Effects of Low-Dose Atorvastatin on Arterial Stiffness and Central Aortic Pressure Augmentation in Patients With Hypertension and Hypercholesterolemia.

1. Aggeliki I. Kanaki¹, Pantelis A. Sarafidis¹, Panagiotis I. Georgianos¹, Konstantinos Kanavos¹,
2. Ioannis M. Tziolas¹, Pantelis E. Zebekakis¹ andAnastasios N. Lasaridis¹

+ Author Affiliations

1. ¹Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA University Hospital, Thessaloniki, Greece.

1. Correspondence: Pantelis A. Sarafidis (psarafidis11@yahoo.gr).

• Received September 20, 2012.
• Revision received December 4, 2012.
• Accepted December 16, 2012.

Abstract

Background Experimental and clinical data suggest that statins exert anti-inflammatory and antiproliferative actions on vasculature beyond their lipid-lowering properties. Whether these pleiotropic effects of statins translate into a beneficial effect on arterial stiffness is not clear. This study aimed to evaluate the potential effects of low-dose atorvastatin treatment on arterial stiffness and central arterial pressure waveforms in patients with mild hypertension and hypercholesterolemia.

Methods In a double-blind, randomized, placebo-controlled fashion, 50 hypertensive and hypercholesterolemic patients were allocated to receive 10mg of atorvastatin or placebo for 26 weeks. Arterial stiffness was assessed by aortic pulse-wave velocity (PWV) using a Sphygmocor device. Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate–adjusted augmentation index (AIx(75)) was used as measure of wave reflections.

Results At study end, aortic PWV (9.0±1.5 vs. 10.9±2.6 m/sec; P<0 .001="" 11.8="" 28.8="" 9.7="" aix="" and="" em="" vs="">P

< 0.001) were significantly lower in the atorvastatin group than that placebo group. Furthermore, decreases in central aortic systolic blood pressure and pulse pressure were evident at study-end with atorvastatin but not with placebo (130±8 vs. 138±6mm Hg, P < 0.001; 48±7 vs. 53±6mm Hg, P < 0.05, respectively). Atorvastatin-induced reductions in aortic PWV during follow-up showed significant associations with changes in AIx(75) and central aortic systolic blood pressure and pulse pressure.

Conclusions This study shows that low-dose atorvastatin treatment improves arterial stiffness and exerts a reduction on central aortic pressures. These effects may represent a potential mechanism of cardiovascular risk reduction observed with statin use.

Clinical Trial Registration ClinicalTrials.gov Database Identifier Number: NCT01126684

Stopping aspirin after ulcer bleeding: More risk than benefit

When patients with coronary artery disease or cerebrovascular disease develop GI bleeding and undergo endoscopic therapy, a question that most gastroenterologists face is whether aspirin, clopidogrel, or both should be restarted, and if so, when. Many of these patients are at high risk for bleeding-related complications due to advanced age and comorbidities and are also at increased risk for cardiovascular or cerebrovascular complications due to advanced vascular disease. 
There are four possible courses of action for the practitioner: Discontinue the aspirin and clopidogrel with no intent to resume them, discontinue aspirin and resume clopidogrel, resume both antiplatelet drugs after endoscopic hemostasis is achieved, or withhold antiplatelet drugs for 7-10 days after endoscopic hemostasis has been achieved.
Although we do not have a complete and valid evidence base to guide our current practice, several important points can be made from recent studies. Ms. Derogar and her colleagues show us that discontinuing aspirin completely is associated with a high rate of death or cardiovascular complications. Rebleeding, on the other hand, was rare patients in whom aspirin was continued. In a recent randomized controlled trial, patients on low-dose aspirin who developed a GI bleed were randomized to continued aspirin or no aspirin after endoscopic hemostasis (Ann. Intern. Med. 2010;152:1-9). Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group. Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%). Other studies have shown that resuming aspirin with a proton pump inhibitor is superior to administering clopidogrel alone.
There is little evidence to guide us as to whether aspirin or clopidogrel should be held for a short period of time or resumed immediately after endoscopic hemostasis is achieved. This decision should probably be individualized based on the magnitude of the bleeding, the severity of the underlying cardiovascular and cerebrovascular disease, and concurrent comorbid illnesses. The available evidence is clear that it is unwise to discontinue aspirin in patients receiving this agent for cardiovascular or cerebrovascular disease due to the high rate of adverse outcomes.
Nimish Vakil, M.D., AGAF, is a clinical professor of medicine at the University of Wisconsin School of Medicine and Public Health, Madison. He is a consultant to AstraZeneca, Takeda, Otsuka, Xenoport, Orexo, Ironwood, and Restech, and has stock options in Orexo and Meridian Bioscience.

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

Bernhard Meier, M.D., Bindu Kalesan, Ph.D., Heinrich P. Mattle, M.D., Ahmed A. Khattab, M.D., David Hildick-Smith, M.D., Dariusz Dudek, M.D., Grethe Andersen, M.D., Reda Ibrahim, M.D., Gerhard Schuler, M.D., Antony S. Walton, M.D., Andreas Wahl, M.D., Stephan Windecker, M.D., and Peter Jüni, M.D. for the PC Trial Investigators

N Engl J Med 2013; 368:1083-1091March 21, 2013DOI: 10.1056/NEJMoa1211716

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Background

The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale. We investigated whether closure is superior to medical therapy.

Methods

We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil, and Australia in which the assessors of end points were unaware of the study-group assignments. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy. The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.

Results

The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence interval [CI], 0.24 to 1.62; P=0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20; 95% CI, 0.02 to 1.72; P=0.14), and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P=0.56).

Conclusions

Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT00166257.)