Lipids and carotid plaque in the Northern Manhattan Study (NOMAS)

<p>Abstract</p> <p>Background</p> <p>Lipids, particularly low-density (LDL) and high-density (HDL) lipoproteins, are associated with increased risk of stroke and cardiovascular disease, probably due to atherosclerosis. The objective of this cross-sectional analysis was to investigate the relation between blood lipids and carotid plaque.</p> <p>Methods</p> <p>As part of a prospective population-based study to determine the incidence and risk factors of stroke in a multiethnic population, we evaluated 1804 participants with lipid measurements and B-mode ultrasound of carotid arteries (mean age 69 +/- 10 years; 40% men; 51% Hispanic, 26% black, 23% white). The association between lipid parameters and carotid plaque was analyzed by multiple logistic regression.</p> <p>Results</p> <p>Plaque was present in 61% of participants. Mean total cholesterol was 202 +/- 41 mg/dl. After controlling for other lipid parameters, demographics, and risk factors, the only cholesterol subfraction associated with carotid plaque was LDL (OR per standard deviation (SD) = 1.14, 95% CI 1.02-1.27). Neither HDL nor triglycerides independently predicted carotid plaque. Apolipoprotein B (ApoB) was also associated with risk of plaque (OR per SD = 1.29, 95% CI 1.03-1.60). Apolipoprotein A-I (apoA-1) was associated with a decrease in multiple plaques (OR per SD = 0.76, 95% CI 0.60-0.97), while lipoprotein a was associated with an increased risk of multiple plaques (OR per SD = 1.31, 95% CI 1.03-1.66). ApoB:ApoA-I had the strongest relation with carotid plaque (OR per SD = 1.35, 95% CI 1.08-1.69).</p> <p>Conclusions</p> <p>Among the common lipid parameters, LDL has the strongest relation with carotid plaque. Other lipid precursor proteins such as ApoB and ApoA-I may be stronger predictors of subclinical atherosclerosis, however, and better targets for treatment to reduce plaque formation and risk of cerebrovascular disease.</p

Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer cell line via up-regulation of cyclin dependent kinase inhibitor p21

Cyclooxygenase-2 is the rate-limiting enzyme in synthesis of prostaglandins and other eicosanoids. Prior reports have shown that inhibition of cyclooxygenase-2 activity, either by selective inhibitors or by antisense oligonucleotide, results in suppression of growth of squamous cell carcinoma cell lines which express high cyclooxygenase-2 levels, such as NA, a cell line established from a squamous cell carcinoma of the tongue. To investigate the mechanisms by which cyclooxygenase-2 inhibitors suppressed growth of these cells, the effects of NS-398, the selective cyclooxygenase-2 inhibitor, on cell-cycle distribution were examined. NS-398 induced G0/G1 cell-cycle arrest in NA cells which expressed cyclooxygenase-2. G0/G1 arrest induced by NS-398 was accompanied by up-regulation of cyclin-dependent kinase inhibitor p21, but not by up-regulation of the other cyclin-dependent kinase inhibitors. Transfection with p21 antisense oligonucleotide inhibited cell-cycle arrest induced by NS-398. Accumulation in G0/G1 was also observed in NA cells transfected with cyclooxygenase-2 antisense oligonucleotide. On the other hand, NS-398-treated NA cells showed a loss of plasma membrane asymmetry, a marker of early events in apoptosis. However, NS-398 did not induce other morphological and biochemical changes related to apoptotic cell death. These results suggest that cyclooxygenase-2 inhibitor induces G0/G1 cell-cycle arrest in NA cells by up-regulation of p21. Our results also suggest that NS-398 is not sufficient to complete the whole process of apoptosis in NA cells, although it induces an early event in apoptosis

Aortic atheromas and acute ischemic stroke: a transesophageal echocardiographic study in an ethnically mixed population

Proximal aortic atheromas have been suggested as a potential ischemic stroke determinant in the elderly, especially in cases of unexplained (cryptogenic) stroke. Our aim was to assess the potential role of proximal aortic atheromas as an independent risk factor for stroke by comparing their frequency in patients with acute ischemic stroke and in stroke-free control subjects. The frequency of atheromas was also compared among different ethnic groups. A case-control study was conducted in 106 patients with acute ischemic stroke and 114 stroke-free control subjects. The presence of atheromas of the proximal portion of the aorta was assessed by biplane transesophageal echocardiography. Atheromas were categorized on the basis of their thickness (0.2 to 0.4 cm, small; > or = 0.5 cm, large) and complexity (i.e., ulceration or mobility). The association between aortic atheromas and ischemic stroke was tested, controlling for patients' demographic variables and stroke risk factors. In stroke patients, subgroup analyses were performed to test the associations between aortic atheromas and stroke diagnostic subtypes (determined cause versus cryptogenic) and presence and degree of carotid stenoses by duplex Doppler examination. The frequency of large aortic atheromas was greater in stroke patients than in controls (26% versus 13%; crude odds ratio [OR] 2.4, 95% CI 1.2 to 4.7); ulcerated or mobile atheromas also tended to be more frequent in stroke patients (12% versus 5%; OR 2.5, 95% CI 1.0 to 6.8). Differences were entirely attributable to the subgroup of patients aged 60 years or older, in whom the frequency of ulcerated or mobile atheromas was particularly high among cryptogenic stroke patients (22% versus 8% in control subjects; OR 3.4, 95% CI 1.1 to 11.2). Multivariate analysis showed the presence of large atheromas to be independently associated with stroke in the entire study group (adjusted OR 2.6, 95% CI 1.1 to 5.9) and in the older subgroup (OR 2.4, 95% CI 1.1 to 5.7). Carotid stenosis > or = 60% was more frequent with increasing size and complexity of aortic atheromas but had low predictive value (16%) for presence of large atheromas; moreover, 36% of patients with mild or no carotid stenosis had large or complex aortic atheromas. No significant differences were found in the frequency of atheromas by ethnic group. Proximal aortic atheromas > or = 0.5 cm in size are a risk factor for ischemic stroke in patients aged 60 years or older. Ulcerated or mobile atheromas may play a role in explaining some cryptogenic strokes in the elderly. The risk for stroke of patients with aortic atheromas may be similar across different ethnic groups. The absence of carotid stenosis does not exclude aortic atheromas as a potential cause for ischemic stroke