Osteopontin gene variation and cardio/cerebrovascular disease phenotypes.

We aimed at associating common osteopontin (OPN) gene variants with cardiovascular disease phenotypes.We scanned the OPN gene in 190 chromosomes from myocardial infarction (MI) patients and identified five variants in the promoter, three synonymous and one non-synonymous variant. All variants were investigated in case-control studies for MI (ECTIM: 990 cases, 900 controls) and brain infarction (BI) (GENIC: 466 cases, 444 controls). Promoter variants were functionally analyzed by bandshift assays, the coding D147D [T/C] by Western blot. Allele D147D C was independently and significantly associated with lower apoB levels (P=0.044 [ECTIM] P=0.03 [GENIC]), its allele frequency was significantly lower in patients with BI compared to controls (OR [95% CI] 0.39 [0.20-0.74], P=0.004), and C allele carriers had a significantly lower frequency of presence of carotid plaques (P=0.02). Bandshifts with HepG2 and Ea.hy926 nuclear proteins did not reveal any functionality of promoter variants, whereas the OPN-441C-containing construct resulted in reduced OPN protein expression in Western blots, complying with its potential protective effect on the phenotypes studied.We here provide evidence that a portion of the OPN locus is likely to associate with cardiovascular disease-related phenotypes. However, further experiments are warranted to clarify the functional role of OPN variants.

Frequency and risk factors of potentially inappropriate medication use in a community-dwelling elderly population: results from the 3C Study.

OBJECTIVE: To estimate the frequency of potentially inappropriate medication use among community-dwelling elderly subjects and to identify socio-demographic factors associated with this use. METHODS: Data were collected in the Three-City Study, a French longitudinal study on vascular factors and cognitive decline. The study population was composed of 9,294 subjects aged 65 years and older, living in the community. Inappropriate medication use was assessed using a list derived from the Beers criteria by a panel of French experts. RESULTS: Nearly 40% of the participants used at least one potentially inappropriate medication: 23.4% used cerebral vasodilators, 9.2% long-acting benzodiazepines and 6.4% drugs with anticholinergic properties. Excluding cerebral vasodilators from the list, the frequency of potentially inappropriate medication use was 21.7%. This use was significantly more frequent among women, older subjects and poorly educated subjects. Adjusted analyses showed that these associations could not be explained by a confounding effect of medical factors. Compared with 13.0% of men with a high educational level, 27.9% of women with a low educational level used at least one potentially inappropriate medication (odds ratio=2.0; 95% confidence interval: 1.7-2.3). CONCLUSION: This study is the first attempt to evaluate the frequency of potentially inappropriate medication use in the elderly French population. Female gender and low socio-economic characteristics reduced the chances of receiving optimal pharmacotherapy. The proportion of elderly subjects receiving potentially inappropriate medication was higher than shown in previous studies. This is mainly explained by differences in the use of cerebral vasodilators.

Predictive values of lacunar transient ischemic attacks.

BACKGROUND AND PURPOSE: We postulated that a lacunar syndrome occurring with transient ischemic attacks (TIAs) or progressive nonsudden onset predicts a brain infarction (BI), presumably caused by a small artery disease (ie, lacunar BI) better than a lacunar syndrome with sudden onset. METHODS: We included 510 patients with BI. BI was classified into etiologic groups including lacunar BI group. We identified the patients with lacunar or nonlacunar syndrome, and those with TIAs preceding the BI or with symptoms of nonsudden onset. RESULTS: Nonlacunar syndrome had a negative predictive value for a lacunar BI of 95%. A lacunar syndrome had a positive predictive value (PPV) of 57% for lacunar infarction (n=109), and the PPV increased to 79% in the case of recent TIAs preceding the lacunar syndrome. Hypertension was present in 95% of cases with lacunar TIAs (odds ratio: 10.69; 95% confidence interval: 1.34 to 84.82; P=0.02). CONCLUSIONS: Lacunar TIAs are almost always associated with history of arterial hypertension and have a high PPV for lacunar BI. This subgroup of patients may reflect different underlying mechanisms than the group of patient with lacunar syndrome of sudden onset.

Association between influenza vaccination and reduced risk of brain infarction.

BACKGROUND AND PURPOSE: Because infections subsequent to influenza may play a role in promoting the complications of atherosclerotic disease and may also induce hypercoagulation, we hypothesized that influenza vaccination may protect against brain infarction. METHODS: During the influenza epidemic period we studied 270 subjects, including 90 consecutive patients older than 60 years admitted to the hospital for brain infarction and 180 population-based controls, matched for age, sex, and district of residency in Paris. We conducted a structured interview on whether they had been vaccinated during the last influenza vaccination campaign or every year during the 5 last years. RESULTS: We found significantly fewer vaccinated subjects during the last vaccination campaign among patients with brain infarction than among controls (46.7% versus 59.4%; P=0.036) and fewer patients vaccinated every year during the last 5 years (41.1% versus 56.1%; P=0.017). After adjustment for age, traditional risk factors, and recent use of antibiotics, the risk of stroke was reduced in the subjects vaccinated during the year of the study and in those vaccinated during the last 5 years, with an odds ratio of 0.50 (95% CI, 0.26 to 0.94; P=0.033) and 0.42 (95% CI, 0.21 to 0.81; P=0.009), respectively. Similar associations were observed in cases and controls free of previous cardiovascular history. Subjects younger than 75 years and subjects free of risk factors or in high social class were significantly less often vaccinated than controls. CONCLUSIONS: Influenza vaccination may protect against brain infarction by reducing infections or may identify a subgroup of patients at low risk for stroke because of a better lifestyle. These results give rise to a new hypothesis for research into stroke prevention.