scholarly journals Leveraging Genetic Data to Elucidate the Relationship Between COVID‐19 and Ischemic Stroke

2021 ◽  
Author(s):  
Verena Zuber ◽  
Alan Cameron ◽  
Evangelos P. Myserlis ◽  
Leonardo Bottolo ◽  
Israel Fernandez‐Cadenas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Ischemic Stroke ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
The Relationship

Background The relationship between COVID‐19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID‐19, defined as hospitalization with COVID‐19 requiring respiratory support or resulting in death. Cross‐trait linkage disequilibrium score regression was used to estimate genetic correlations of critical COVID‐19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both COVID‐19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C‐reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical COVID‐19 was associated with increased risk of any cardiovascular outcome for which genetic correlation was identified. There was evidence of genetic correlation between critical COVID‐19 and ischemic stroke (r g =0.29, false discovery rate [FDR]=0.012), body mass index (r g =0.21, FDR=0.00002), and C‐reactive protein (r g =0.20, FDR=0.00035), but no other trait investigated. In Mendelian randomization, liability to critical COVID‐19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical COVID‐19 liability 1.03, 95% CI 1.00–1.06, P ‐value=0.03). Similar estimates were obtained for ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking, and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical COVID‐19. Conclusions These data support that liability to critical COVID‐19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe COVID‐19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.

scholarly journals Leveraging genetic data to elucidate the relationship between Covid-19 and ischemic stroke

2021 ◽  
Author(s):  
Verena Zuber ◽  
Alan Cameron ◽  
Evangelos P. Myserlis ◽  
Leonardo Bottolo ◽  
Israel Fernandez-Cadenas ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Ischemic Stroke ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk ◽  
The Relationship ◽  
Randomization Analysis

AbstractBackgroundThe relationship between coronavirus disease 2019 (Covid-19) and ischemic stroke is poorly defined. We aimed to leverage genetic data to investigate reported associations.MethodsGenetic association estimates for liability to Covid-19 and cardiovascular traits were obtained from large-scale consortia. Analyses primarily focused on critical Covid-19, defined as hospitalization with Covid-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical Covid-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both Covid-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical Covid-19 was associated with increased risk of any of the cardiovascular outcomes for which genetic correlation was identified.ResultsThere was evidence of genetic correlation between critical Covid-19 and ischemic stroke (rg=0.29, FDR p-value=4.65×10−3), body mass index (rg=0.21, FDR-p-value=6.26×10−6) and C-reactive protein (rg=0.20, FDR-p-value=1.35×10−4), but none of the other considered traits. In Mendelian randomization analysis, liability to critical Covid-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical Covid-19 liability 1.03, 95% confidence interval 1.00-1.06, p-value=0.03). Similar estimates were obtained when considering ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical Covid-19.ConclusionsThese data support that liability to critical Covid-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe Covid-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.

Serum C reactive protein levels and genetic variation in the CRP gene are not associated with the prevalence, incidence or progression of osteoarthritis independent of body mass index

2010 ◽  
Vol 69 (11) ◽  
pp. 1976-1982 ◽  
Author(s):  
Hanneke J M Kerkhof ◽  
Sita M A Bierma-Zeinstra ◽  
Martha C Castano-Betancourt ◽  
Moniek P de Maat ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Mass Index ◽  
Genetic Variation ◽  
Body Mass ◽  
Analysis Of Covariance ◽  
C Reactive Protein ◽  
Knee Oa ◽  
Reactive Protein ◽  
Serum Crp ◽  
The Relationship

