Cognitive outcomes 7.5 years after angioplasty compared with off-pump coronary bypass surgery.

Background: Off-pump coronary artery bypass grafting and percutaneous coronary intervention are both associated with cognitive decline, but limited data are available on long-term outcomes. This study compared long-term cognitive outcomes between patients managed with percutaneous coronary intervention and off-pump coronary artery bypass grafting.

Methods: A multicenter trial in the Netherlands randomized 280 patients to percutaneous coronary intervention or off-pump coronary artery bypass grafting.

ABCA1 impacts athero-thrombotic risk and 10-year survival in a contemporary secondary prevention setting.

Objectives: We prospectively investigated the effects of ATP-binding cassette protein-1 (ABCA1) variants on long-term clinical outcome in patients with coronary artery disease (CAD).

Background: ABCA1 is implicated in the etiology of atherothrombosis and may offer a target to reduce cardiovascular risk. However, the impact of ABCA1 on recurrent cardiovascular disease in a secondary prevention setting is as of yet unknown.

Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention.

Objectives: We investigated the effects of paraoxonase (PON)-1 variants on long-term clinical outcome in patients with coronary artery disease (CAD).

Background: PON-1 is a potential therapeutic target to further reduce cardiovascular risk because it is a detoxifying esterase with antioxidant properties. The PON-1 knockout models result in higher susceptibility to atherosclerosis, and PON activity contributes to cardiovascular risk in humans.

Absence of connexin 40 gene polymorphism, as a marker of undetected atrial fibrillation in patients with unexplained cerebral ischemic events.

Background: Atrial fibrillation (AF) is a major cause of cerebral infarction. Idiopathic AF is strongly associated with the human minor connexin 40 (Cx40) promotor polymorphism. We examined the prevalence of the minor Cx40 allele in patients with cerebral ischemia and no other cardiovascular disease (CVD), as an indication of underlying idiopathic AF.

PPAR gamma variant influences angiographic outcome and 10-year cardiovascular risk in male symptomatic coronary artery disease patients.

Objective: Activation of peroxisome proliferator-activated receptor (PPAR)-gamma signaling influences metabolic profiles and the propensity toward inflammation. Small-molecule stimulation of PPARgamma is investigated for secondary prevention of cardiovascular disease. The common PPARgamma Pro12Ala variant has functional and prognostic consequences.

CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction.

Aims: Inhibition of cholesteryl ester transfer protein (CETP) increases HDL-cholesterol. However, its combination with statins may increase mortality by factors incompletely understood. We previously observed that patients with intrinsically low CETP levels (carriers of the TaqIB-B2 allele) may have less benefit from statin therapy, and here tested this pharmacogenetic hypothesis on long-term outcomes.

Inflammatory gene haplotype-interaction networks involved in coronary collateral formation.

Objectives: Formation of collateral circulation is an endogenous response to atherosclerosis, and is a natural escape mechanism by re-routing blood. Inflammatory response- related genes underlie the formation of coronary collaterals. We explored the genetic basis of collateral formation in man postulating interaction networks between functional Single Nucleotide Polymorphisms (SNPs) in these inflammatory gene candidates.

Coronary collaterals improve prognosis in patients with ischemic heart disease.

Background: The recruitment of coronary collateral vessels results from an endogenous adaptation to ischemic heart disease (IHD). Presence of collaterals may exert protection at the time of acute or chronic obstructive coronary disease. The protective role of collaterals in patients with extensive coronary artery disease however, has been disputed.

Sustained suppression of peripheral blood immune functions by treatment with mycophenolate mofetil correlates with reduced severity of cardiac allograft rejection.

Background: We tested the hypothesis that sustained suppression of immune functions by mycophenolate mofetil (MMF) throughout the dosing interval reduces the severity of rejection.

Methods: Four groups of rat heart allograft recipients were treated orally daily through Day 5 with either: "low-dose" MMF, 10 mg/kg once daily (QD) or 5 mg/kg twice daily (BID); or "high-dose" MMF, 20 mg/kg QD or 10 mg/kg BID. The following were determined for all animals on Day 6: pharmacokinetics (PK, using high-performance liquid chromatography) of mycophenolic acid (MPA); pharmacodynamics (PD, by flow cytometry quantitation of whole blood mitogen-stimulated lymphocyte proliferation and expression of diverse T-cell surface activation molecules); and histologic graft rejection scores (RS).