ATHEROSCLEROSIS UPDATE ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society / Societe canadienne d'atherosclerose
The nature of essential hypertension John S. Floras, MD, DPhil, FRCPC
In 1988 Reaven' postulated an association between essential hypertension, glucose intolerance, hyperinsulinemia and dyslipidemia and proposed that insulin resistance is common and causal to these abnormalities. This idea has stimulated considerable experimental and clinical activity. That this hypothesis assumes a qualitative fault and therefore represents a challenge to our current concept of primary hypertension as a quantitative disorder has, in contrast, received little attention. Primary hypertension emerged from the debates (1947 to 1964) between Sir George Pickering and Baron Robert Platt as a quantitative disorder of cardiovascular regulation.2 Many mechanisms were involved in blood pressure regulation. Genetic and environmental factors that acted on those mechanisms to raise the blood pressure operated on the population as a whole, were different in degree rather than in kind in those with essential hypertension and could not be explained by a single specific qualitative fault or genetic defect (page 108). On the basis of the available evidence Pickering and colleagues concluded that "any attempt to divide pressure sharply into normal and abnormal is artificial" (page 42). However, Pickering was quick to emphasize that his novel concept of a quantitative disease was open to refutation: "While [no specific fault responsible for hypertension] has as yet been discovered, were such a discovery to be made, the whole problem would be transformed" (page 82). Has this occurred? In his review Reaven' characterized hypertension as a state of insulin resistance and held this specific fault responsible for hyperglycemia, hyperinsulinemia, increased plasma levels of very-low-density lipoprotein triglyceride and decreased plasma levels of high-density lipoprotein cholesterol, thereby linking in the same individual a number of important risk factors for coronary artery
disease. Similar metabolic abnormalities precede the development of high blood pressure in spontaneously hypertensive rats3 and have been observed in normotensive offspring of hypertensive parents.4 Other authors have been more cautious, proposing instead a model of polygenic abnormalities underlying a network of physiologically interrelated functions perhaps linked by insulin.5 Indeed, the strongest genetic evidence to date links spontaneous hypertension in rats to the gene encoding for angiotensin converting enzyme.6 Although it may be premature to redefine essential hypertension as a qualitative disorder of cardiovascular regulation, identification of the specific faults with greatest adverse implications for coronary and cerebrovascular disease may well become the major criterion for establishing the diagnosis of or the need to treat hypertension, with documentation of blood pressure readings in excess of an arbitrary level a minor, quantitative adjunct to this process. If so, much of the current debate on the quantitative component of this disorder (e.g., which level of blood pressure to treat) may become irrelevant.
References 1. Reaven GM: Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607 2. Swales JD (ed): Platt versus Pickering: an Episode in Recent Medical History, Keynes Pr, Cambridge, 1985 3. Reaven GM, Chang H: Relationship between blood pressure, plasma insulin and triglyceride concentration, and insulin action in SHR and WKY rats. Am J Hypertens 1991; 4: 34-38 4. Ferrari P, Weidmann P, Shaw S et al: Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent. Am JMed 1991; 91: 589-596 5. Ferrannini E: Metabolic abnormalities of hypertension: a lesson in complexity. Hypertension 1991; 18: 636-639 6. Lindpaintner K: Genetic linkage analysis in hypertension: principles and practice. J Hypertens 1992; 10: 121-124
This article was made possible by an educational grant to the Canadian Atherosclerosis Society (CAS) from Merck Frosst Canada Inc., but the author and the content ofthe article were determined solely by the CAS. Dr. Floras is the recipient of a Career Scientist Award from the Ontario Ministry of Health. The opinions expressed herein are his and not necessarily those of the CAS or the ministry.
