sectional study with matched controls from northern Sweden.

BACKGROUND: Radiographic axial spondyloarthritis (r-axSpA) is one of the most common chronic inflammatory rheumatic diseases, affecting about 0.2% of the Swedish population. Adequate nutritional intake is essential for maintaining physiological functions. A poor diet increases the risk of developing conditions such as obesity, osteoporosis, and/or atherosclerosis. Diet quality is also theorized to affect systemic inflammation. Dietary habits in patients with r-axSpA are largely unknown. The aims of this study were to assess dietary nutrient intake in r-axSpA patients and examine whether it differs compared to persons without r-axSpA. METHODS: r-axSpA patients (modified NY criteria) at the rheumatology clinic in Region Västerbotten, northern Sweden, were invited to take part in the Backbone study which investigates disease severity and comorbidities. In total, 155 patients were included. Nutritional intake was assessed by the semi-quantitative food frequency questionnaire MiniMeal-Q. Controls were collected from the Swedish CArdioPulmonary bioImage Study (n = 30,154), a study that invited participants 50-64 years of age by random selection from the Swedish population register. Out of the 155 r-axSpA patients, 81 were in the same age span. Four controls were identified for each patient, matched on age (± 1 year), sex, and geographic location. Data on dietary intake was available for 319 controls. Statistical comparisons of dietary intake between patients with r-axSpA and controls were done by exact conditional logistic regression analysis, adjusted for country of birth, educational level, single household, weight, smoking status, and energy intake. RESULTS: Patients had a comparatively significantly higher energy intake from carbohydrates, a lower fiber density, and a lower intake of marine omega-3 fatty acids. Furthermore, intake of vitamins D, E, and K as well as selenium, folate, calcium, magnesium, phosphorus, potassium, vitamin A, and ß-carotene (a precursor of vitamin A and marker of vegetable and fruit intake) was significantly lower among patients compared to controls. CONCLUSIONS: Our results suggest that r-axSpA patients have an impaired dietary intake. Notably, intake was lower in several nutrients theorized to have anti-inflammatory properties (fiber density, marine-omega-3 fatty acids, vitamin D, and selenium). We further propose that nutrition screening might be incorporated into the management of r-axSpA patients.

Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population.

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥ 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis ≥ 50% (OR 1.27, 95% CI 1.09-1.47), ≥ 4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Association between snus use and lipid status in Swedish men.

Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.

Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.

Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe. Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome. Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80). Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.