Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease.Design Mendelian randomisation meta-analysis of ...individual participant data from 47 epidemiological studies in 15 countries.Participants 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors.Main outcome measures Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals.Results CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P<10−34) and were unrelated to other risk factors. Risk ratios for coronary heart disease per additional copy of an allele associated with raised C reactive protein were 0.93 (95% confidence interval 0.87 to 1.00) for rs3093077; 1.00 (0.98 to 1.02) for rs1205; 0.98 (0.96 to 1.00) for rs1130864; and 0.99 (0.94 to 1.03) for rs1800947. In a combined analysis, the risk ratio for coronary heart disease was 1.00 (0.90 to 1.13) per 1 SD higher genetically raised natural log (ln) concentration of C reactive protein. The genetic findings were discordant with the risk ratio observed for coronary heart disease of 1.33 (1.23 to 1.43) per 1 SD higher circulating ln concentration of C reactive protein in prospective studies (P=0.001 for difference).Conclusion Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.
Summary
Background
Despite numerous risk factors and serious consequences, little is known about metabolic dysfunction‐associated steatotic liver disease (MASLD) at population level in Africa.
Aim
...The aim of the study was to estimate the prevalence and risk factors of MASLD in people living with and without HIV in Uganda.
Methods
We collected data from 37 communities in South Central Uganda between May 2016 and May 2018. We estimated MASLD prevalence using the fatty liver index and advanced liver fibrosis using the dynamic aspartate‐to‐alanine aminotransferase ratio. We collected additional data on sociodemographics, HIV and cardiovascular disease (CVD) risk factors. We used multivariable logistic regression to determine the association between HIV, CVD risk factors and MASLD.
Results
We included 759 people with HIV and 704 HIV‐negative participants aged 35–49. MASLD prevalence was 14% in women and 8% in men; advanced liver fibrosis prevalence was estimated to be <1%. MASLD prevalence was more common in women (15% vs. 13%) and men (9% vs. 6%) with HIV. Being female (odds ratio OR = 2.1; 95% confidence interval CI = 1.4–3.3) was associated with a higher odds of MASLD after adjustment for confounders; HIV infection was borderline associated with MASLD (OR = 1.4; 95% CI: 1.0–2.0).
Conclusions
In a relatively young cohort in Uganda, 14% of women and 8% of men had MASLD. There was an indication of an association between HIV and MASLD in multivariable analysis. These data are the first to describe the population‐level burden of MASLD in sub‐Saharan Africa using data from a population‐based cohort.
Prevalence and risk factors of metabolic dysfunction‐associated steatotic liver disease in south Central Uganda: A cross‐sectional survey.
Graphical Abstract
Graphical Abstract
Pros and cons of a healthcare cost-driven strategy. Chest pain is among the most common diagnoses for admission to the emergency department (ED). The current ...strategy for assessment and management of patients with chest pain with suspected acute coronary syndrome (ACS) is to be referred to the ED regardless of the estimated cardiovascular risk. This in turn may result in overcrowding of the ED and increased costs for the healthcare system. The ARTICA trial proposes a healthcare cost-driven strategy and shows that ambulance triage of patients with chest pain can identify patients at low risk of ACS that can be referred to the general practitioner. From a healthcare cost perspective, pre-hospital assessment of ACS risk can reduce the healthcare costs by reducing the number of ED referrals and promote an effective use of health resources. At present, several questions need to be addressed before pre-hospital triage can be implemented: safety and sustainability in different healthcare systems and validation of the troponin point of care measurements.
The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction ...beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmö Diet and Cancer study-cardiovascular cohort).
This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated.
All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n=5180), WHHR was the only measure that improved Cox regression models in men (P=0.01).
WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.
It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between ...biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.
After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 95% CI, 1.02-1.16;
=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.
A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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.
Abstract
Background
Pro-inflammatory interleukin 6 (IL6) trans-signalling is associated with an increased risk of future cardiovascular events (CVE). Diabetes mellitus is a well-known risk factor for ...CVE but its relation to IL6 trans-signalling is not investigated.
Purpose
We aimed at analysing if the CVE risk associated with IL6 trans-signalling differed between individuals with/without diabetes.
Method
In a prospective cohort of 60-year-old men and women from our city (n=4232), 629 CVE (myocardial infarction, hospitalised angina pectoris and ischemic stroke) occurred during a 20-year follow-up. The risk of CVE associated with IL6 trans-signalling was assessed using the binary/ternary complex ratio (B/T ratio), a novel marker of IL6 trans-signalling derived from the serum molar concentrations of IL6 and the soluble IL6 receptors (sIL6R; sgp130). As a B/T ratio > median, mirroring active IL6 trans-signalling with a relative excess of the active binary IL6 complex in relation to the inactive ternary complex, previously was demonstrated to be associated with an increased CVE risk in this cohort we chose the same cut-off. The CVE risk was assessed by Cox proportional hazards models and described as hazard ratios (HR) with 95% confidence intervals (CI) in individuals with/without diabetes mellitus type 1 or 2 (n=114) defined as either self-reported, or fasting glucose >7.0 mmol/L in the baseline blood test. In the adjusted model, risk estimates were adjusted for the common cardiovascular risk factors. The additive interaction between IL6 trans-signalling and diabetes on the CVE risk was analysed using Cox regression and presented as Synergy index (S) with 95% CI where S > or <1 indicate presence of an interaction.
Result
There was a higher CVE risk associated with IL6 trans-signalling assessed by B/T ratio > median in individuals with diabetes (adjusted HR 3.42; 95% CI 1.60–7.29) compared to participants without (adjusted HR 1.36; 95% CI 1.15–1.60) and the interaction analysis suggested a presence of additive interaction between IL6 trans-signalling and diabetes on the CVE risk (adjusted S=5.23; 95% CI 0.93–29.26) as seen in Figure 1.
Conclusion
Individuals with diabetes mellitus have an increased risk of CVE associated with IL6 trans-signalling possibly in part due to an additive interaction between the two.
Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): The Stockholm County Council ALF projectStrategic research in Epidemiology at Karolinska Institutet
Figure 1
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