Clinical Briefs

By Louis Kuritzky, MD

Prevalence and Extent of Atherosclerosis in Adolescents and Young Adults

The pathobiological determinants of Atherosclerosis in Youth (PDAY) Study reports atherosclerosis in 15- to 34-year-old men and women who underwent autopsy. Since fatty streaks and fibrous plaques commonly begin in this age group, the process of progressive lipid deposition, proliferation of smooth muscle, and ultimate mortal plaque rupture can be assessed in autopsy population studies.

The study included information from almost 3000 subjects, detailed primarily from pathologic evaluation of the thoracic aorta, abdominal aorta, and coronary arteries. As anticipated, the mean area involved and prevalence of atherosclerosis increased with age. The PDAY study showed that fatty streaks in the abdominal aorta and right coronary artery tend to be replaced with raised lesions like fibrous plaque and complicated atherosclerotic lesions.

Traditionally established risk factors were related to the progression from fatty streak to more complicated and more high-risk lesions. VLDL and LDL levels were directly associated with fatty streaks and raised lesions; HDL levels were indirectly associated with these lesions. Obesity, smoking, elevated glycohemoglobin levels and hypertension were all associated with the negative pathologic arterial changes in these young men and women that we see reflected later as cardiovascular mortal and morbid end points. Strong and colleagues conclude that true primary prevention of atherosclerotic disease will have to begin prior to adolescence.

Strong JP, et al. JAMA 1999;281: 727-735.

Level of Physical Activity and the Risk of Radiographic and Symptomatic Knee OA in the Elderly: The Framingham Study

Osteoarthritis (OA) of the knee has sometimes been described as "wear and tear" arthritis, alluding to the belief that joint stress induces the observed degenerative changes. Consonant with this opinion is the observation that obesity is associated with knee OA; also, some physically demanding occupations are associated with knee OA. On the other hand, long-distance runners have not been subject to increased risk of OA, and aerobic conditioning exercises have been shown to be therapeutic for knee OA.

The Framingham study began in 1948 in Framingham, MA, with a cohort of 5000 individuals. In examinations no. 18 (1983-1985) and no. 22 (1992-1993), knee radiographs were obtained.

An association between number of hours per day in heavy physical activity and radiographic evidence of knee OA was apparent in men and women; more than four hours daily heavy physical activity was associated with a greater than six-fold increased risk of radiographic knee OA. Heavy physical activity was exemplified by such activities as mowing with a nonpower mower, shoveling, digging, chopping wood, and brisk cycling. On the other hand, there was no association with light or moderate physical activity, daily amount of walking, or number of stairs climbed. Symptomatic knee OA was also associated with heavy physical activity. Obese individuals were disproportionately at high risk. McAlindon and associates conclude that elderly persons should be advised of the risks involved with heavy activity, particularly if they are obese.

McAlindon TE, et al. Am J Med 1999;106:151-157.

Sustained Release Bupropion, a Nicotine Patch, or Both for Smoking Cessation

Among the 20 million smokers who attempt cessation each year, more than 90% fail to maintain abstinence for longer than one year. Even in patients who use nicotine patches or gum, only 20-30% will remain nonsmokers long term. Seven-week courses of bupropion have demonstrated as much as 23% efficacy at 12 months for smoking cessation. In this placebo-controlled study, Jorenby and colleagues compared sustained release bupropion (n = 244), nicotine patch (n = 244), and the combination of the two (n = 245).

Bupropion was dosed at 150 mg for the first three days, followed by 150 mg bid for nine weeks; nicotine patches were dosed as 21 mg daily for six weeks, followed by 14 mg daily for one week, then 7 mg daily for one week.

Successful abstinence at one year was achieved by 35.5% of the combination therapy group, compared with 30.3% in the bupropion alone group, and 16.4% in the nicotine patch alone group.

Weight gain, a daunting deterrent to cessation for many smokers, occurred in all groups but was least in the combination treatment group (1.1 kg over 7 weeks). Adverse events caused medication discontinuation in less than 10% of subjects.

In this trial, the combination of bupropion with nicotine patches demonstrated a trend toward greater efficacy than bupropion alone, with less weight gain at seven weeks.

Jorenby DE, et al. N Engl J Med 1999;340:685-691.