Arteriosclerosis, Thrombosis, and Vascular Biology Annual Conference

April 16-18, 2008 Atlanta, GA

The Arteriosclerosis, Thrombosis, and Vascular Biology Council is one of the clinical and research sections within the American Heart Association and, as the name suggests, is focused on the research and clinical developments in vascular health. Their annual meeting is sponsored by the AHA and co-sponsored by the National Heart, Blood, and Lung Institute. The program was dominated by bench and basic science research, but there were also interesting clinical and translational research presentations. Highlights from the meeting are presented below, and more conference presentations and abstracts are available at www.my.americanheart.org by following the links to conferences and education, and then to the 2008 ATVB meeting.

Women’s Vascular Health: “To HRT or Not to HRT, That Is the Question”

The large Women’s Health Initiative trial of hormone replacement therapy (HRT) in postmenopausal women indicated that HRT could be deleterious to cardiovascular health, but observational studies of women receiving HRT in perimenopausal years suggest potential benefit. There were a number of presentations at the ATVB meeting exploring this issue.

Abnormal endothelial function is a marker of vascular disease. A research group from Virginia Commonwealth University conducted an observational study on a group of postmenopausal women (N = 127; age 52-54 yr) measuring flow-mediated dilation (FMD) of the brachial artery by ultrasound as an assessment of vascular health. The subjects were categorized into four groups:

Group 1: No CVD risk factors and no HRT (n = 22)
Group 2: At least 1 CVD risk factor and no HRT (n = 47)
Group 3: At least 1 CVD risk factor plus estrogen HRT (n = 37)
Group 4: At least 1 CVD risk factor plus estrogen and progestin HRT (n = 22)

The findings indicated that FMD was improved in those women with HRT and that there was no apparent adverse effect from adding progestin to HRT. There was also a weak correlation (r = 0.32; P = 0.01) in group 1, women with no risk factors and no HRT, between decrement in FMD and increasing years since menopause. The researchers concluded that this study suggests that endothelial function is improved in postmenopausal women with risk factors for CVD when HRT is started early after menopause.

In another study, researchers from the University of Texas, Tyler, used transdermal HRT in 75 peri- and postmenopausal women after first assessing their endogenous levels of the hormones progesterone, estrogen, testosterone, and dehydroepiandrostenedione. They titrated replacement to achieve age-adjusted physiologic ranges for each of the four hormones. Twelve-month measurements compared to baseline showed improvement in C-reactive protein (P = 0.02), systolic blood pressure (BP) (P = 0.001), diastolic BP (P = 0.02), blood glucose (P = 0.001), triglycerides (P = 0.001), Greene Climacteric Scale (P = 0.002), and Hamilton Anxiety Scale (P = 0.001). There were no adverse events associated with HRT. The researchers concluded that an individualized approach to replacing sex hormones to physiologic levels in women at menopause can improve cardiovascular health and improve general well being.

Three studies looking at CVD risk assessment in postmenopausal women were presented. The Framingham Heart Study CVD risk scoring system has been criticized for not being as accurate in assessing women’s risk since it doesn’t take into account variables associated with hormone changes. A study from the Mayo Clinic, Rochester, MN, studied 102 perimenopausal women and found that 40% of the women in the cohort had abnormal or at least questionable FMD, and their Framingham risk scores were no different than the rest of the group who had normal FMD. Researchers concluded that FMD may be a useful additional measure in risk assessment in perimenopausal women, and may help identify those in whom HRT may be beneficial. In another study, 143 postmenopausal women (age 47-86 yr) were studied with black-blood magnetic resonance imaging (MRI) of the aorta and carotid arteries. They also had Framingham risk score assessment. The cohort was separated into two groups, CVD present or not, based on CVD evidence as measured by arterial wall thickness. The Framingham risk scores did not differentiate between those women who had imaging evidence of CVD and those who did not. The researchers concluded that the extra-coronary vascular MRI parameters are useful in identifying women who have CVD that may not be identified by the usual risk scoring algorithms. A third study of 47 women (average age, 65 yr) using dual energy x-ray absorptiometry scans to measure bone mineral density and carotid ultrasound to measure carotid intimal-medial thickness demonstrated a negative correlation between carotid disease and bone density, even after adjusting for other CVD risk factors. Thus, they concluded that women with bone mineral loss are at increased risk for vascular disease.

