Background: Hypertension, hyperlipidemia, and diabetes mellitus (DM) are common cardiovascular disease (CVD) comorbidities and well-known major determinants of atherosclerosis. However, their combined effects and relative contributions have not been well explored. This study aimed to characterize the characteristics of carotid atherosclerosis and dissect the relative effects of these common CVD comorbidities on the presence and severity of carotid atherosclerosis in community-dwelling elderly individuals. Methods: We enrolled 817 elders from communities in northern Taiwan. We evaluated their cardiovascular risk profiles and scanned their extracranial carotid arteries using high-resolution ultrasonography systems. Results: The prevalence rates for hypertension, hyperlipidemia, and DM were 45.4%, 37.1%, and 16.8%, respectively. Sixtytwo (7.6%) and 188 (23.0%) elderly had all three and two of these common CVD comorbidities, respectively. The prevalent rates of carotid plaque and moderate-to-severe atherosclerosis were 62.9% and 35.5%, respectively. The percentages of one or more common CVD comorbidities in elders with carotid plaque and moderate-to-severe atherosclerosis were 78.2% and 83.1%, respectively. Multivariate analyses showed that the number of common CVD comorbidities was the most predictive determinant. Multivariable-adjusted odds ratios (ORs) per comorbidity for the presence of carotid plaque and advanced carotid atherosclerosis were 1.52 (95% CI, 1.28-1.81) and 1.57 (95% CI, 1.28-1.93), respectively. Models containing hypertension and DM were the second most predictive. Combinatory analyses showed distinct relationship patterns between carotid atherosclerosis and hypertension, hyperlipidemia, and DM. Hypertension was significantly correlated with higher ORs for the presence of carotid plaque and advanced carotid atherosclerosis but not for hyperlipidemia. Conclusion: Carotid plaques are highly prevalent in community-dwelling elders. The number of common CVD comorbidities was the most predictive determinant of carotid plaques and advanced carotid atherosclerosis. Our results indicate that to reduce the impact of atherosclerotic diseases, blood pressure controls precede the control of blood lipids and glucose in the community-dwelling elders.
Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case–control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima–media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3′-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.
Background Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). Methods We used a case–control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10–16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. Results Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18–1.44; p = 4.7 × 10–7) and 1.47 (95% CI 1.74–9.40; p = 6.1 × 10–5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. Conclusions We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis.
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