Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events.

AIMS: Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2. METHODS AND RESULTS: Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. The SCORE2 was calculated in 4588 non-diabetic participants aged 46-68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). The SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed vs. 5.89% predicted, P < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed vs. 8.12% predicted, P = 0.043). CONCLUSION: Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk. LAY SUMMARIES: Subclinical carotid atherosclerosis is an important consideration in cardiovascular risk estimation by Systematic Coronary Risk Assessment 2 (SCORE2). Carotid ultrasound adds predictive performance to SCORE2 for assessment of cardiovascular risk. SCORE2 over-predicted the 10-year cardiovascular risk in those without carotid plaque while under-predicted the risk in those with carotid plaque.

The cost-effectiveness of a uniform versus age-based threshold for one-off screening for prevention of cardiovascular disease.

The objective of this article was to assess the cost-effectiveness of screening strategies for cardiovascular diseases (CVD). A decision analytic model was constructed to estimate the costs and benefits of one-off screening strategies differentiated by screening age, sex and the threshold for initiating statin therapy ("uniform" or "age-adjusted") from the Spanish NHS perspective. The age-adjusted thresholds were configured so that the same number of people at high risk would be treated as under the uniform threshold. Health benefit was measured in quality-adjusted life years (QALY). Transition rates were estimated from the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD), a large multicentre nested case-cohort study with 12 years of follow-up. Unit costs of primary care, hospitalizations and CVD care were taken from the Spanish health system. Univariate and probabilistic sensitivity analyses were employed. The comparator was no systematic screening program. The base case model showed that the most efficient one-off strategy is to screen both men and women at 40 years old using a uniform risk threshold for initiating statin treatment (Incremental Cost-Effectiveness Ratio of €3,274/QALY and €6,085/QALY for men and women, respectively). Re-allocating statin treatment towards younger individuals at high risk for their age and sex would not offset the benefit obtained using those same resources to treat older individuals. Results are sensitive to assumptions about CVD incidence rates. To conclude, one-off screening for CVD using a uniform risk threshold appears cost-effective compared with no systematic screening. These results should be evaluated in clinical studies.

Airspace Dimension Assessment with Nanoparticles (AiDA) in Comparison to Established Pulmonary Function Tests.

Background: Airspace Dimensions Assessment with nanoparticles (AiDA) is a new method for non-invasive measurement of pulmonary distal airspaces. The aim of this study was to compare AiDA measurements with other pulmonary function variables to better understand the potential of AiDA in a clinical context. Methods: AiDA measurements and pulmonary function tests were performed in 695 subjects as part of the Swedish CArdioPulmonary bioImage Study. The measurement protocol included spirometry, measurement of diffusing capacity of carbon monoxide, oscillometry and pulmonary computed tomography. AiDA indices were compared to all other pulmonary examination measurements using multivariate statistical analysis. Results: Our results show that AiDA measurements were significantly correlated with other pulmonary function examination indices, although covariance was low. We found that AiDA variables explained variance in the data that other lung function variables only influenced to a minor extent. Conclusion: We conclude that the AiDA method provides information about the lung that is inaccessible with more conventional lung function techniques.

Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema.

Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 µm vs 291±36 µm); OR for emphysema per 10 µm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 µm vs 291 µm±26 µm); OR per 10 µm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Measures of low lung function and the prediction of incident COPD events and acute coronary events.

BACKGROUND: Although reduced lung function is associated with both COPD and coronary events (CE), the pattern of lung function impairment could be different for the two outcomes. We examined different measures of lung function in relation to incident COPD events and CE in a population-based cohort. METHODS: Baseline spirometry and lung clearance index (LCI) were assessed in 672 men aged 55 years. Outcomes included incident COPD events and CE (hospitalisation or mortality). Cox regression was used to obtain HRs per 1-standard deviation (SD) decrement in baseline lung function. The Lunn-McNeil competing risks approach was used to assess if differences in risks for incident COPD events and CE were significant. RESULTS: Over 44 years follow-up there were 85 incident COPD events and 266 incident CE. Low FEV1 and FEV1/VC and high LCI showed significantly stronger relationships with COPD events than CE (adjusted HRs per 1SD decrement and p-value for equal associations: FEV1; HRCOPD: 2.11 (1.66-2.68), HRCE: 1.30 (1.13-1.49) p < 0.001, FEV1/VC; HRCOPD 1.95 (1.60-2.36), HRCE 1.11 (0.98-1.26) p < 0.0001, LCI; HRCOPD: 1.58 (1.26-1.98), HRCE: 1.14 (1.00-1.31) p = 0.015. Low VC was significantly associated with both COPD and CE, but HRs were not significantly different between the outcomes (p-value for equal associations = 0.706). CONCLUSIONS: Low FEV1 and FEV1/VC and high LCI at baseline show significantly stronger relationships with future COPD events than CE. Low VC at baseline is similarly associated with future COPD events and CE. This indicates differences but also an important similarity in the "lung function profile" for developing incident COPD events or incident CE later in life.

