Significance of serological atrophic gastritis on proton pump inhibitor prescriptions and referrals to gastroscopy in the general population.

Background and Aim: We aimed to investigate whether individuals with low pepsinogen I levels differed from those with normal pepsinogen I levels in terms of proton pump inhibitors (PPIs) use, referral to gastroscopy, and findings on gastroscopy. Methods: Serum pepsinogen I was measured in 518 persons (mean age 51.6, SD 8.8; 49% women). A medical chart review focused on PPI prescriptions and gastroscopic findings in the follow-up period. Results: Patients with serological atrophic gastritis (pepsinogen I < 28 µg/L) had higher body mass index (27.5 vs 26.2 kg/m2; P = 0.007), were less likely to be current smokers (8% vs 17%; P = 0.025), and had higher prevalence of Helicobacter pylori seropositivity (57% vs 36%; P < 0.001) compared with those without. During follow-up (mean 21.4 years, SD 6.5 years), the patients with serological atrophic gastritis had more often findings of atrophic gastritis or gastric polyps on gastroscopy (20% vs 8%; P < 0.001), despite no differences in the mean number of gastroscopies per 1000 person-years (33 vs 23; P = 0.19) and the mean prescribed PPI dose (omeprazole equivalents) per year (1064 mg vs 1046 mg; P = 0.95). Persons with serological atrophic gastritis had lower odds of being prescribed PPIs at least once (odds ratio [95% confidence interval]: 0.58 [0.35-0.96]), but there was no significant difference in the chance of being referred to gastroscopy at least once (1.15 [0.70-1.96]). Conclusion: Persons with serological atrophic gastritis were less likely to be prescribed PPIs. Persons with serological atrophic gastritis had more often gastric polyps and atrophic gastritis when referred to gastroscopy.

Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.

RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure. OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population. METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7. RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

INTRODUCTION: Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. METHODS: Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. RESULTS: As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60 years and prevalent (2 years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68 years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. CONCLUSIONS: In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Pulmonary arterial hypertension (PAH) is a disease that gets worse over time. To make decisions about treatment, we need to know the stage of the disease. We can do this by measuring the patient's risk of death during the next few years. Selexipag is a medication for PAH. This analysis included patients living in Europe and Canada who started treatment with selexipag for their PAH disease. Our findings suggest that the monitoring of patients' health and the timing of starting selexipag can be improved. This analysis includes 698 patients taking part in the EXPOSURE study (EUPAS19085), which looks at the real-life treatment of patients with PAH. Overall, 71% of patients were female, the median age was 60 years, most had been diagnosed with PAH for around 2 years and were already taking two other medications for their PAH disease. At the beginning of selexipag treatment, 14% of patients were classified as low risk, 31% as intermediate-low risk, 34% as intermediate-high risk and 20% as high risk of mortality within the next year. More high-risk patients were hospitalised compared with the lower risk groups. After 1 year of treatment, more patients in the low (98%) and intermediate-low groups (98%) were alive than those in the intermediate-high (93%) and high risk groups (80%). The same was true after 2 years of treatment with selexipag (98%, 92%, 81% and 67%, respectively). This study confirms that assessing patients' risk levels can indicate how well they will do over time and shows that earlier treatment with selexipag should be considered to potentially prevent worsening of the disease.

Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults.

PURPOSE: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths. METHODS: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17-39 years at baseline in 1963-2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975-1985, ≥1985 and women: <1985, 1985-1994, ≥1995). RESULTS: Comparing men with obesity vs. normal weight, all-cause and "other-cause" mortality associations decreased over periods; HR (95% CI) 1.92 (1.83-2.01) and 1.70 (1.58-1.82) for all-cause and 1.72 (1.58-1.87) and 1.40 (1.28-1.53) for "other-cause" mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51-2.94) and 3.91 (3.37-4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women. CONCLUSIONS: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

BACKGROUND: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. OBJECTIVES: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. METHODS: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). RESULTS: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). CONCLUSIONS: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Cost-effectiveness of applying high-sensitivity troponin I to a score for cardiovascular risk prediction in asymptomatic population.

