Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans

Boua, Palwende Romuald; Brandenburg, Jean-Tristan; Choudhury, Ananyo; Sorgho, Hermann; Nonterah, Engelbert A.; Agongo, Godfred; Asiki, Gershim; Micklesfield, Lisa K.; Choma, Solomon; Gómez‐Olivé, Francesc Xavier; Hazelhurst, Scott; Tinto, Halidou; Crowther, Nigel J; Mathew, Christopher; Ramsay, Michèle; Study, AWI-Gen; Consortium, the H3Africa

doi:10.1038/s41467-022-28276-x

Cited by 13 publications

(10 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study included younger patients compared to our study, where all patients were 40 years and older; this explains why our prevalence of CA is higher than theirs. In addition, the variation in prevalence could also be explained by the genetic diversity of the African populations, where genetic associations with CIMT and its link to atherosclerosis with sexspeci c effects have been proven, especially in sub-Saharan Africans [29]. This meta-analysis, however, did not evaluate the effect of non-HDL-c/HDL-c on the CIMT, nor had it determined the predictors of CA.…”

Section: Discussionmentioning

confidence: 95%

Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda

Saasita

Kaddumukasa

Najjuma

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Type 2 diabetes mellitus (T2DM) poses an increased risk for cardiovascular disease (CVD) through atherosclerosis. The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) (ApoB/ApoA-I) ratio is a powerful predictor of atherosclerotic CVD and is associated with carotid atherosclerosis (CA) in T2DM; however, this association had never been studied in our setting. This study set out to determine the prevalence of CA and its correlation with ApoB/ApoA-I and non-high-density lipoprotein cholesterol (non-HDL-c)/high-density lipoprotein cholesterol (non-HDL-c/HDL-c) ratios among patients with T2DM in Southwestern Uganda. Methods: A cross-sectional study conducted at Mbarara Regional Referral Hospital included 212 ambulatory patients with T2DM aged ≥40 years. Socio-demographic, clinical, and behavioral characteristics were determined. Fasting blood samples were collected for measuring serum glucose, Apo B, Apo A-I, and the routine lipid profile. The apoB/apoA-I ratio and the non-HDL-c/HDL-c ratio were calculated. Carotid intima-media thickness (CIMT) was measured bilaterally at three points by high-resolution B-mode ultrasound. A mean value of six measurements from the right and left carotid arteries was used as a measure of CIMT. Carotid atherosclerosis was defined as a mean CIMT≥1.0 mm. A stepwise multivariate regression analysis and Pearson’s correlation were used to assess the association and correlation of CIMT with clinical factors, apoB/apoA-I, and non-HDL/HDL-c ratios. Results: The prevalence of CA was 35.9%. Age ≥55 years (OR 3.1; 95% CI:1.4 – 7.1; p<007) and age ≥ 65 years (OR 10.2; 95% CI: 3.5–29.5; p-< 0.001), coinfection with HIV (OR 3.8; 95% CI: 1.1–12.5; p-value = 0.030), high waist circumference (OR 2.7; 95% CI: 1.2 – 6.5; p-value = 0.022) and non-HDL-c/HDL-c ratio ≥ 4 (OR 3.0; 95% CI 1.0–8.5; p = 0.045) were associated with CA. The apoB/apoA-I ratio was elevated among T2DM patients with CA, but was not significantly associated with CA (OR 1.0; 95% CI: 0.4 – 2.5, p= 0.25). The optimal non-HDL-c/HDL-c ratio cutoff value for detecting CA was 3.39 (a sensitivity of 60.53% and a specificity of 54.41%). Conclusion: There is a high prevalence of CA among patients with T2DM. The non-HDL-c/HDL-c ratio was significantly associated with high CIMT but not the apoB/apoA-I ratio.

