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.

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.

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

BACKGROUND: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. METHODS: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. RESULTS: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. CONCLUSIONS: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

The inverse association between a fish consumption biomarker and gingival inflammation and periodontitis: A population-based study.

AIM: The metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish-intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as the extent and severity variables. MATERIALS AND METHODS: The Malmö Offspring Study is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography-mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, body mass index, fasting glucose, and smoking. RESULTS: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (ß = -2.12, p = .002) and lower odds of severe periodontitis (odds ratio [OR] = 0.74, 95% confidence interval [CI]: 0.56 to 0.98). Higher CMPF levels were also associated with more teeth (ß = 0.19, p = .001), lower number of periodontal pockets (≥4 mm) (ß = -1.07, p = .007), and lower odds of having two or more periodontal pockets of ≥6 mm (OR = 0.80, 95% CI: 0.65 to 0.98) in fully adjusted models. CONCLUSIONS: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out, and future studies are warranted.

Accelerometer derived physical activity patterns in 27.890 middle-aged adults: The SCAPIS cohort study.

The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50-64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an "at-risk" behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.

The Malmö Offspring Study (MOS): design, methods and first results.

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

Comparison of risk factors for ischemic stroke and coronary events in a population-based cohort.

BACKGROUND: Although coronary events (CE) and ischemic stroke share many risk factors, there are also some important differences. The aim of this paper was to assess the association of risk factors in relation to incident CE and ischemic stroke and to evaluate the heterogeneity in patterns of risk factors between the two outcomes. METHOD: Traditional risk factors and inflammatory markers associated with coronary events and ischemic stroke were measured in the Malmö Diet and Cancer Cohort (MDCS, n = 26 519), where a total of 2270 incident ischemic stroke and 3087 incident CE occurred during a mean follow up time 19 ± 6 years, and in relation to inflammatory markers in the cardiovascular sub-cohort (MDC-CV, n = 4795). Cox regression analysis was used to obtain hazard ratios. A modified Lunn-McNeil competing risk analysis was conducted to assess the significance of any differences in risk profiles of these outcomes. RESULTS: Most cardiovascular risk factors were associated both with incident CE and ischemic stroke. However, current smoking, ApoB, low ApoA1, male sex and education level of ≤ 9 years of schooling were preferentially associated with CE compared to ischemic stroke. Conversely, age showed a stronger association with ischemic stroke than with CE. CONCLUSION: CE and ischemic stroke have broadly similar risk factors profiles. However, there are some important differential associations, as well as substantial differences in the magnitude of the association. These could reflect the distinct biology of atherogenesis in different vascular beds. The difference in the determinants highlights the importance of looking at CE and ischemic stroke, two manifestations of cardiovascular disease, separately.

Glucose-dependent insulinotropic peptide and risk of cardiovascular events and mortality: a prospective study.

AIMS/HYPOTHESIS: Evidence that glucose-dependent insulinotropic peptide (GIP) and/or the GIP receptor (GIPR) are involved in cardiovascular biology is emerging. We hypothesised that GIP has untoward effects on cardiovascular biology, in contrast to glucagon-like peptide 1 (GLP-1), and therefore investigated the effects of GIP and GLP-1 concentrations on cardiovascular disease (CVD) and mortality risk. METHODS: GIP concentrations were successfully measured during OGTTs in two independent populations (Malmö Diet Cancer-Cardiovascular Cohort [MDC-CC] and Prevalence, Prediction and Prevention of Diabetes in Botnia [PPP-Botnia]) in a total of 8044 subjects. GLP-1 (n = 3625) was measured in MDC-CC. The incidence of CVD and mortality was assessed via national/regional registers or questionnaires. Further, a two-sample Mendelian randomisation (2SMR) analysis between the GIP pathway and outcomes (coronary artery disease [CAD] and myocardial infarction) was carried out using a GIP-associated genetic variant, rs1800437, as instrumental variable. An additional reverse 2SMR was performed with CAD as exposure variable and GIP as outcome variable, with the instrumental variables constructed from 114 known genetic risk variants for CAD. RESULTS: In meta-analyses, higher fasting levels of GIP were associated with risk of higher total mortality (HR[95% CI] = 1.22 [1.11, 1.35]; p = 4.5 × 10-5) and death from CVD (HR[95% CI] 1.30 [1.11, 1.52]; p = 0.001). In accordance, 2SMR analysis revealed that increasing GIP concentrations were associated with CAD and myocardial infarction, and an additional reverse 2SMR revealed no significant effect of CAD on GIP levels, thus confirming a possible effect solely of GIP on CAD. CONCLUSIONS/INTERPRETATION: In two prospective, community-based studies, elevated levels of GIP were associated with greater risk of all-cause and cardiovascular mortality within 5-9 years of follow-up, whereas GLP-1 levels were not associated with excess risk. Further studies are warranted to determine the cardiovascular effects of GIP per se.

Blood cadmium concentration and risk of subarachnoid haemorrhage.

BACKGROUND: Cadmium is a toxic metal and exposure is mainly from diet and tobacco smoke. Cadmium is accumulated in blood vessels and may reduce synthesis of procollagen and inhibit proliferation of vascular smooth muscle cells. High blood cadmium has been associated with increased risk of myocardial infarction, stroke and unruptured intracranial aneurysms. We examined whether blood cadmium increase the risk of subarachnoid haemorrhage (SAH). METHODS: The Malmö Diet and Cancer cohort (n = 28,449) was examined in 1991-1996 and blood samples were taken. Incidence of SAH was followed up to 2014. Cadmium was measured in stored blood samples from incident SAH cases and matched controls (n = 93 vs n = 276) and odds ratio (OR) for SAH was assessed in a nested case control design. RESULTS: Subjects with cadmium concentration in the highest quartile had increased risk of SAH compared to those in the first quartile (OR: 3.22, 95%CI: 1.67-6.22). However, after adjusting for smoking, results were weakened and non-significant (OR: 1.57, 95%CI: 0.51-4.80). CONCLUSIONS: Cadmium concentration was associated with increased risk of SAH but this association was largely explained by smoking. Whether cadmium in tobacco may contribute to the vascular pathology and increased risk of SAH in smokers should be further studied.

Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers: results from a population-based proteomics study.

BACKGROUND: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. METHODS: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant proteins were then studied in relation to incidence of CVD (i.e., coronary events or ischemic stroke) in never smokers. RESULTS: Fifteen proteins were associated with B-Cd in never smokers. Eight of them were replicated in long-term former smokers. Kidney injury molecule-1, fibroblast growth factor-23 (FGF23), tumor necrosis factor receptor-2, matrix metalloproteinase-12, cathepsin L1, urokinase plasminogen activator receptor, C-C motif chemokine-3 (CCL3), and chemokine (C-X3-C motif) ligand-1 were associated with B-Cd both in never smokers and long-term former smokers. Except for CCL3 and FGF23, these proteins were also significantly associated with incidence of CVD. CONCLUSIONS: B-Cd in non-smokers was associated with eight potential plasma biomarkers of CVD and kidney injury. The results suggest pathways for the associations between B-Cd and CVD and kidney injury.