Age-related differences in the management and outcome of patients with acute coronary syndromes.

BACKGROUND: Age-related differences in patients with an acute coronary syndrome (ACS) have not been well characterized in prior observational studies that often included only certain age groups or subjects with myocardial infarction (MI). METHODS: We stratified 4627 patients admitted with an ACS across 9 provinces between 1999 and 2001 enrolled in the Canadian ACS Registry into 3 age groups (< 65, 65-74, and > or = 75 years) to evaluate differences in clinical characteristics, management, and 1-year outcome. RESULTS: Older patients more frequently had previous angina, MI, or heart failure and were less likely to have positive cardiac markers, ST elevation, and Q-wave MI or to receive thrombolytics, beta-blockers, and cholesterol-lowering and antiplatelet agents in hospital, at discharge, and at 1 year. In multivariable analyses controlling for patient factors, every decade increase in age was independently associated with reduced use of coronary angiography (odds ratio [OR] 0.79, 95% CI 0.74-0.84, P < .001) and percutaneous coronary intervention (OR 0.88, 95% CI 0.81-0.95, P = .001). When adjusted for validated clinical prognosticators and differences in management, every decade of age increment independently predicted an increased risk of death at 1 year (OR 1.87, 95% CI 1.66-2.12, P < .001). CONCLUSIONS: Across the broad spectrum of ACS, elderly patients had more complex comorbidities and worse outcome, yet they were less likely to undergo revascularization or to receive acute and long-term evidence-based medications. Our findings emphasize the ongoing need to better define and promote optimal therapeutic regimens for elderly patients with ACS.

Prognostic implications of prominent R wave in electrocardiographic leads V1 or V2 in patients with acute coronary syndrome.

Although the adverse prognosis of Q-waves on electrocardiogram (ECG) has been demonstrated, the prognostic significance of prominent R wave (PRW) in V1 or V2 across a broad spectrum of acute coronary syndrome (ACS) has not been specifically studied. In the Global Registry of Acute Coronary Events (GRACE) and the Canadian ACS Registry I ECG substudies, admission ECGs were analyzed in an independent core ECG laboratory. PRW was defined as R wave >40 to 50 ms in V1 or V2, R/S ≥1 in V1, or R/S ≥1.5 in V2. Among 11,895 patients with ACS, 495 (4.2%) had PRW; they were less likely to have a history of hypertension or heart failure and had lower GRACE risk scores, but a higher incidence of ST-segment depression (all p ≤0.001). Patients with PRW had similar rates of in-hospital death (2.8% vs 4.1%, respectively, p = 0.15) but lower rates of in-hospital heart failure (8.5% vs 15.2%, respectively, p = 0.02) and 6-month mortality (4.6% vs 8.4%, respectively, p = 0.004). In multivariable analyses, PRW was not a significant independent predictor of in-hospital mortality (adjusted odds ratio = 0.99, 95% confidence interval 0.55 to 1.8) or 6-month mortality (adjusted odds ratio = 0.70, 95% confidence interval 0.43 to 1.15). Among 4,418 patients who underwent coronary angiography, those with PRW had a higher prevalence of left circumflex artery disease (62.5% vs 49.5%, respectively, p = 0.01). In conclusion, across the broad spectrum of patients with ACS, PRW provides no significant additional prognostic utility beyond comprehensive risk assessment using the GRACE risk score. PRW is more frequently associated with left circumflex artery disease.

The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.

Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage.