scholarly journals Mendelian Randomization Analyses Suggest Childhood Body Size Indirectly Influences End Points From Across the Cardiovascular Disease Spectrum Through Adult Body Size

2021 ◽  
Author(s):  
Grace M. Power ◽  
Jessica Tyrrell ◽  
Timothy M. Frayling ◽  
George Davey Smith ◽  
Tom G. Richardson
Keyword(s):  
Cardiovascular Disease ◽  
Body Size ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Adult Body Size ◽  
Disease Spectrum ◽  
Disease Outcomes ◽  
Increased Risk ◽  
Adult Body ◽  
Artery Disease

Background Obesity is associated with long‐term health consequences including cardiovascular disease. Separating the independent effects of childhood and adulthood obesity on cardiovascular disease risk is challenging as children with obesity typically remain overweight throughout the lifecourse. Methods and Results This study used 2‐sample univariable and multivariable Mendelian randomization to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the cardiovascular disease disease spectrum. Univariable analyses identified strong evidence of a total effect between genetically predicted childhood body size and increased risk of atherosclerosis, atrial fibrillation, coronary artery disease, heart failure, hypertension, myocardial infarction, peripheral artery disease, and varicose veins. However, evidence of a direct effect was weak after accounting for adult body size using multivariable Mendelian randomization, suggesting that childhood body size indirectly increases risk of these 8 disease outcomes via the pathway involving adult body size. Conclusions These findings suggest that the effect of genetically predicted childhood body size on the cardiovascular disease outcomes analyzed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where, if ever, the detrimental impact of obesity initiated in early life begins to become immutable.

scholarly journals Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis

2021 ◽  
Author(s):  
Tom G Richardson ◽  
Juha Mykkänen ◽  
Katja Pahkala ◽  
Mika Ala-Korpela ◽  
Joshua A Bell ◽  
...  
Keyword(s):  
Body Size ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Causal Effect ◽  
Direct Effects ◽  
Metabolic Markers ◽  
Adult Body Size ◽  
Childhood Adiposity ◽  
Adult Body

Abstract Background Individuals who are obese in childhood have an elevated risk of disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independently of adult adiposity, is unclear. In this study, we have simultaneously evaluated the effects of childhood and adulthood body size on 123 systemic molecular biomarkers representing multiple metabolic pathways. Methods Two-sample Mendelian randomization (MR) was conducted to estimate the causal effect of childhood body size on a total of 123 nuclear magnetic resonance-based metabolic markers using summary genome-wide association study (GWAS) data from up to 24 925 adults. Multivariable MR was then applied to evaluate the direct effects of childhood body size on these metabolic markers whilst accounting for adult body size. Further MR analyses were undertaken to estimate the potential mediating effects of these circulating metabolites on the risk of coronary artery disease (CAD) in adulthood using a sample of 60 801 cases and 123 504 controls. Results Univariable analyses provided evidence that childhood body size has an effect on 42 of the 123 metabolic markers assessed (based on P < 4.07 × 10−4). However, the majority of these effects (35/42) substantially attenuated when accounting for adult body size using multivariable MR. We found little evidence that the biomarkers that were potentially influenced directly by childhood body size (leucine, isoleucine and tyrosine) mediate this effect onto adult disease risk. Very-low-density lipoprotein markers provided the strongest evidence of mediating the long-term effect of adiposity on CAD risk. Conclusions Our findings suggest that childhood adiposity predominantly exerts its detrimental effect on adult systemic metabolism along a pathway that involves adulthood body size.

scholarly journals Evaluating the direct effects of childhood adiposity on adult systemic metabolism: A multivariable Mendelian randomization analysis

2020 ◽  
Author(s):  
Tom G Richardson ◽  
Juha Mykkanen ◽  
Katja Pahkala ◽  
Mika Ala-Korpela ◽  
Joshua A Bell ◽  
...  
Keyword(s):  
Body Size ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Later Life ◽  
Risk Scores ◽  
Lifestyle Modifications ◽  
Adult Body Size ◽  
Childhood Adiposity ◽  
Adult Body

Background: Individuals who are obese in childhood have an elevated risk of cardiometabolic disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independent of adult adiposity, is unclear. Methods and Results: We conducted a multivariable Mendelian randomization (MR) study to simultaneously evaluate the effects of childhood and adulthood body size on over 100 systemic molecular biomarkers representing multiple metabolic pathways. We first validated UK Biobank-derived genetic risk scores using data on body mass index (BMI) measured during childhood (n=2,427, age: 3-18 years) and adulthood (n=1,762, age: 34-49 years) from the Young Finns Study (YFS). Results indicated that the childhood score is a stronger predictor of childhood BMI (0.74 vs 0.62 area under the curve (AUC) for the childhood and adult scores respectively), whereas the adult score was a stronger predictor of adulthood BMI (0.57 vs 0.62 AUC). Two-sample MR analyses in a univariable setting using summary genome-wide association study (GWAS) data in up to 24,925 adults provided evidence of an effect of childhood body size on 42 of the 123 metabolic markers assessed (based on P<4.07x10-04). Undertaking multivariable MR analyses suggested that the effects for the majority of these metabolic biomarkers (35/42) substantially attenuated when accounting for adult body size. In further analyses, the biomarkers with the strongest evidence of mediating a long-term effect of adiposity on coronary artery disease (CAD) risk were those related to triglyceride-rich very-low-density lipoprotein particles. In contrast, the biomarkers which showed the strongest evidence of being directly influenced by childhood body size (amino acids leucine, isoleucine and tyrosine) provided little evidence that they mediate this effect on adult disease risk. Conclusions: The effects of childhood adiposity on the majority of biomarkers investigated in this study were greatly attenuated when accounting for adult body size. This suggests that the detrimental impact of genetically predicted childhood adiposity on systemic metabolism, as well as subsequent later life risk of CAD, can likely be mitigated through lifestyle modifications during adolescence and early adulthood.