ObjectiveTo study the relationship between serum C reactive protein (CRP) levels, genetic variation in the CRP gene and the prevalence, incidence and progression of radiographic osteoarthritis (ROA) in the Rotterdam Study-I (RS-I). A systematic review of studies assessing the relationship between osteoarthritis (OA) and CRP levels was also performed.MethodsThe association between CRP levels and genetic variation in the CRP gene and ROA was examined in 861 patients with hand OA, 718 with knee OA, 349 with hip OA and 2806 controls in the RS-I using one-way analysis of covariance and logistic regression, respectively. PubMed was searched for articles published between January 1992 and August 2009 assessing the relationship between CRP levels and OA.ResultsIn RS-I the prevalence of knee OA, but not hip OA or hand OA, was associated with 14% higher serum CRP levels compared with controls (p=0.001). This association disappeared after adjustment for age and especially body mass index (BMI) (p=0.33). Genetic variation of the CRP gene was not consistently associated with the prevalence, incidence or progression of OA within RS-I. The systematic review included 18 studies (including RS-I) on serum CRP levels and the prevalence, incidence or progression of OA. Consistently higher crude CRP levels were found in cases of prevalent knee OA compared with controls. No association was observed between serum CRP levels and the prevalence of knee OA following adjustment for BMI (n=3 studies, meta-analysis p value=0.61).ConclusionThere is no evidence of association between serum CRP levels or genetic variation in the CRP gene with the prevalence, incidence or progression of OA independent of BMI.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

scholarly journals The Relationship Between C-Reactive Protein and Atherosclerosis Differs on the Basis of Body Mass Index

2012 ◽  
Vol 60 (13) ◽  
pp. 1148-1155 ◽  
Author(s):  
Nitin K. Gupta ◽  
James A. de Lemos ◽  
Colby R. Ayers ◽  
Shuaib M. Abdullah ◽  
Darren K. McGuire ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
The Relationship

scholarly journals C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization

2010 ◽  
Vol 35 (2) ◽  
pp. 300-308 ◽  
Author(s):  
N J Timpson ◽  
B G Nordestgaard ◽  
R M Harbord ◽  
J Zacho ◽  
T M Frayling ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Direction Of Causation

Interactions between C-reactive protein and traditional risk factors in predicting mortality of older adults

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Henrik Rudolf ◽  
Naemi Wall ◽  
Renate Klaassen-Mielke ◽  
Ulrich Thiem ◽  
Curt Diehm ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Older Adults ◽  
Body Mass Index ◽  
Body Mass ◽  
Hazard Ratio ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
All Cause Mortality ◽  
High Level

Abstract. Background: Elevated levels of C-reactive protein (CRP) are known to be associated with cardiovascular (CV) morbidity and mortality in older adults, however, there seems to be heterogeneity of this association across subsets of individuals. We aim to assess the effects of interactions between CRP and one of the following traditional CV risk factors regarding all-cause mortality in unselected elderly men and women: age, sex, body mass index, diabetes, and hypertension. Patients and methods: Three hundred and forty-four general practitioners all over Germany enrolled 6,817 unselected participants, aged 65 years or older, and performed thorough examinations, including CRP measurement at baseline (getABI study). All-cause mortality was determined in the following seven years. Cox regression analyses were done using uni- and multivariable models. Results: At baseline 4,172 participants of this cohort had a CRP value of ≤ 3 mg/L (low level CRP group), 2,645 participants had a CRP value of > 3 mg/L (high level CRP group). The unadjusted hazard ratio for all-cause death of the high level CRP group compared to the low level CRP group was 1.49 (95 % confidence interval [95 %CI] 1.34 to 1.66). After adjustment for sex, age, education, peripheral artery disease/media sclerosis, other prior vascular events, smoking status, diabetes, systolic blood pressure, antihypertensive medication, body mass index, cholesterol, and statin use, the hazard ratio was 1.34 (95 %CI 1.20 to 1.50). Significant interactions with CRP were found for sex (adjusted hazard ratio 1.38, 95 %CI 1.11 to 1.72), age (0.75, 95 %CI 0.60 to 0.94), and baseline systolic blood pressure (0.64, 95 % CI 0.51 to 0.81). The interactions of CRP with body mass index and of CRP with diabetes were not significant. Conclusions: In older German adults, there seem to be effect modifications by age, sex, and arterial hypertension regarding the effect of CRP in the prediction of all-cause mortality.