Niacin: No Flush = No Good

Niacin or nicotinic acid is one of the oldest lipid-lowering agents. It has a favorable profile of effects on dyslipidemias (increases high-density lipoprotein [HDL], decreases low-density lipoprotein [LDL], triglycerides, and Lpa), and it is relatively inexpensive. Niacin’s side-effect profile, however, especially the frequency of flushing and itching, has been a major deterrent to more widespread use. Health food stores and some vitamin companies have promoted a niacin alternative, inositol hexanicotinate (IHN), also called “no-flush” niacin. IHN does indeed have six molecules of nicotinic acid for each molecule of IHN and does not cause flushing, but it had never been studied in human clinical trials. Researchers from the University of Minnesota reported a 6-week clinical trial (N = 120) comparing IHN 1500 mg/day to 1500 mg/day of a wax-matrix sustained-release niacin, and placebo control. The sustained-release niacin was well tolerated (only 1 dropout) and resulted in significant lipid improvements: LDL = -18% (P < 0.001), HDL = +12% (P < 0.001), but the IHN and placebo were essentially identical with no significant change from baseline. The study concluded that although IHN is well tolerated (no-flushing), it has no benefit in managing dyslipidemia, and patients should be cautioned not to substitute IHN for other niacin products.

Naproxen and Low-Dose Aspirin

Many patients who are taking low-dose aspirin (ASA) as recommended for prevention of vascular thrombosis also have arthritis and may be taking various over-the-counter remedies for their joint symptoms. Investigators from Chieti, Italy, reported a pilot study looking at the possible interaction of naproxen with ASA. Normal subjects (N = 6) received three 6-day treatments each separated by a 14-day washout:

•Naproxen 220 mg twice daily, with one of the doses 2 hours before ASA 100 mg daily
•Naproxen 220 mg twice daily, with one of the doses 2 hours after ASA 100 mg daily
•ASA 100 mg alone

Platelet cyclooxygenase-1 (COX-1) activity (serum thromboxane) and platelet aggregation were measured on day 6 of treatment and the day after treatment. Aspirin alone showed a profound reduction in platelet COX-1 activity (99% reduction in serum throboxane) and only a slightly less reduction in that effect when naproxen was given with the ASA (95-98% reduction). However, when naproxen was given with ASA there was a rapid recovery of platelet aggregation as measured by arachidonic acid and collagen induction in platelet-rich plasma. Thus, researchers concluded that naproxen interferes with the irreversible inhibition of platelet aggregation function of ASA. These findings need to be studied in a larger trial, but do suggest that persons taking low-dose ASA may want to avoid the use of naproxen.

Novel Screening Test for CVD Risk

Skin sterols (SS) have been shown in previous studies to be independently associated with other markers of CVD risk in persons with coronary disease, including coronary lesions on angiography, carotid intimal-medial thickness, and coronary calcium scores. Researchers screened a population of insurance applicants (N = 9055) using Framingham risk scores, total cholesterol (TC)/HDL ratio, and highly-sensitive C-reactive protein (hsCRP) levels, as well as SS measurement to determine whether there was a correlation between SS and these other commonly accepted risk markers. The subjects were generally low-risk for CVD, Framingham global risk score = 1%, median age was 36, and 50% were female. The SS samples were obtained from a simple tape strip applied to the palm of the hand. Subjects in the highest quartile of SS (> 0.199) showed a significantly higher TC/HDL ratio (> 5) (odds ratio, 1.4; P < 0.001), and a significantly higher hsCRP level (> 3.6 mg/L) (odds ratio, 1.35; P < 0.001). Researchers concluded that this simple non-invasive test may be useful in screening low-risk populations to identify persons who may benefit from further risk factor assessment.