University of Minnesota

Contributions of CVD Epidemiology (part 2): Laboratory and Clinical Science

New fields of inquiry on basic mechanisms in CVD have opened, as have new clinical investigations, with clues from epidemiological observations, enriching the interactions among the three major research strategies of medicine. Consider a few examples:

  • Epidemiological findings on the relation of diet, blood lipids, and the atherosclerotic diseases have led to an immense and active field of bench and clinical investigation on the role of lipoproteins.
  • The specific association of HDL with reduced risk of coronary events has led to an explosion of interest in the role of HDL in evolution of the plaque and in genetic control of the apolipoproteins.
  • The risk associations of LP (a) and of LP particle size have led to new molecular and genetic studies on vascular and thrombogenic effects.
  • The epidemiologically established risk associated with “metabolic syndrome” has spawned much metabolic study of insulin sensitivity, tissue resistance, and sodium handling in the pathogenesis of obesity, hypertension, and atherosclerosis.
  • Epidemiologic findings on the interrelations of dietary sodium, potassium, calcium, and magnesium with arterial pressure have stimulated clinical and laboratory studies of neurohormonal and dietary roles in hypertension.
  • Findings on the association of female hormones, tobacco, and CVD risk in women have led to basic new studies of hemostatic mechanisms.
  • Findings on trends in risk factor levels, migration effects, and CVD rates have accentuated clinical interest in causes, treatment, and prevention of CVD.
  • The inverse association of marine and vegetable oils with thrombosis and atherosclerosis opened a major area of basic studies on omega-3 fatty acids, the arachidonic acid-prostacyclin cycle and platelet activity, and on chemopreventive strategies.
  • The inverse association of vegetable, fruit, and whole grain intake and CVD risk has complemented and stimulated basic studies of peroxidation, lipoproteins, and atherosclerosis.
  • The inverse association of fruit, grain, and vegetable diets and risk of many cancers has led to much laboratory research and to trials of chemopreventive agents.
  • The “natural experiment” of Japan, and the Japanese resistance to CVD and many cancers, in the face of heavy smoking, hypertension, and Westernized eating patterns, has stimulated studies of the “protective” roles of nutrients, antioxidants, and omega-3 fatty acids.
  • The “natural experiment” of Finland and its propensity to atherosclerosis has stimulated study of anti-oxidants, selenium, and of other elements deficient or excessive in Finnish diets.
  • Findings of a U-shaped distribution of the risk of CVD according to alcohol consumption has led to extensive study of possible preventive mechanisms in hemostasis and lipoprotein metabolism.
  • Epidemiologic findings of the frequency of type I diabetes has led to studies of twin concordance of human leukocyte antigen associations and of the viral initiation of juvenile diabetes.
  • Epidemiologic findings of excess adult chronic disease and CVD risk associated with low birth weight and excess weight gain in childhood has evoked a major new field of environmental influences on in-utero development.
  • Interactions of dietary antioxidants and tobacco smoking in association with epithelial malignancies has created a new thrust in studies of cancerogenesis and prevention.
  • Associations of dietary intake of fats, fruits, vegetables, legumes, and calcium with colon cancer have stimulated bench and clinical investigations on bile acid metabolism, bowel transit time, fecal bulk, and colonic epitehlial proliferation.
  • Epidemiologic associations of obesity, parity, hormone therapy, and family history with risk of breast cancer has opened areas of research on estrogen and estrogen receptors and hormonal stimuli of carcinogenesis, and on antiestrogen effects.
  • Burkitt’s observations on the inverse ecologic association of diet fiber intake and colon cancer in Africa, have led to the extensive study of diet fiber, physiologic effects, and health.
  • Findings on interactions of tobacco and asbestos, dyes, and irradiation exposure, and of tobacco and alcohol consumption, have led to new ideas about, and the identification of, new co-carcinogens.
  • Epidemiologic distribution of cancers led to discovery of the Epstein-Barr virus, of the role of human papilloma and herpes viruses, of viral DNA in cervical epithelium, and of other aspects of viral carcinogenesis.
  • The clinical-epidemiologic linkage of retinoblastoma and the R6 gene has led to broader models of carcinogenesis and tumor-suppressor genes.
  • The clinical-epidemiological linkage of Kaposi tumors and pneumocystic pneumonia in homosexual men led to the rapid proliferation of studies leading to discovery of the human immunodefiency virus and to therapy and vaccines for the acquired immune deficiency syndrome.
  • and others! (Henry Blackburn)