report of the conference on low blood cholesterol mortality associations background a national heart lung and blood institute nhlbi conference was held october 910 1990 to review and discuss existing data on ushaped relations found between mortality rates and blood total cholesterol levels tc in some but not other studies presentations were given from 19 cohort studies from the united states europe israel and japan a representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry tc levels in regard to death and these were incorporated into a formal statistical overview adjusted for age diastolic blood pressure cigarette smoking body mass index and alcohol intake as availablemethods and results the ushape for total mortality in men and the flat relation in women resulted largely from a positive relation of tc with coronary heart disease death and an inverse relation with deaths caused by some cancers eg lung but not colon respiratory disease digestive disease trauma and residual deaths risk for combined noncardiovascular noncancer causes of death decreased steadily across the range of tc the conference considered possible explanations for the statistical associations found between low tc levels or active tc lowering and certain causes of death one is that tc is lowered by some disease conditions themselves such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterolbearing lipoproteins with liver disease in this sort of situation the tcmortality association found in observational studies may be due to preexisting disease this was addressed by excluding early deaths from the analysis which did not change the results the conference considered as well the biological function of cholesterol which if seriously deranged might hypothetically cause a wide variety of diseases and dysfunction the conference also considered the biological functions that might provide plausible mechanisms for the associations foundconclusions definitive interpretation of the associations observed was not possible although most participants considered it likely that many of the statistical associations of low or lowered tc level are explainable by confounding in one form or another the conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy further research is recommended to explain the observed associations of low tc levels and tc lowering with certain noncardiovascular diseases this includes studies of the time course of tc change in disease the relation of tc to morbidity further studies of possible epidemiological confounding monitoring of population trends in tc and mortality further studies of the relations in women auditing of noncardiovascular events in trials studies of cell membrane genetic and molecular links to cholesterol metabolism tc level and disease studies of disease manifestations in specific lipid disorders and further study of the proposed causal mechanisms linking low tc and hemorrhagic stroke