High blood cholesterol is typically considered a feature of wealthy western countries
. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world
...and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health
. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular risk-changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have ...reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.
This study sought to test the association between the rs9349379 genotype and SCAD.
Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.
The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval CI: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.
The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
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In prior studies, stroke incidence has mainly shown either declining time trends or stable rates in high-income countries. Changes could partially be linked to trends in classic cardiovascular ...disease (CVD) risk factors. In the present study, we analyzed the incidence of stroke in parallel with the prevalence of CVD risk factors over time in a German population. Data from three independent population-based MONICA/KORA Augsburg surveys conducted in 1989/90 (S2), 1994/95 (S3), and 1999/2001 (S4) were used to calculate age-standardized incidence rates (IR) of first-ever stroke over eight years from each baseline survey. Furthermore, the age-standardized prevalence rates of CVD risk factors were analyzed for these surveys. Changes in IR or prevalence were considered significantly different if their 95% confidence intervals (CI) did not overlap. The age-standardized IR of stroke showed no significant time trend (S2: IR = 203.4 per 100,000 person-years; CI 176.4-233.4, S3: IR = 225.6; 197.1-257.0, S4: IR = 209.9; CI 182.4-240.3). In agreement, the prevalence of the CVD risk factors was quite stable over time, showing divergent, but mostly non-significant changes. However, due to the aging Western societies and the longer survival time of stroke patients, the total number of stroke patients in the population will increase even with a stable IR.
Objective To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report ...risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures.Design Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis.Results Overall, 503 905 participants aged 60 and older were included in this study, of whom 37 952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar.Conclusions Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.
Incidence of early-onset type 1 diabetes (T1D) has been increasing worldwide. Only few studies examined the relationship between geographical environmental variation and T1D incidence or its ...presymptomatic stage of islet autoimmunity. Our study aimed to investigate the effect of long-term environmental exposures during pregnancy and early life on childhood islet autoimmunity.
We used data from the Fr1da cohort study which screened children aged 1.75–5.99 years for multiple islet autoantibodies in Bavaria, Germany between 2015 and 2019. We included 85,251 children with valid residential information. Daily averages for particulate matter with a diameter <2.5 μm, nitrogen dioxide, ozone, air temperature, and greenness were averaged for each zip-code or directly assigned to the addresses. The exposure windows included pregnancy, the first year and the first two years of life. Generalized additive models adjusting for individual and socioeconomic variables were used to investigate associations between environmental exposures and islet autoimmunity development.
Islet autoimmunity was diagnosed in 272 children. Colder air temperature during pregnancy was associated with developing islet autoimmunity at the address (per 2.2 °C decrease, Odds ratio (OR): 1.49; 95% Confidence interval (CI): 1.21–1.83) and zip-code level (per 2.4 °C decrease, OR: 1.31; 95% CI: 1.08–1.59). Using the addresses, significant associations were also observed during the first years of life.
In this study, children's residential exposure to lower levels of air temperature during pregnancy and early life increased the risk of islet autoimmunity before the age of six.
•A large-scale and unselected public health cohort of children is investigated.•Air pollutants, air temperature and surrounding greenness are included.•Both address and zip code level exposures and multiple window periods are considered.•Early exposure to low air temperature increased the risk of islet autoimmunity.•Older kids or those with a diabetes family history were more susceptible.
To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and ...83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
Higher air temperature is associated with increased age-related morbidity and mortality. To date, short-term effects of air temperature on leukocyte telomere length have not been investigated in an ...adult population. We aimed to examine the short-term associations between air temperature and leukocyte telomere length in an adult population-based setting, including two independent cohorts. This population-based study involved 5864 participants from the KORA F3 (2004–2005) and F4 (2006–2008) cohort studies conducted in Augsburg, Germany. Leukocyte telomere length was assessed by a quantitative PCR-based method. We estimated air temperature at each participant′s residential address through a highly resolved spatiotemporal model. We conducted cohort-specific generalized additive models to explore the short-term effects of air temperature on leukocyte telomere length at lags 0–1, 2–6, 0–6, and 0–13 days separately and pooled the estimates by fixed-effects meta-analysis. Our study found that between individuals, an interquartile range (IQR) increase in daily air temperature was associated with shorter leukocyte telomere length at lags 0–1, 2–6, 0–6, and 0–13 days (%change: −2.96 −4.46; −1.43, −2.79 −4.49; −1.07, −4.18 −6.08; −2.25, and −6.69 −9.04; −4.27, respectively). This meta-analysis of two cohort studies showed that between individuals, higher daily air temperature was associated with shorter leukocyte telomere length.
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ...ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
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