[ Editorials | Departments and Series | Index ]

Cardiovascular Series

Update on Hypertension in Women

Jimmy H. Hara, MD

Hypertension is the most common chronic disease in the United States, affecting 29% of the adult population.¹ It represents the leading reason for adult physician office visits, accounting for more than 1 million physician appointments per year. Hypertension is a major risk factor for stroke, myocardial infarction (MI), congestive heart failure, and chronic renal disease.² Despite extensive efforts at professional and public education regarding the risks of hypertension and benefits of treatment, fewer than 60% of hypertensive adults are receiving treatment, and only about 50% of those who are treated achieve control of their disease.³

EPIDEMIOLOGY

Current data estimate that more than 58 million US adults either have hypertension or are taking antihypertensive medications, and an additional 45 million have prehypertension.^1,3 Whereas diastolic blood pressure (BP) tends to "plateau" in the fifth decade and may even decline thereafter, systolic BP continues to rise through the seventh decade. Thus, while diastolic BP is a major predictor of cardiovascular morbidity and mortality in those younger than age 50 years, systolic BP is a major predictor in those over age 60 years.⁴ Although hypertension is more common in men than in women among middle-aged individuals, it becomes more common in women after age 60 years. The prevalence of hypertension increases with age, also shifting the preponderance toward women. For a normotensive person in the United States, the lifetime risk of developing hypertension approaches 90%.⁵ According to the US Census of 2000, women accounted for 70% of the population over age 85 years.⁶ Therefore, isolated systolic hypertension is a major health problem among older women.

back to top

DEFINITIONS

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure published its seventh report (JNC-7) in 2003.3 It redefined hypertension into stages 1 and 2, eliminating the stage 3 hypertension described in the previous report.³ Table 1 lists the new classification of BP for adults aged 18 years and older. According to JNC-7, normal BP is defined as a systolic value of < 120 mm Hg and a diastolic value of < 80 mm Hg. Based on a meta-analysis of studies relating BP level to cardiovascular morbidity and mortality, a value of < 115/75 mm Hg is now defined as optimal.⁷

Because individuals with BP above the newly defined normal value of 120/80 mm Hg are at increased risk for the development of target-organ damage and progression to frank hypertension over time, values ranging from 120 to 139 mm Hg systolic and 80 to 89 mm Hg diastolic are now defined as prehypertensive.³ For individuals with diabetes or renal disease, values in the prehypertensive range impose a significantly higher risk than in otherwise healthy individuals; therefore, a lower threshold is indicated for therapeutic intervention in these patients—ie, 130 mm Hg systolic and 80 mm Hg diastolic, rather than 140 mm Hg systolic and 90 mm Hg diastolic.

Table is not available.

TABLE 1. Blood Pressure Classification3*

back to top

PATHOPHYSIOLOGY AND GENETIC FACTORS

Blood pressure is the product of peripheral vascular resistance and cardiac output. Peripheral vascular resistance is determined by vascular tone, whereas cardiac output is determined by extracellular fluid volume and the contractile state of the heart. A central hypothesis for the pathogenesis of hypertension involves the interaction between the sympathetic nervous system (which influences vascular tone and cardiac contractility), dietary sodium intake, and defects in renal sodium excretion (which controls extracellular fluid volume).⁸ Guyton⁸ hypothesized that hypertension develops when the kidneys require a higher BP to maintain extracellular volume within normal limits. Thus, with impaired renal sodium excretion, a higher BP would be required to maintain normal extracellular volume. Studies support the possibility of an inherited defect in renal sodium excretion as the basis of human essential hypertension.⁹ Most monogenetic forms of hypertension discovered to date involve mutations that impair renal sodium excretion by either increasing mineralocorticoid activity or influencing tubular sodium transport systems.⁹

Other lines of evidence suggest that increased sympathetic nervous system activity has an important role in causing hypertension in some persons.¹⁰ These cases could be the result of a genetic tendency toward increased sympathetic activity interacting with repetitive psychogenic stress, obesity, or high sodium intake. Weight gain and obesity are associated with an increased risk of hypertension. A number of humoral factors may be responsible, including increased sympathetic nervous activity, possibly via stimulation of the sympathetic nervous system by leptin.^11,12

back to top

DIAGNOSIS

Diagnosis is based on multiple office measurements of BP performed in a rigorous fashion using a well-maintained aneroid or mercury sphygmomanometer with an appropriate-sized BP cuff (Table 2). Studies show that these guidelines for proper BP measurement are rarely followed in most clinics and offices.¹³ Diagnosis requires findings of elevated average BP (taken at least twice) on at least two separate office visits.^3,13

Various studies indicate that determinations from ambulatory monitoring correlate better with actual BP than do office measurements.¹⁴ Ambulatory BP monitoring is the best method for establishing the presence of isolated "clinic" hypertension (ie, "white-coat" hypertension), which in turn is the most common form of isolated systolic hypertension.³ Self-checks are also useful in selected patients and may improve adherence to therapy; these are also useful for evaluating white-coat hypertension.³

Table is not available.