INTRODUCTION: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. METHODS: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. RESULTS: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20-26) additional event-free years and 7 (95%CI: 5-9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3-13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. CONCLUSION: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Coronary Plaque in People With HIV vs Non-HIV Asymptomatic Community and Symptomatic Higher-Risk Populations.

Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification. Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH. Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence. Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001). Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.

Prevalence and social determinants of smoking among men in Mauritius: a cross-sectional study.

BACKGROUND: Mauritius has implemented a range of stringent policies to control smoking and promote public health. Regular monitoring focuses on the prevalence of tobacco use, yet there is a gap in understanding its socio-economic patterns. OBJECTIVE: The aim of this study was to estimate the prevalence of tobacco smoking and to identify the social determinants associated with smoking among men in Mauritius in 2021. METHODS: This is a cross-sectional population-based study conducted by the Ministry of Health and Wellness during 2021. In total, 3622 individuals participated (response rate of 84.1%), of which 1663 were men (45.9%). The study mainly focused on men given the low prevalence of smoking among women. Daily smoking was the outcome and a series of sociodemographic and socioeconomic factors were included as independent variables. Prevalence ratios (PR) and their 95% confidence intervals (95% CI) were estimated to fulfill the study objective. RESULTS: The prevalence of smoking among men was 30.4%. People in the 25-34 age group (PR = 1.65; 95% CI: 1.12-2.41), those separated, divorced or widowed (PR = 1.57; 95% CI: 1.16-2.11), the ethnic groups Muslim-Mauritians (PR = 1.70; 95% CI: 1.00-2.89) and Creoles (PR = 1.97; 95% CI: 1.16-3.35), and those with secondary (PR = 1.29; 95% CI: 1.00-1.67) and primary education (PR = 1.47; 95% CI: 1.10-1.98) were statistically significantly associated with daily smoking. CONCLUSIONS: Although a gradual decline in smoking prevalence was observed compared with the previous 2015 survey, the Ministry of Health and Wellness should persist in fortifying its anti-smoking measures and concentrate on crafting tailored interventions aimed at the vulnerable groups identified in this study.

Main findings: This study found a prevalence of smoking of 30.4% among men in Mauritius, identifying the young population, those not married, the Muslim-Mauritians and Creole ethnic groups and those with secondary and primary education as at-risk groups for smoking.Added knowledge: The study provides updated information on the prevalence of smoking and its distribution among different socioeconomic groups in Mauritius.Global health impact for policy and action: The anti-smoking policies implemented by the Ministry of Health and Wellness should continue to be strengthened, and specific interventions for the identified at-risk groups be developed. This can serve as a model for other countries with similar socio-economic profiles, aiming to reduce smoking consumption.

Eligibility for lipid-lowering therapy when applying systemic coronary risk estimation 2 (SCORE2) according to guidelines on apparently healthy middle-aged individuals.

AIMS: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. METHODS: Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). RESULTS: Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. CONCLUSIONS: Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

KEY QUESTIONS: What proportion of an apparently healthy middle-aged population would be eligible for lipid-lowering therapy (LLT) according to the 2021 ESC guidelines when using SCORE2? What proportion of those eligible for LLT have atherosclerosis according to coronary imaging? KEY FINDING: According to the guidelines, nearly all individuals categorized as high and very-high risk according to the SCORE2 equation, or 35% of the total population, were eligible for LLT, of which 38% had no signs of coronary atherosclerosis. These proportions increased when the SCORE2 multicell chart was used. TAKE-HOME MESSAGE: Implementing SCORE2 and the ESC guidelines would result in more than one in three apparently healthy middle-aged individuals being eligible for LLT. A significant proportion would have no signs of coronary atherosclerosis.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

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.

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.

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.

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.

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.

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.