Anthropometric measures in relation to risk of heart failure hospitalization: a Swedish population-based cohort study.

BACKGROUND: It is unclear which anthropometric measure is most useful for assessment of the cardiovascular risk. We investigated the association between different anthropometric measures and risk of heart failure (HF) hospitalization. METHODS: BMI, waist-hip ratio (WHR), waist circumference (WC), body fat percentage (BF%), weight and height were measured among 26,653 subjects (aged 45-73 years) without history of myocardial infarction (MI), stroke or HF from the Malmö Diet and Cancer cohort at baseline in 1991-96. Incidence of HF hospitalizations was monitored during a mean follow-up of 15 years. RESULTS: Seven hundred and twenty-seven subjects were hospitalized with HF as primary diagnosis, of whom 157 had an MI before or concurrent with the HF. After adjustment for potential confounding factors, the hazard ratios of HF hospitalization (fourth vs. first sex-specific quartile) were 1.80 (95% CI: 1.45-2.24) for BMI, 1.87 (1.50-2.34) for WC, 1.77 (1.43-2.19) for WHR, 1.35 (1.09-1.68) for BF%, 1.93 (1.57-2.39) for weight and 1.18 (0.96-1.44) for height. Significant interactions between BMI and WC and WHR, respectively, were observed, and the joint exposure of high BMI and high WC or high WHR further increased the risk. The results were similar in secondary analyses, i.e., excluding incident HF with previous MI during the follow-up. CONCLUSION: Our results support the view that raised BMI, WC, WHR or BF% increases the risk of HF hospitalization. The joint exposure of high BMI and high WHR or high WC further increased the risk in an additive way.

A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene.

Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmö Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10,500 patients and 10,102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either.

Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation.

OBJECTIVES: the purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways. BACKGROUND: heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited. METHODS: in 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin. RESULTS: during a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c-statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification. CONCLUSIONS: conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.

Income and short-term case fatality after myocardial infarction in the whole middle-aged population of Malmö, Sweden.

BACKGROUND: There are no previous studies investigating when and where those who die pre-hospitally after an AMI paid their last visit to medical care. METHODS AND RESULTS: Incidence of AMI, pre-hospital and 28-day case fatality rates were monitored over 13 years of follow-up, in relation to sex-specific quartiles of annual income in all inhabitants aged 40-64 years in Malmö, Sweden. Both incidence and short-term case fatality were inversely related to income. In all, 60-70% of all deaths within 28 days after the AMI were pre-hospital deaths. As compared with the lowest income group, the highest income group had lower odds of pre-hospital death with an age- and time-to-event-adjusted odds ratio of 0.5 (95% CI 0.4-0.8) for men and 0.3 (95% CI 0.1-0.6) for women. On the other hand, while 72% of those in the lowest two income groups had paid a visit to the medical services during the three months before death, only 59% had done so in the two highest income groups (P < 0.05). CONCLUSIONS: Poor socioeconomic circumstances increase the risk of pre-hospital death after an AMI. Of the pre-hospital deaths, the proportion who had visited the medical services during the 3 months preceding their AMI was higher among those from lower income groups. However, many of those suffering a pre-hospital death had visited clinics that normally do not treat coronary symptoms. If more patients were identified at an earlier stage this might increase the number of patients reaching hospital alive.

Stroke incidence, recurrence, and case-fatality in relation to socioeconomic position: a population-based study of middle-aged Swedish men and women.

BACKGROUND AND PURPOSE: Low socioeconomic status is associated with increased incidence of stroke. This study investigated stroke incidence, recurrence, and case-fatality after stroke among middle-aged Swedish men and women and whether this association differs by gender or stroke subtype. METHODS: A total of 69 625 (49% men) citizens, aged 40 to 65 years, living in the city of Malmö in 1990 were studied in relation to total annual income and occupation class, ie, 2 indicators of socioeconomic status. Incidence of first-ever stroke, stroke recurrence, and case-fatality (death within 28 days or 1 year after stroke) were studied over 10 years of follow-up. RESULTS: During the follow-up, a total of 1648 subjects developed a first-ever stroke of whom 275 also experienced a recurrent stroke. By using Cox regression model with covariate adjustments, the incidence of stroke was significantly increased (relative risk: 1.75, 95% CI:1.36 to 2.25) in women who were in the lowest quartile of income compared with the women being in the highest quartile. Corresponding relative risk in men was 1.29 (1.06 to 1.58). Both in men and women, income was significantly associated with ischemic, but not hemorrhagic, subtypes of stroke. Similar relationships were observed between occupation level and incidence of stroke. In addition, low income was associated with higher 28-day and 1-year fatality rates in men (relative risk: 3.13, 1.35 to 7.24 and 2.17, 1.18 to 4.00, respectively), but not in women. In contrast, recurrence of stroke was inversely associated with income only in women. CONCLUSIONS: Incidence of stroke, stroke recurrence, and case-fatality increased with decreasing socioeconomic status; however, this relationship differed by gender and subtype of events.

