These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men. Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.

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BACKGROUNDPrevious trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODSIn one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTSThe overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P = 0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P = 0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P = 0.005). CONCLUSIONSTreatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.)

Exercise cardiac output has been measured by an indirect Fick technique in 94 normal subjects (48 men and 46 women) whose ages ranged from 20 to 85 years. With increasing age, exercise cardiac output was found to be greater despite no such trend in oxygen uptake; in consequence, exercise arteriovenous oxygen difference decreased with age. These trends were seen in both sexes, though the age effects were apparent a decade earlier in men. In addition, in men the heart rate was lower and stroke volume higher with increasing age. By contrast, no age effect on exercise pulse rate was noted in women. When the sexes were compared, exercise cardiac output was higher in women of the younger two decades (20 to 39 years), a difference which was not apparent in subsequent decades. sex differences in exercise cardiac output; age differences in exercise cardiac output; stroke volume during exercise; oxygen pulse during exercise Submitted on January 13, 1965