show abstract

Section: Discussionmentioning

confidence: 95%

Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda

Saasita

Kaddumukasa

Najjuma

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“… 28 Sex‐specific genetic effects were also considered. 29 Nevertheless, postmenopausal hormone replacement therapy was not proved to ultimately reduce the risk of atherosclerosis, which indicates biological mechanism of female hormones still needs to be further studied. 30 Iemolo et al found that sex hormones may influence the remodeling of atherosclerosis, causing more stenosis but less plaque presence in women than in men.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have confirmed that estrogen could optimize metabolism, macrophage or smooth muscle cell function, which help women to resist atherosclerosis 28 . Sex‐specific genetic effects were also considered 29 . Nevertheless, postmenopausal hormone replacement therapy was not proved to ultimately reduce the risk of atherosclerosis, which indicates biological mechanism of female hormones still needs to be further studied 30 .…”

Section: Discussionmentioning

confidence: 99%

Sex‐specific risk factors of carotid atherosclerosis progression in a high‐risk population of cardiovascular disease

Cheng

Zhou

Wang

et al. 2022

Clinical Cardiology

View full text Add to dashboard Cite

Background The progression of carotid intima‐media thickness (cIMT) and plaques are associated with cardiovascular health, especially for high‐risk population of cardiovascular disease (CVD). Hypothesis Risk factors for atherosclerosis may vary by sex. This study aimed to investigate the sex‐specific risk factors of cIMT and plaque progression. Methods We selected subjects who were identified as high‐risk population of CVD, and collected their carotid ultrasound data and baseline characteristics. Linear regression and logistic regression analyses were used to identify risk factors for cIMT and plaque progression. Sex‐specific risk factors were identified respectively. Results A total of 7908 participants were included. The mean age was 57.75 ± 9.45 years and 61.51% were female. During mean follow‐up of 1.92 ± 0.89 years, the median annual cIMT change rate was −7.25 μm/year. Seven hundred and fifteen subjects free from plaques at baseline developed plaque. Age, smoking, hypertension, and diabetes were common risk factors for carotid atherosclerosis progression in all participants. Smoking and alcohol drinking were significantly associated with increased cIMT change in women, while hypertension and antihypertensive medication were significant in men. Increased total cholesterol and diabetes were significantly associated with new plaque presence in women, while smoking, increased triglyceride, and dyslipidemia were significant in men ( p ˂ .05 for all cases). The association of baseline cIMT and smoking with annual cIMT change rate and increased total cholesterol with new plaque presence were significantly differentiated between both sexes ( p for interaction ˂ .05). Conclusions The risk factors for cIMT and plaque progression differed by sex.

show abstract

“…Testing association is a crucial part of GWAS as the positive genes are reported from this inferential procedure in a case-control study design. The contingency table tests for individual single-nucleotide polymorphism (SNP) are carried out here, where, the individual genotype counts are handled with the phenotype (case-control) [3] [5] [6] [9] [10] [11] [12]. Generally, the two degrees of freedom (d.f.)…”

Section: Introductionmentioning

confidence: 99%

On the Different Ways to Handle the Trend of Disease Risk in Genetic Association Tests

Basak¹

2022

OJS

View full text Add to dashboard Cite

Genetic association studies usually apply the simple chi-square (χ 2 )-test for testing association between a single-nucleotide polymorphism (SNP) and a particular phenotype, assuming the genotypes and phenotypes are independent. So, the conventional χ 2 -test does not consider the increased risk of an individual carrying the increasing number of disease responsible allele (a particular genotype). But, the association tests should be performed with the consideration of this disease risk according to the mode of inheritance (additive, dominant, recessive). Practical demonstration of the two possible methods for considering such order or trends in contingency tables of genetic association studies using SNP genotype data is the purpose of this paper. One method is by pooling the genotypes, and the other is scoring the individual genotypes, based on the disease risk according to the inheritance pattern. The results show that the p-values obtained from both the methods are similar for the dominant and recessive models. The other important features of the methods were also extracted using the SNP genotype data for different inheritance patterns.

show abstract

Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans

Cited by 13 publications

References 74 publications

Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda

Carotid Atherosclerosis and its Correlation with ApoB/ApoA-I and Non-HDL-c/HDL-c Ratios among Adults with Type 2 Diabetes: A Cross-Sectional Study in Southwestern Uganda

Sex‐specific risk factors of carotid atherosclerosis progression in a high‐risk population of cardiovascular disease

On the Different Ways to Handle the Trend of Disease Risk in Genetic Association Tests

Contact Info

Product

Resources

About