TABLE 2. Proper Blood Pressure Measurement Technique

Initial Evaluation

There are four major objectives in the initial evaluation of a patient found to have elevated BP: to discover lifestyle factors contributing to the diagnosis and conferring increased cardiovascular risk; to identify associated modifiable risk factors with a potential for therapeutic lifestyle change; to assess for target-organ damage and clinical cardiovascular disease (CCD); and to detect secondary causes of hypertension.^3,15 The second and third objectives are important for risk stratification, which defines the BP thresholds for initiating therapeutic lifestyle changes and drug therapy.^3,15

Secondary hypertension accounts for 5% to 10% of most primary care practices. Secondary causes should be sought in patients with an age of onset younger than 30 years or older than 60 years, significant target-organ damage at the time of diagnosis, refractory hypertension, or hypertensive emergencies/urgencies.¹⁶ Important causes of secondary hypertension include pheochromocytoma, renovascular hypertension, Cushing syndrome, coarctation of the aorta, and polycystic kidney disease.¹⁶

History and Physical Examination

Historical features of importance include family history of premature cardiovascular disease (CVD), renal disease, or endocrinopathy; evidence of target-organ damage or CCD; obesity; excessive alcohol or caffeine consumption; tobacco use; or cocaine addiction.³ A thorough medication review—including over-the-counter and herbal products—is important. In women, the physician should inquire into use of hormonal contraceptives, menopausal hormone therapy, and ephedra, ma huang, or aristolochic acid as dietary supplements. In patients with a history of hypertension, the prior BP readings, treatments, and efficacy of therapy should be ascertained.^3,15

The examination should include at least two standardized BP readings.¹³ Height and weight should be measured to calculate body mass index (BMI) and, if possible, waist circumference should also be measured.^10-12 Retinal examination can identify changes suggesting target-organ damage due to hypertension and/or diabetes (eg, hemorrhage, exudate, papilledema). Common findings such as arteriolar narrowing, arteriovenous crossing changes (eg, "AV nicking"), and focal constrictions are actually more closely associated with atherosclerosis, which may be accelerated as a result of hypertension.¹⁷ A careful cardiovascular examination should focus on determination of left ventricular hypertrophy, evidence of congestive cardiac decompensation, and the presence of arterial bruits.

Laboratory Investigation

Laboratory investigation can provide information about cardiac risk, target-organ damage, evidence of secondary hypertension, and baseline data in anticipation of subsequent drug therapy.³ Serum lipid, potassium, creatinine, and glucose testing, electrocardiography, urinalysis, and calculation of glomerular filtration rate (GFR) by either the Modification of Diet in Renal Disease method or the Cockroft-Gault equation are recommended by JNC-7.^3,18 Chest radiography and measurement of hemoglobin, hematocrit, uric acid, and calcium values are also recommended, depending on the clinical circumstances.^3,16 Additional studies are not generally advised unless the history, physical findings, or initial laboratory studies are inconsistent with essential hypertension or suggest a specific secondary etiology.¹⁶

back to top

RISK STRATIFICATION

Specific factors in the individual patient are used to determine the BP threshold, timing of drug therapy, and treatment goals.³ Table 3 outlines risk stratification and treatment of hypertensive patients based on BP level, hypertensive risk factors, presence or absence of diabetes or chronic renal disease, and presence or absence of CCD. Hypertensive risk factors include:

• Cigarette smoking
• Dyslipidemia
• Diabetes
• Aged 65 years or older (for women)
• Postmenopausal status
• Family history of premature CVD (before age 55 years in female relatives or before age 45 years in male relatives)
• Nephropathy (microalbuminuria with a creatinine level exceeding 30 mcg/mg, or a GFR of < 60 mL/min)
• Obesity (BMI of more than 30 kg/m² or waist circumference exceeding 88 cm in women)
• C-reactive protein level exceeding 1 mg/dL
• Physical inactivity/sedentary lifestyle.^3,15

back to top

TREATMENT

Therapeutic Lifestyle Change

The term "therapeutic lifestyle change" is now preferred over the older term "lifestyle modification," as the former implies modification in a healthier direction. Therapeutic lifestyle change should be encouraged for all levels of hypertension risk and elevated BP. Therapeutic lifestyle change alone may be tried for up to 1 year with stage 1 hypertension in risk group A (no hypertensive risk factors, target-organ damage, or CCD).^3,15 For stage 1 hypertension in risk group B (hypertension risk factors but no diabetes, target-organ damage, or CCD), therapeutic lifestyle change may be tried for 6 months before resorting to medication.^3,15 Medication use is indicated for patients with diabetes and evidence of target-organ damage or CCD (risk group C) and any level of BP elevation (prehypertension, stage 1 and 2 hypertension).^3,15 For stage 2 hypertension, both therapeutic lifestyle change and medication use are recommended.