C-reactive protein, established risk factors and social inequalities in cardiovascular disease - the significance of absolute versus relative measures of disease.

BACKGROUND: The widespread use of relative scales in socioepidemiological studies has recently been criticized. The criticism is based mainly on the fact that the importance of different risk factors in explaining social inequalities in cardiovascular disease (CVD) varies, depending on which scale is used to measure social inequalities. The present study examines the importance of established risk factors, as opposed to low-grade inflammation, in explaining socioeconomic differences in the incidence of CVD, using both relative and absolute scales. METHODS: We obtained information on socioeconomic position (SEP), established risk factors (smoking, hypertension, and hyperlipidemia), and low-grade inflammation as measured by high-sensitive (hs) C-reactive protein (CRP) levels, in 4,268 Swedish men and women who participated in the Malmö Diet and Cancer Study (MDCS). Data on first cardiovascular events, i.e., stroke or coronary event (CE), was collected from regional and national registers. Social inequalities were measured in relative terms, i.e., as ratios between incidence rates in groups with lower and higher SEP, and also in absolute terms, i.e., as the absolute difference in incidence rates in groups with lower and higher SEP. RESULTS: Those with low SEP had a higher risk of future CVD. Adjustment for risk factors resulted in a rather small reduction in the relative socioeconomic gradient, namely 8% for CRP (>/= 3 mg/L) and 21% for established risk factors taken together. However, there was a reduction of 18% in the absolute socioeconomic gradient when looking at subjects with CRP-levels < 3 mg/L, and of 69% when looking at a low-risk population with no smoking, hypertension, or hyperlipidemia. CONCLUSION: C-reactive protein and established risk factors all contribute to socioeconomic differences in CVD. However, conclusions on the importance of "modern" risk factors (here, CRP), as opposed to established risk factors, in the association between SEP and CVD depend on the scale on which social inequalities are measured. The one-sided use of the relative scale, without including a background of absolute levels of disease, and of what causes disease, can consequently prevent efforts to reduce established risk factors by giving priority to research and preventive programs looking in new directions.

Who are the "quitters"? a cross-sectional study of circumstances associated with women giving up smoking.

BACKGROUND: Smoking is an important preventable risk factor for cardiovascular disease, cancer, and many other diseases. Even though tobacco consumption is declining in Sweden, it is not declining in all groups. This study explored socioeconomic and psychosocial circumstances hindering or facilitating smoking cessation in three birth cohorts of women from the general population. METHODS: Between 1991 and 1996 a comprehensive questionnaire was administered to 17,319 women, 45-73 years old, from the Malmö Diet and Cancer cohort. Smoking habits were compared in relation to socioeconomic and psychosocial circumstances in three birth cohorts. RESULTS: Of these women, 44% were never smokers, 28% were ex-smokers, and 28% were smokers (regular or occasional). When compared with smokers, ex-smokers were more often married, had a higher socioeconomic position, a longer education, more smoke-free surroundings, better emotional support, higher BMI, and better self-perceived health. Ex-smokers reported less work-related stress and less shift work. A history of cardiovascular disease was not associated with smoking cessation. The socioeconomic differences between current and former smokers were higher for young women as compared with older birth cohorts. CONCLUSIONS: Continuing smokers and quitters differ with regard to socioeconomic and psychosocial circumstances and factors related to working life and environmental tobacco exposure. By determining who the quitters are through continued follow-up, useful insights can be gained to develop strategies to achieve successful cessation of smoking.

[Introduction of electronic monitoring increased interest for quality work. Nine-year-registration at Hjartcentrum indicates improved medical results]. / Elektronisk uppföljning okade intresset för kvalitetsarbete i Umeå. Nio ars registrering vid Hjärtcentrum visar att medicinska resultat förbättras.

Medical, administrative and economic data in a cardio-thoracic unit were followed for 9 years in an extensive monitoring system. Several changes in the practice could be observed. There was a general improvement in total quality factors seen as decreased complication rate especially in normal patients, a change in case mix towards older and more complicated patients and a decrease in the costs. The monitoring was a prerequisite for following, initiating and controlling changes. The article is published in English in Interactive Cardiovascular and Thoracic Surgery.