| 1. |
- Della-Morte, D, et al.
(författare)
-
Association of Carotid Plaque Morphology and Glycemic and Lipid Parameters in the Northern Manhattan Study
- 2022
-
Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 9, s. 793755-
-
Tidskriftsartikel (refereegranskat)abstract
- Low Gray-Scale Median (GSM) index is an ultrasonographic parameter of soft, lipid rich plaque morphology that has been associated with stroke and cardiovascular disease (CVD). We sought to explore the contribution of the modifiable and not-modifiable cardiovascular risk factors (RFs) to vulnerable plaque morphology measured by the low GSM index. A total of 1,030 stroke-free community dwelling individuals with carotid plaques present (mean age, 71.8 ± 9.1; 58% women; 56% Hispanic, 20% Non-Hispanic Black, 22% Non-Hispanic White) were assessed for minimum GSM (min GSM) using high-resolution B-mode carotid ultrasound. Multiple linear regression models were used to evaluate the association between RFs and minGSM after adjusting for sociodemographic characteristics. Within an individual, median plaque number was 2 (IQR: 1–3) and mean plaque number 2.3 (SD: 1.4). Mean minGSM was 78.4 ± 28.7 (IQR: 56–96), 76.3 ± 28.8 in men and 80 ± 28.5 in women; 78.7 ± 29.3 in Hispanics participants, 78.5 ± 27.2 in Non-Hispanic Black participants, and 78.2 ± 29 in Non-Hispanic white participants. In multivariable adjusted model, male sex (β = −5.78, p = 0.007), obesity BMI (β = −6.92, p = 0.01), and greater levels of fasting glucose (β = −8.02, p = 0.02) and LDL dyslipidemia (β = −6.64, p = 0.005) were positively associated with lower minGSM, while presence of glucose lowering medication resulted in a significant inverse association (β = 7.68, p = 0.04). Interaction (with p for interaction <0.1) and stratification analyses showed that effect of age on minGSM was stronger in men (β = −0.44, p = 0.03) than in women (β = −0.20, p = 0.18), and in individuals not taking glucose lowering medication (β = −0.33, p = 0.009). Our study has demonstrated an important contribution of glycemic and lipid metabolism to vulnerable, low density or echolucent plaque morphology, especially among men and suggested that use of glucose lowering medication was associated with more fibrose-stable plaque phenotype (greater GSM). Further research is needed to evaluate effects of medical therapies in individuals with vulnerable, low density, non-stenotic carotid plaques and how these effects translate to prevention of cerebrovascular disease.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Liu, LL, et al.
(författare)
-
Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 6859-
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
