Rome, Italy - Single-center data from a private clinical practice in the US provide support for an aggressive and comprehensive risk-factor modification program in patients with subclinical atherosclerosis. Presenting these observational data, investigators report that a global risk-factor assessment and aggressive management could reduce plaque burden and improve carotid intima-media thickness (IMT) measurements in patients with subclinical disease.

"We found not only a significant improvement in carotid IMT but also plaque reduction," said Dr Brad Bale (Heart Attack Prevention Clinic, Spokane, WA) during a presentation at the International Symposium on Atherosclerosis here today. "This latter finding was unexpected and an exciting new observation in clinical medicine indicating a regression of atherosclerosis."

Dr Terje Pedersen (Ullevål University Hospital, Oslo, Norway), the lead investigator of the IDEAL study, who was not affiliated with this present study, spoke with heartwire about the findings. While he said the data are exciting, the results should be interpreted with caution.

"This is an observational study without any control group and not randomized in any way," said Pedersen. "But the results are still interesting because they compare very well with Steven Nissen's intravascular ultrasound study (ASTEROID) that used high-dose rosuvastatin and also showed a regression of atherosclerosis."

Identifying silent vascular disease

During his presentation, Bale told the assembled audience that there is a well-documented relationship between carotid IMT and coronary heart disease. The purpose of this study was to determine whether—in a private clinical practice rather than an academic university setting—aggressive treatment would have a significant impact on the atherosclerotic disease process. All patients undergoing initial and one-year follow-up carotid IMT measurements in the clinic after November 2003 were included in this case series review.

Digital B-mode ultrasound was used to assess carotid IMT and carotid plaque in 209 patients. Patients were primarily white and middle-aged, with one third of them female. Although approximately 95% of the patients were treated for primary prevention, a majority of patients were overweight, hyperlipidemic, and hypertensive. More than half the patients met the criteria for the metabolic syndrome and approximately three quarters of patients had atherosclerosis as measured by the ultrasound.

At baseline, patients were treated with an average of three cardiovascular medications, but this was increased to five after one year. The majority of patients received combination therapy involving antiplatelet medication (88.0%), ACE inhibitors/angiotensin receptor blockers (78.0%), thiazolidinediones (TZDs) (53.4%), statin therapy (89%), extended-release niacin (65.4%), fibrates (27.0%), and ezetimibe (14%). More than three quarters of patients received combination lipid-lowering therapy.

Changes in lipid parameters

Lipid measurement (mg/dL)	Baseline	1 y	p
Total cholesterol	198	160	<0.001
Triglycerides	109	80	<0.001
HDL cholesterol	55	59	<0.001
LDL cholesterol	113	89	<0.001
Apolipoprotein B	90	77	<0.001
Non-HDL cholesterol	143	101	<0.001

In addition to significant changes in lipid parameters, other nonlipid parameters, including blood pressure and plasma C-reactive protein levels, were improved. Despite the number of medications, Bale reported that there was no deterioration in hepatic or renal function, as well as no significant alterations in glycemic status.

Regarding the effects on carotid IMT, the investigators report significant improvements in all IMT measurements. "The carotid IMT test revealed significant improvement in the atherosclerosis process, as evidenced by significant reductions in IMT, reduction in plaque number, which addresses the extent of disease, and a reduction in plaque burden, which addresses the extent and severity of disease," said Bale.

Carotid intima-media thickness results         

Parameter	Baseline	1 y	p
Common carotid IMT (mm)	0.771+0.118	0.736+0.110	<0.001
Number of plaques	2.0+1.5	1.8+2.0	<0.001
Sum of plaques (plaque burden)	4.2+3.8	3.7+3.4	<0.001

Bale added that the results of this study show that silent vascular disease can be identified before events and that aggressive management of these patients can significantly regress atherosclerosis. He added that there were no serious adverse drug events reported, but as many 20% reported minor side effects, including muscle complaints, flushing, and swelling. As to why just 65% of patients were treated with niacin, Bale explained that in the remaining third of patients, either they could not tolerate the drug or it was not medically justified.

Bale pointed out that there has been much discussion at the meeting by clinicians who advocate reducing LDL-cholesterol levels below 70 mg/dL to bring about atherosclerotic disease regression. However, "this is not necessarily so if you have a global approach to treatment," he said.

Commenting on the studies

Speaking with heartwire, Pedersen said that he would like to see more data on how the carotid IMT measurements were obtained. While Bale did present data showing that the carotid IMT measurements were performed by a private company in Salt Lake City, UT; that the IMT measurements were reproducible; and that all of the data was sent to Wake Forest University for analysis, Pedersen said the measurement is difficult to perform and mistakes can be made if the investigators are inexperienced with the technique.

"However, if the measurements taken are good, the results of this study are exciting," he said. "We're starting to see clinicians outside academic centers and outside clinical trials being able to regress atherosclerotic disease."

Also commenting on the results of the study for heartwire, Dr Heiner Bucher (University Hospital Basel, Switzerland) said the major question that needs to be asked is what the effect of such disease regression is on hard clinical end points. He said further study with long-term follow-up is needed to determine the clinical results of such an aggressive treatment strategy.