Reprint requests to: Dr. John S. Floras, 12 EN-234, Division of Cardiology, Toronto General Hospital, 200 Elizabeth St., Toronto, ON M5G 2C4 -
For prascribing information see page 1604
CAN MED ASSOC J 1992; 147 (10)
1509
The nature of essential hypertension John S. Floras, MD, DPhil, FRCPC
In 1988 Reaven' postulated an association between essential hypertension, glucose intolerance, hyperinsulinemia and dyslipidemia and proposed that insulin resistance is common and causal to these abnormalities. This idea has stimulated considerable experimental and clinical activity. That this hypothesis assumes a qualitative fault and therefore represents a challenge to our current concept of primary hypertension as a quantitative disorder has, in contrast, received little attention. Primary hypertension emerged from the debates (1947 to 1964) between Sir George Pickering and Baron Robert Platt as a quantitative disorder of cardiovascular regulation.2 Many mechanisms were involved in blood pressure regulation. Genetic and environmental factors that acted on those mechanisms to raise the blood pressure operated on the population as a whole, were different in degree rather than in kind in those with essential hypertension and could not be explained by a single specific qualitative fault or genetic defect (page 108). On the basis of the available evidence Pickering and colleagues concluded that "any attempt to divide pressure sharply into normal and abnormal is artificial" (page 42). However, Pickering was quick to emphasize that his novel concept of a quantitative disease was open to refutation: "While [no specific fault responsible for hypertension] has as yet been discovered, were such a discovery to be made, the whole problem would be transformed" (page 82). Has this occurred? In his review Reaven' characterized hypertension as a state of insulin resistance and held this specific fault responsible for hyperglycemia, hyperinsulinemia, increased plasma levels of very-low-density lipoprotein triglyceride and decreased plasma levels of high-density lipoprotein cholesterol, thereby linking in the same individual a number of important risk factors for coronary artery
disease. Similar metabolic abnormalities precede the development of high blood pressure in spontaneously hypertensive rats3 and have been observed in normotensive offspring of hypertensive parents.4 Other authors have been more cautious, proposing instead a model of polygenic abnormalities underlying a network of physiologically interrelated functions perhaps linked by insulin.5 Indeed, the strongest genetic evidence to date links spontaneous hypertension in rats to the gene encoding for angiotensin converting enzyme.6 Although it may be premature to redefine essential hypertension as a qualitative disorder of cardiovascular regulation, identification of the specific faults with greatest adverse implications for coronary and cerebrovascular disease may well become the major criterion for establishing the diagnosis of or the need to treat hypertension, with documentation of blood pressure readings in excess of an arbitrary level a minor, quantitative adjunct to this process. If so, much of the current debate on the quantitative component of this disorder (e.g., which level of blood pressure to treat) may become irrelevant.
References 1. Reaven GM: Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607 2. Swales JD (ed): Platt versus Pickering: an Episode in Recent Medical History, Keynes Pr, Cambridge, 1985 3. Reaven GM, Chang H: Relationship between blood pressure, plasma insulin and triglyceride concentration, and insulin action in SHR and WKY rats. Am J Hypertens 1991; 4: 34-38 4. Ferrari P, Weidmann P, Shaw S et al: Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent. Am JMed 1991; 91: 589-596 5. Ferrannini E: Metabolic abnormalities of hypertension: a lesson in complexity. Hypertension 1991; 18: 636-639 6. Lindpaintner K: Genetic linkage analysis in hypertension: principles and practice. J Hypertens 1992; 10: 121-124
This article was made possible by an educational grant to the Canadian Atherosclerosis Society (CAS) from Merck Frosst Canada Inc., but the author and the content ofthe article were determined solely by the CAS. Dr. Floras is the recipient of a Career Scientist Award from the Ontario Ministry of Health. The opinions expressed herein are his and not necessarily those of the CAS or the ministry.
Reprint requests to: Dr. John S. Floras, 12 EN-234, Division of Cardiology, Toronto General Hospital, 200 Elizabeth St., Toronto, ON M5G 2C4 -
For prascribing information see page 1604
CAN MED ASSOC J 1992; 147 (10)
1509