Various goals for therapeutic lifestyle change are identified by JNC-7.3 Weight reduction is recommended for those with a BMI of over 25 kg/m², with an expected 5- to 20-mm-Hg diastolic BP reduction for every 10 kg of weight lost.^3,11,12 Patients should be advised to follow the Dietary Approaches to Stop Hypertension diet,^3,19 which is rich in fruits, vegetables, and low-fat dairy products with reduced saturated and total-fat content.^3,19 Salt intake should be reduced to 6 g/d (2.4 g/d of sodium). Alcohol consumption should be limited to one drink/day for women, with one drink equaling 0.5 oz or 15 mL of ethanol (eg, 12 oz of beer, 5 oz of wine, 1.5 oz of whiskey).^3,19 Regular aerobic exercise (eg, brisk walking for at least 30 min/d on most days of the week) is advised. Cigarette smoking should be strongly discouraged, and physicians should actively help patients explore strategies for quitting.

Pharmacologic Treatment

Four major classes of antihypertensive medications are recommended for first-line therapy: thiazide diuretics, β-adrenergic blockers, calcium channel blockers (CCBs), and angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). In special circumstances, other adrenergic agents (eg, α-adrenergic blockers) may be employed. The initial drugs of choice are the thiazide diuretics.,^3,20

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial²⁰ was designed to determine whether treatment with a diuretic was in fact superior to treatment with an α-adrenergic blocker, calcium antagonist, or ACE inhibitor for both lowering BP and preventing cardiac events in high-risk adults with hypertension. The α-adrenergic-blocker arm was discontinued because of an almost 2-fold increase in the risk of heart failure. Based on these findings, α-adrenergic blockers are no longer considered first-line agents for treating hypertension. Compared with the diuretic group, the ACE-inhibitor group had an increased risk of stroke, particularly among black patients. Therefore, in black patients, thiazide diuretics should be used first. Finally, unless diabetes is present with microalbuminuria or congestive heart failure, other agents might be preferred over ACE inhibitors.²⁰

The Second Australian National Blood Pressure Study studied more than 6,000 patients aged 65 to 84 years, concluding that in the elderly, initiation of treatment with ACE inhibitors appeared to lead to better outcomes than did thiazide diuretics.²¹ Clinical guidelines for the treatment of hypertension in diabetic patients give priority to controlling BP, recommending a treatment goal of 135/80 mm Hg using thiazide diuretics, ACE inhibitors, and ARBs as first-line therapy.²² In diabetic patients, β-adrenergic blockers, and CCBs are considered second-choice agents.²²

The JNC-7 also outlines compelling indications for the choice of specific antihypertensive medications in specific clinical circumstances (Table 4). Thiazide diuretics are indicated for most indications—except for chronic kidney disease, where thiazides are usually contraindicated due to elevated creatinine levels.²⁰

Table is not available.

TABLE 4. Compelling Indications for Specific Antihypertensive Drug Classes3

Pharmacologic treatment should generally begin using monotherapy with a thiazide diuretic for stage 1 hypertension, and two drugs for stage 2 hypertension.³ The goal of treatment is a BP of 140/90 mm Hg. In patients with chronic kidney disease, the goal of treatment is 130/80 mm Hg. The JNC-7 sets a treatment goal for patients with diabetes mellitus at 130/80 mm Hg, which differs from the American College of Physicians guideline goal of 135/80 mm Hg.^3,22

Pregnancy

Blood pressure levels exceeding 140/90 mm Hg complicate 6% to 8% of pregnancies, ranking only behind embolism as a cause of maternal death.^23,24 Hypertension in pregnancy can be related to chronic hypertension (present prior to 20 weeks' gestation), preeclampsia/eclampsia, preeclampsia /eclampsia superimposed on chronic hypertension, or gestational hypertension (onset after 20 weeks' gestation).^23,24 In chronic hypertension, thiazide diuretics may be continued, particularly in patients with stage 2 hypertension.²⁴ For gestational hypertension, however, thiazide diuretics should not be initiated²³; hydralazine and methyldopa both have favorable safety profiles and are the drugs of choice. Atenolol can cause intrauterine growth retardation if used in the first trimester, but labetalol and metoprolol are acceptable alternatives.²⁵ The ACE inhibitors and ARBs are contraindicated in pregnancy.^3,23,24