Serum C-reactive protein levels and body mass index in children and adolescents with CHD

2016 ◽  
Vol 27 (6) ◽  
pp. 1083-1089 ◽  
Author(s):  
Maíra Ribas Goulart ◽  
Daniela Schneid Schuh ◽  
David W. Moraes ◽  
Sandra Mari Barbiero ◽  
Lucia Campos Pellanda
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Children And Adolescents ◽  
Body Mass ◽  
Heart Defects ◽  
Body Mass Index Percentile ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Significant Difference

AbstractBackgroundThe prevalence of overweight in children with CHD is about 26.9%. Increase in adipose tissue is related to the secretion of proinflammatory markers such as C-reactive protein. Assuming that children with CHD are exposed to other inherent risk factors for heart disease, our objective was to evaluate the correlation between levels of C-reactive protein and body mass index in children and adolescents with CHD.MethodsA cross-sectional study with 377 children and adolescents with CHD in a clinical setting of a reference hospital was carried out. C-reactive protein data were collected after 12 hours of fasting. Nutritional status was classified according to body mass index. The patients were divided into three groups: cyanotic, acyanotic, and minimal heart defects (controls).ResultsThe mean age was 9.9±4.2 years, and 53.6% of the sample included males. The cyanotic group represented 22.3%, acyanotic 42.2%, and minimal defects 35.5% of the sample. The average body mass index percentile was 57.23±32.06. The median values of C-reactive protein were as follows: cyanotic 0.340, acyanotic with clinical repercussion 0.203, and minimal defects 0.128. There was a significant difference between the minimal defects and the cyanotic groups (p=0.023). There was a significant correlation between C-reactive protein and body mass index percentile (r=0.293, p<0.01). C-reactive protein levels were higher in girls (p=0.034). There were no significant correlations between C-reactive protein and age or birth weight.ConclusionThe correlation between body mass index percentile and C-reactive protein was confirmed in this population. The prevention of overweight is paramount to avoid overlapping modifiable risk factors to those already inherent to the CHD.

scholarly journals Associations Between Anti-Mullerian Hormone and Cardiometabolic Health in Reproductive Age Women Are Explained by Body Mass Index

2019 ◽  
Vol 105 (3) ◽  
pp. e555-e563 ◽  
Author(s):  
Julie S Rios ◽  
Eleni A Greenwood ◽  
Mary Ellen G Pavone ◽  
Marcelle I Cedars ◽  
Richard S Legro ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Fasting Insulin ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
The Relationship ◽  
Total P

Abstract Context The relationship between reproductive and cardiometabolic aging is unclear. It is unknown if the relationship differs across different clinical populations. Objective To determine whether markers of ovarian reserve are associated with cardiometabolic risk in reproductive aged women with unexplained infertility (UI), polycystic ovary syndrome (PCOS), and regularly cycling women (OVA). Design and setting Cross-sectional data from 8 US-based academic centers. Participants Women aged 25–40 from 3 clinical populations: 870 with UI, 640 with PCOS, and 921 community-based OVA. Main Outcome Measures Multivariable linear regression models were used to relate anti-mullerian hormone (AMH) and antral follicle count with cardiometabolic parameters including body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment-insulin resistance (HOMA-IR), lipids, and C-reactive protein. Results In age and study site-adjusted models, AMH inversely related to BMI in the UI and OVA groups (P = 0.02 and P &lt; 0.001). Among women with PCOS, AMH inversely related to BMI (P &lt; 0.001), and also to WC (P &lt; 0.001), fasting insulin (P &lt; 0.01), HOMA-IR (P &lt; 0.01), triglycerides (P = 0.04), and C-reactive protein (P &lt; 0.001) and directly related to higher total (P = 0.02), low-density lipoprotein (P &lt; 0.01), and high-density lipoprotein cholesterol (P &lt; 0.01). In OVA, AMH also varied inversely with WC (P &lt; 0.001), fasting insulin (P = 0.02), and HOMA-IR (P = 0.02). Adjustment for BMI eliminated associations in the OVA group but in PCOS, the relationship of AMH to total (P = 0.03) and low-density lipoprotein cholesterol (P = 0.003) remained. Conclusion Associations observed between AMH and cardiometabolic indices are largely explained by BMI in women with and without PCOS. (J Clin Endocrinol Metab XX: 0-0, 2019)

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