Atherosclerosis. Supplements最新文献

Background and aims

Hippocampal calcification is a recently described type of intracranial calcification and might be a risk factor for ischemic stroke and dementia. Data on its risk factors and insight into the etiology are limited. We aimed to investigate the association of risk factors for hippocampal calcification in two independent cohorts in the Netherlands.

Methods

Unenhanced CT scans of the brain were scored for the presence and severity of hippocampal calcification in two independent prospectively collected patient cohorts, the first consisting of aneurysmal subarachnoid hemorrhage (SAH) patients (N = 741) and the second of patients participating in the Second Manifestation of ARTerial disease (SMART) study (N = 498). We estimated the association of the risk factors age, sex, smoking, dyslipidemia, overweight, hypertension, diabetes, family history, cardiac history, cerebrovascular history, use of vitamin K antagonists and renal disease with the presence and moderate/severe calcification using logistic regression analysis.

Results

In both cohorts, age ≥60 years was associated with the presence of hippocampal calcification (odds ratio (OR) 2.47, 95% confidence interval (CI) 1.37–4.45 in SAH and OR 1.91, 95% CI 1.30–2.82 in SMART); in SMART, age was associated with moderate/severe calcification as well (OR 2.77, 96%CI 2.77 (1.36–3.65). All other risk factors, including a cumulative risk score of 5 or more risk factors, did not show any association with hippocampal calcification presence or severity.

Conclusions

We identified age as a risk factor for hippocampal calcification. All other risk factors studied were not associated with hippocampal calcification. This contradicts findings on arterial calcifications elsewhere in the body. Therefore, more research is needed to understand this discrepancy.

A key strategy in preventing cardiovascular (CV) disease is the reduction of low-density lipoprotein cholesterol (LDL-C). Statins are a crucial therapy for achieving LDL-C reductions, with the highest tolerated dose often prescribed, especially for patients who are at the greatest risk of CV disease. However, statin intolerance, heterogeneous responses to statins and non-adherence make alternative therapies necessary in some cases. Statins can be combined with a multitude of therapies with synergistic mechanisms of action to effectively manage lipid profiles, while improving safety and tolerability profiles. Addition of a cholesterol absorption inhibitor, bile acid sequestrant or fibrate to statin therapy leads to greater numbers of patients achieving and maintaining LDL-C goals. Furthermore, combination therapies can alter the plasma profiles of other molecules involved in hypercholesterolaemia, including triglycerides and high-density lipoprotein cholesterol. An additional strategy is proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition therapy, for use in patients who are statin intolerant, patients with heterozygous or homozygous familial hypercholesterolaemia, and patients at very high CV risk, as a potential means for achieving large LDL-C reductions and maintaining LDL-C goals. Clinical trials have demonstrated that PCSK9 inhibition therapy is not only effective but can also be combined with statin therapy to ensure greater reductions in LDL-C. Current, ongoing studies are investigating the efficacy of novel therapies, including selective peroxisome proliferator-activated receptor (PPAR) alpha modulators, PCSK9-specific ribonucleic acid (RNA) interference and anti-inflammatory therapies.

Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm.

Aortic endothelial cells were isolated from aortic tissue of patients with thoracic aortic aneurysm and healthy donors. Gene expression of Notch and related BMP and WNT/β-catenin pathways was estimated by qPCR; WNT/β-catenin signaling was studied by TCF-luciferase reporter. To study the stress-response the cells were subjected to laminar shear stress and the expression of corresponding genes was estimated by qPCR.

Analyses of mRNA expression of Notch genes, Notch target genes and Notch related pathways showed that endothelial cells of aneurysm patients have dysregulated Notch/BMP/WNT pathways compared to donor cells. Activity of Wnt pathway was significantly elevated in endothelial cells of the patients. Cells from patients had attenuated activation of DLL4, SNAIL1, DKK1 and BMP2 in response to shear stress.

In conclusion endothelial cells of the patients with thoracic aortic aneurysm have dysregulated Notch, BMP and WNT/β-catenin related signaling. Shear stress-response and cross-talk between Notch and Wnt pathways that normally ensures aortic integrity and resistance of endothelial cells to stress is impaired in aneurysmal patients.

We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis.

The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality.

A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study). Sample of ESSE-RF study had slightly more diabetic and hypertensive individuals, while the percentage of subjects with high cholesterol value was lower than in the other sample (67.1% vs 79.9%). The median LDL-C value was higher among individuals not treated with statins in the PLIC sample (p < 0.001), while was comparable among subjects receiving statin therapy. On the other hand, the percentage of individuals with positive cardiovascular history was higher in ESSE-RF sample. This could also explain the higher mean IMT value (0.71 ± 0.17 vs 0.63 ± 0.13) in the whole sample, and among patients without past cardiovascular events (regardless of statin treatment), despite some differences in major risk factors.

Despite Russian and Italian populations are culturally and geographically different, they are not so different based on characteristics analyzed.