Physicians’ Health Study

The third study was the Physicians Health Study, in which 22,071 US male physicians were randomised to get either 50 mg P-carotene or 325 mg aspirin, or both, or neither, every other day for 12 years. There was no evidence of a significant beneficial or harmful effect on cancer or cardiovascular... 

ATBC = Alpha Tocopherol Beta Carotene Prevention Study CARET = The Beta Carotene and Retinol Efficacy Trial PHYS = Physicians Health Study. 

Data concerning gastric cancer are scarce. The prospective Netherlands Cohort Study found no correlation between lutein dietary intake and gastric cancer risk, whereas findings from the Physicians Health Study and the ATBC study reported no effect of P-carotene on gastric cancer incidence. Two case-control studies and three intervention trials (ATBC, CARET, and the Physicians Health Study ) showed no association of P-carotene, lycopene, lutein, zeaxanthin, and P-cryptoxanthin. 

However, intervention trials investigating the effects of P-carotene and lycopene supplementation on CVD have not reported convincing results (Table 3.1.3). Among the seven studies reviewed herein, four primary prevention trials, namely the Multicenter Skin Cancer Prevention Study, the Beta Carotene and Retinol Efficacy Trial, the ATBC cancer prevention study, " and the Physicians Health Study have shown no association between a supplementation of P-carotene and risk of death from CVD or fatal and non-fatal MI. 

Epidemiological data on carotenoids and cerebral infarcts or strokes indicate a protective effect of P-carotene and lycopene. Indeed, the Basel prospective study, the Kuopio Ischaemic Heart Disease Risk Factor study, and the Physicians Health Study " have shown an inverse correlation between carotenoid plasma level and risk of stroke. In the same way, Hirvonen et al. demonstrated, in findings from the ATBC cancer prevention stndy, an inverse association between P-carotene dietary intake and stroke. However, clinical data on carotenoids and stroke are nonexistent and they are needed to confirm this possible protective effect of carotenoids on stroke. 

Sturner T, Glynn RJ, Lee IM, et al. Aspirin use and colorectal cancer post-trial follow-up data from the Physicians Health Study. Ann Intern Med 1998 128 713-720. 

In a prospective nested case-control study on physicians diagnosed with Ml who were part of the Physician Health Study (PHS) (39) in the United States, plasma levels of all carotenoids (a-carotene, /3-carotene, /3-cryptoxantin, lutein, and lycopene), retinol, and a- and y-tocopherol were analyzed. No differences were noted by the physicians between the patients diagnosed with Ml and the matched controls (40),... 

Goldhaber SZ, Manson JE, Stampfer MJ, et al. Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians Health Study. Lancet 1992 340 143-145. 

Steering Committee of the Physicians Health Study Research Group. Final report on the aspirin component of the ongoing Physicians Health Study. N Engl J Med 1989 321 129-35. 

A irin has been shown to reduce die risk of a first myocardial inferction in patients with chronic stable angina in two studies, hi the first (a subgroup of the Physicians Health Study referenced above) there was a risk reduction at least as significant as that for the healfoy men emolled in the same trial (42). In the second randomized trial of 2,035 patients, there was a 34% reduction in the incidence of first myocardial induction and sudden cardiac death associated with aspirin (43). 

One case-control study showed no increased risk of intracerebral hemorrhage in patients using aspirin or other NSAIDs in low dosages as prophylaxis against thrombosis (21). However, intracerebral hemorrhage has been reported with aspirin, even in low doses, and in the SALT study (22) and the Physicians Health Study of 1989 (23) hemorrhagic stroke and associated deaths occurred with aspirin. 

In the first study, 4425 patients hospitalized with acute myocardial infarction who used NSAIDs were compared with 17 700 controls in a large health-care database in the USA (51). Multivariate models were constructed to control for potential confounders. A quarter of the cases and controls had also filled a prescription for an NSAID in the 6 months before the study. Overall, the NSAID users had the same risk of acute myocardial infarction as non-users, but naproxen users had a significantly lower risk of acute myocardial infarction compared with those who were not taking NSAIDs (adjusted OR = 0.84 95% Cl = 0.72, 0.98). The cardioprotective effect of naproxen was very modest compared with aspirin (a 44% reduction in the risk of acute myocardial infarction in the Physician Health Study (54)). 

Three observational studies using national cohorts have examimed the risk of deteriorating renal function with chronic NSAID exposure. Two of the reports in-volvedata from the Physician Health Study [99A, 99B] while the third involved the nurses from the National Health Survey [99C]. After adjusting for confounding risk factors none of the studies identified an increase risk of loss of renal function with moderate NSAID intake. More recently Ibanez et al [99D] conducted a 2 year case control study regarding the relative risk of ESRD associated with NSAIDs. They reported a Odd Ratio of 1.22 (CL 0.89-1.66) for the risk of ESRD associated with NSAIDs. 

Christen WG, Gaziano J, Hennekens CH. 2000. Design of Physicians Health Study Il-a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann. Epidemiol. 10 125-34... 

In general, those individuals with baseline hsCRP values in the top quartile of the sample distribution are 2 to 3 times more likely to experience a future vascular event than those in the bottom quartile. The association between hsCRP and future vascular events is linear and is independent of age, smoking, hypertension, dysHpidemia, and diabetes. For example, 8-year follow-up data from the Physicians Health Study and the WHS showed that after adjustment for traditional risk factors, there was an increase in a future cardiovascular risk of 26% for men and 33% in women for each quintile increase in baseline hsCRP. ... 

While these are extreme examples of societal attitudes, it is true that women have been excluded from many large, well-published studies, such as the Physicians Health Study of aspirin in cardiovascular disease (Henrekens, 1989). It is also true that many early studies of drugs in phases I and II were conducted in healthy white males 18-40 years old, and the results then extrapolated to women in phase III studies, primarily aimed at expanded efficacy and safety. Only recently, Paul Williams (1996) confirmed that exercise... 

Albert, C.M., Gaziano, M., Willett, W.C., and Manson, J.E. 2002. Nut consumption and decreased risk of sudden cardiac death in the Physicians Health Study. Arch. Intern. Med. 162, 1382-1387. 

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