scholarly journals Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1644
Author(s):  
Bowen Liu ◽  
Amy M. Mason ◽  
Luanluan Sun ◽  
Emanuele Di Angelantonio ◽  
Dipender Gill ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
General Population ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Disease Outcomes ◽  
Artery Disease ◽  
Diagnosed Diabetes

(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c < 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c < 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p < 0.004, 0.05/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.

scholarly journals Additive Effects of Genetic Interleukin‐6 Signaling Downregulation and Low‐Density Lipoprotein Cholesterol Lowering on Cardiovascular Disease: A 2×2 Factorial Mendelian Randomization Analysis

2021 ◽  
Author(s):  
Marios K. Georgakis ◽  
Rainer Malik ◽  
Stephen Burgess ◽  
Martin Dichgans
Keyword(s):  
Cardiovascular Disease ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Artery Disease

Background Although trials suggest that anti‐inflammatory approaches targeting interleukin (IL)‐6 signaling can reduce cardiovascular risk, it remains unknown whether targeting IL‐6 signaling could reduce risk additively to low‐density lipoprotein cholesterol (LDL‐C) lowering. Here, we assess interactions in associations of genetic downregulation of IL‐6 signaling and LDL‐C lowering with lifetime cardiovascular disease risk. Methods and Results Genetic scores for IL‐6 signaling downregulation and LDL‐C lowering were used to divide 408 225 White British individuals in UK Biobank into groups of lifelong exposure to downregulated IL‐6 signaling, lower LDL‐C, or both. Associations with risk of cardiovascular disease (coronary artery disease, ischemic stroke, peripheral artery disease, aortic aneurysm, vascular death) were explored in factorial Mendelian randomization. Compared with individuals with genetic IL‐6 and LDL‐C scores above the median, individuals with LDL‐C scores lower than the median but IL‐6 scores above the median had an odds ratio (OR) of 0.96 (95% CI, 0.93–0.98) for cardiovascular disease. A similar OR (0.96; 95% CI, 0.93–0.98) was estimated for individuals with genetic IL‐6 scores below the median but LDL‐C scores above the median. Individuals with both genetic scores lower than the median were at lower odds of cardiovascular disease (OR, 0.92; 95% CI, 0.90–0.95). There was no interaction between the 2 scores (relative excess risk attributed to interaction index, 0; synergy index, 1; P for multiplicative interaction=0.51). Genetic IL‐6 score below the median was associated with lower cardiovascular disease risk across measured LDL‐C strata (<100 or ≥100 mg/dL). Conclusions Genetically downregulated IL‐6 signaling and genetically lowered LDL‐C are associated with additively lower lifetime risk of cardiovascular disease. Future trials should explore combined IL‐6 inhibition and LDL‐C lowering treatments for cardiovascular prevention.

Family Environment and Its Correlation with Anxiety and Depression: A Study on Heart Patients

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Dr. Meena Jain ◽  
Saloni Chandalia
Keyword(s):  
Heart Disease ◽  
Family Environment ◽  
Heart Attack ◽  
Psychiatric Symptoms ◽  
Disease Risk ◽  
Positive Association ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Increased Risk ◽  
Artery Disease

This research paper deals with the Family Environment and its Correlation with Anxiety and Depression level among persons with Heart Disease. There had been a number of researches that investigated that ischemic heart disease patients who suffer significant anxiety have close to a 5-fold increased risk of experiencing frequent angina and those with depression have more than a 3-fold increased risk for these episodes. This observed link between psychiatric symptoms and angina underlines the importance of treating anxiety and depression in cardiac patients, according to study co author Dr Mark D Sullivan (University of Washington School of Medicine, Seattle). To gather the needed data, Hamilton Anxiety Scale and Becks Depression Inventory were used. As stated from literatures, for people with heart dysfunction, depression and anxiety can increase the risk of an adverse cardiac event such as a heart attack or blood clots. For people who do not have heart disease, depression and anxiety can also increase the risk of a heart attack and development of coronary artery disease. Researchers have also emphasized on the role of family psychosocial environment and its positive association with the Coronary Heart Disease risk.

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

Grass-flower thrips of the genus Chirothrips (Thysanoptera: Thripidae), with a key to species from Iran

Zootaxa ◽  
2010 ◽  
Vol 2411 (1) ◽  
pp. 33 ◽  
Author(s):  
KAMBIZ MINAEI ◽  
LAURENCE MOUND
Keyword(s):  
Body Size ◽  
Species Group ◽  
Identification Key ◽  
Key To Species ◽  
Adult Body Size ◽  
Flower Thrips ◽  
New Synonym ◽  
Adult Body ◽  
Structural Differences

Species of the genus Chirothrips Haliday breed and pupate only within grass florets. Each larva is restricted to a single floret, and adult body size is thus presumably related to floret size. Despite this, some Chirothrips species are distinguished only on states that are related to body size. The validity of some commonly recorded members of the C. manicatus species-group, including C. africanus and C. pallidicornis, is therefore considered questionable. Character states that have been used to define the genus Agrostothrips Hood are shown to be variable, and this genus is placed as a new synonym of Chirothrips. An identification key, based on illustrated structural differences, is provided to the Chirothrips known from Iran: C. aculeatus, C. atricorpus, C. kurdistanus, C. manicatus, C. meridionalis and C. molestus.

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