back to top

COMPLICATIONS

Left untreated, hypertension leads to serious disability and death.² Hypertension is the single most important cause of stroke, which in turn is the third leading cause of death in the United States.²⁶ Hypertension in midlife is associated with an increased risk of cognitive dysfunction and dementia in later years; this is felt to be due primarily to multiple strokes with resultant vascular dementia, but may even occur in the absence of clinically apparent strokes.^26,27 Hypertension is the second leading cause of end-stage renal disease, especially in blacks.²⁸ It can also cause loss of vision through a variety of mechanisms, including retinal artery/vein occlusions, ischemic optic neuropathy, venostatic retinopathy, and macular edema.²⁹

back to top

CONCLUSION

Effective treatment has a dramatic effect on the prognosis of patients with hypertension. Multiple prospective treatment trials over the past three decades have established that BP reduction can markedly reduce cardiovascular morbidity and mortality. However, even when BP is reduced to currently recommended levels, hypertensive individuals remain at higher risk for cardiovascular events compared with normotensive individuals, particularly those with target-organ damage. Thus, these observations argue for the widespread application of public health strategies and individual therapies as recommended by JNC-7.

back to top

Jimmy H. Hara, MD, is family medicine residency director, Kaiser Permanente, Los Angeles, Calif; and associate clinical professor of family medicine, David Geffen School of Medicine at University of California-Los Angeles.

References

1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003;290(2):199-206.
2. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA. 1996;275(20):1571-1576.
3. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA. 2003;289(19):2560-2572.
4. Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation. 2001; 103(9):1245-1249.
5. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Study. JAMA. 2002;287(8):1003-1010.
6. The Older Population in the United States: March 2002. United States Bureau of Census Web site. Available at: http://www.census.gov/prod/2003pubs/p20-546.pdf. Accessed February 14, 2005.
7. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data from one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-1913.
8. Guyton AC. Kidneys and fluids in pressure regulation. Small volume but large pressure changes. Hypertension. 1992;19(1 Suppl):I2-I8.
9. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104(4):545-556.
10. Esler M, Rumantir M, Kaye D, Lambert G. The sympathetic neurobiology of essential hypertension: disparate influences of obesity, stress, and noradrenaline transporter dysfunction? Am J Hypertens. 2001;14(6 Pt 2):139S-146S.
11. Grassi G, Seravalle G, Dell'Oro R, Turri C, Bolla GB, Mancia G. Adrenergic and reflex abnormalities in obesity-related hypertension. Hypertension. 2000;36(4):538-542.
12. Haynes WG, Morgan DA, Walsh SA, Sivitz WI, Mark AL. Cardiovascular consequences of obesity: role of leptin. Clin Exp Phamacol Physiol. 1998;25(1):65-69.
13. Recommendations for routine blood pressure measurement by indirect cuff sphygmomanometry. American Society of Hypertension. Am J Hypertens. 1992;5(4 Pt 1):207-209.
14. Clement DL, De Buyzere ML, De Bacquer DA, et al. Prognostic value of ambulatory blood pressure recordings in patients with treated hypertension. N Engl J Med. 2003;348(24): 2407-2415.
15. European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003; 21(6):1011-1053.
16. Kaplan NM. Other secondary forms of hypertension. In: Kaplan NM, Lieberman, E, Neal W, eds. Kaplan's Clinical Hypertension, 8th ed. Lippincott Williams & Wilkins, Philadelphia, Pa. 2002: 495.
17. Fuchs FD, Maestri MK, Bredemeier M, et al. Study of the usefulness of optic fundi examination of patients with hypertension in a clinical setting. J Hum Hypertens. 1995;9(7): 547-551.
18. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Int Med. 1999;130(6):461-470.
19. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001; 344(1):3-10.
20. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-2997.
21. Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348(7): 583-592.
22. Vijan S, Hayward RA. Treatment of hypertension in type 2 diabetes mellitus: blood pressure goals, choice of agents, and setting priorities in diabetes care. Ann Intern Med. 2003;138(7):593-602.
23. ACOG Technical Bulletin. Hypertension in pregnancy. No. 219, January 1996 (replaces No. 91, February 1986). Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1996;53(2):175-183.
24. Sibai BM. Chronic hypertension in pregnancy. Obstet Gynecol. 2002;100(2):369-377.
25. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. Br Med J. 1990;301(6752):587-589.
26. Arias E, Smith BL. Deaths: Preliminary Data for 2001. National Vital Statistics Reports, Vol. 51, No. 5. Hyattsville, Md: National Center for Health Statistics; 2003.
27. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function: the Honolulu-Asia Aging Study. JAMA. 1995;274(23):1846-1851.
28. Fatica RA, Port FK, Young EW. Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States. Am J Kidney Dis. 2001;37(6):1184-1190.
29. Locke LC. Ocular manifestations of hypertension. Optom Clin. 1992;2(2):47-76.

back to top