A prospective study in primary care in patients without vascular disease comparing levels of coronary risk factors in those recommended for lipid-lowering drugs based on either absolute risk or absolute risk reduction.

In the United Kingdom, the current recommendation is that lipid-lowering drugs should be prescribed for primary prevention only to subjects with an absolute coronary risk (AR) greater than 15% in 5 years (i.e., myocardial infarction or angina). However, to achieve greater benefit it may be preferable to direct treatment to those patients showing the greatest absolute risk reduction (ARR). The aim of this study was to compare the characteristics of subjects eligible for lipid-lowering drugs based on the AR criteria or on an ARR of >4.45%. A prospective study was carried out over 29 months in primary care in a part of the United Kingdom with a prevalence of coronary disease nearly 20% above the national average. Risk factors were recorded in men and women aged 30-75 years who were being considered by their primary care physician for lipid-lowering drug therapy. Of the 2351 patients included in the study, 2139 (91%) and 101 (4.3%) were, respectively, below and above the criteria for treatment by both AR and ARR criteria. In 111 (4.7%) subjects, treatment was recommended based on only one of the criteria-82 on AR and 29 on ARR. Comparing these two groups, those treated on AR only were older (mean age 68.1 years [SD, 4.1] vs. 49.1 years [SD, 4.6]; p<0.0001) and had a lower total cholesterol (260 vs. 288 mg/dL; p=0.015); higher high-density lipoprotein cholesterol (50 vs. 43 mg/dL; p=0.003), lower low-density lipoprotein cholesterol (160 vs. 184 mg/dL; p=0.03), a lower total to high-density lipoprotein cholesterol ratio (5.4 vs. 7.1; p<0.0001), and lower triglycerides (258 vs. 435 mg/dL; p=0.007). The AR group also had a higher mean systolic blood pressure (170.9 vs. 158.9 mm Hg; p=0.013), presumably an attribute of their greater age. Although the AR and ARR groups did not show a difference in the proportion of males or diabetics, there was a significantly greater proportion of smokers in the latter group (72% vs. 35%; p=0.001). In conclusion, treatment recommendations based on AR alone would result in nontreatment of young subjects with significant hyperlipidemia and at high relative risk of coronary disease, whereas lipid-lowering drugs would be given preferentially to patients whose main coronary heart disease risk factors are age and hypertension but not hyperlipidemia. By contrast, treatment recommendations based on ARR ensure that lipid-lowering drugs are directed to patients who will derive the most benefit. Furthermore, delaying treatment in younger subjects at high relative risk but not high AR results in their accumulating significant coronary risk in the years before their AR exceeds an arbitrary threshold before lipid-lowering drugs are prescribed.

Low dose, early mucosal exposure will minimize the risk of microbial disease.

In the 21st century we will rediscover the germ theory of disease: germs not only cause infection as described in standard textbooks but also have a pathogenic role in autoimmunity, atherosclerosis, cancer and even acute psychiatric conditions. In order to reduce morbidity and mortality caused by common organisms we should ensure that exposure is early, often, by the mucosal route and in low dose. Micro-organisms should be delivered daily throughout life by respiratory mucosal spray or enteric coated pill, in precise dose and in a predetermined schedule.