Hypertension

September 14, 2011

Hypertension (high blood pressure) is defined as a blood pressure of 140/90 mm Hg or higher when measured with a blood pressure cuff or being on medication for high blood pressure. The systolic pressure is the upper number of the reading, while the diastolic pressure is the lower number of the reading. Hypertension is a major risk factor for heart disease, which is the leading cause of death for women in the United States. Blood pressure increases with age with the increase in systolic pressure more pronounced in patients greater than 65 years old. Systolic hypertension is an elevated reading in the top number of the reading when measured by a blood pressure cuff. Sixtyfive to seventy-five percent of hypertension in the elderly is isolated systolic hypertension, with the prevalence of isolated systolic hypertension higher in elderly women than men.

In the third National Health and Nutrition Examination Survey (NHANES III), although persons 65 years of age or older represented only 19% of the total population, they constituted 45% of persons with hypertension who were unaware of their condition, 32% of those who were aware of their condition but not being treated, and 57% of those who had treated but still had uncontrolled hypertension.

The prevalence of hypertension varies by sex and ethnicity. Compared with men, women under the age of 55 years have less hypertension, women aged 55-74 years have a similar prevalence of hypertension, and women over 75 years old have more hypertension. Blacks have higher rates of hypertension than whites for both women and men. Despite the equal occurrence of hypertension among women and men aged 55-74 and more hypertension in women more than 75 years old, until recently, little was known about the prevalence, treatment, and control of hypertension among older, postmenopausal women. Baseline data from the Women’s Health Initiative (WHI) better define hypertension and its treatment in postmenopausal women.

In the WHI, the prevalence of hypertension was 37.8%. Older women (aged 70-79) had twice the prevalence rate (53.4%) of women 50-59 years (26.7%). Prevalence was higher in blacks than whites or Hispanics (59.3% vs. 35.5% whites and 33.4% in Hispanics) and in lower socioeconomic groups. The prevalence of hypertension was substantially higher among overweight women (body mass index [BMI]>27.3) than those not overweight (48.0% vs. 29.3%). Nondrinkers had a higher prevalence of hypertension than moderate drinkers (46.2% vs. 31.6%) as did women who were sedentary compared with those who performed moderate exercise (45.3% vs. 31%). Women with one cardiovascular risk factor (family history of myocardial infarction [MI], hypercholesterolemia [elevated blood cholesterol], diabetes, or a history of MI, heart failure, or stroke) had higher rates of hypertension than those without such risk factors. Treatment rates did not differ by age, but black women had the highest treatment rates and Hispanic women the lowest (75.6% vs. 59.4%). Most hypertensive patients were treated with one drug (57.6%). The most commonly used drugs in monotherapy (a single drug is used to treat hypertension) were medications in the classes known as calcium channel blockers (16%) followed by diuretics (“water pills”) and angiotensin-converting enzyme (ACE) inhibitors (14%). Beta-blockers (another type of medication used to treat high blood pressure) were used the least (9%). Of those treated, older nonwhite women were less likely to have their hypertension under control. Treatment patterns in WHI women did not follow accepted medical guidelines of the recent sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for the treatment of uncomplicated hypertension, which recommend diuretics and beta-blockers as preferred initial treatments. The WHI data suggest that these guidelines are not followed in the treatment of postmenopausal women, given that the most common drug class used as monotherapy was calcium channel blockers.

RESPONSE TO TREATMENT

The effectiveness of antihypertensive drug treatment in overall reduction in the risk of stroke and other cardiovascular disease events is well established. Large medical studies, such as the Systolic Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in Europe (SYST-EUR) trials, showed that treatment of isolated systolic hypertension with diuretics with and without beta-blockers (SHEP) and calcium channel blockers with or without ACE inhibitor or diuretic (SYST-EUR) reduced the rate of cardiovascular complications and cerebrovascular events in both women and men 60 years old or older—especially diabetics. It remains unclear whether the effect of antihypertensive treatment in reducing cardiovascular risk is dependent on sex. In the Treatment of Mild Hypertension Study, women and men assigned to treatment with antihypertensive drugs with lifestyle intervention versus lifestyle intervention alone experienced greater and generally similar benefits—a decrease in systolic and diastolic blood pressures and a reduction in cardiovascular events. In a review, the “Effect of Antihypertensive Drug Treatment on Cardiovascular Outcomes in Women and Men: A Meta-Analysis of Individual Patient Data from Randomized, Controlled Trials,” women and men treated with antihypertensive medications had similar cardiovascular risk. Quantification of benefit in risk reduction shows that for women, the benefit is primarily in reducing the risk of stroke, whereas in men treatment prevented as many coronary events as strokes. The fact that statistical significance for coronary events or total mortality was not reached in women may have a simple explanation: The numbers of women participating in the study and their low rate of coronary events may have been too small to allow a proper statistical analysis.

Thus, 55to 74-year-old women have the same rate of hypertension as men the same age and women older than 75 have more hypertension than their male counterparts. Hypertension is an important risk factor for the development of coronary heart disease and stroke in both sexes and there is good evidence that both women and men benefit from treatment of hypertension. There is no evidence that women respond differently to antihypertensive therapy than men, except that diuretics may be particularly useful in women. Some adverse effects of individual antihypertensive drugs may be more troublesome in women. ACE inhibitor-related cough is three times more common in women; swelling related to the use of some types of calcium channel blocking medications is more common in women; and hirsutism (excessive body hair) with the medication minoxidil is often intolerable among women.

HYPERTENSION WITH ORAL CONTRACEPTIVES

Oral contraceptive (OC)-induced hypertension affects about 5% of women using OCs. Age greater than 35 years old and obesity are the only known risk factors for OC-induced hypertension. It is not known whether the effects of OCs on blood pressure depend on the dose and type of estrogens and progestins (both “female hormones”) that are used in the formulation of the OC tablets. The onset of OC-induced hypertension usually occurs within 4 months of beginning an OC, although the actual increases in blood pressure may be related to the duration of treatment. Blood pressure usually returns to normal within 1 year after stopping the pill.

The cause of OC-induced hypertension is not well understood. The renin-angiotensin system (enzyme system in the kidney) is activated, but its role in causing hypertension has not been demonstrated; there does not seem to be a significant difference in changes in the renin-angiotensin system between OC users who remain normotensive (normal blood pressure) and those who develop hypertension. Most women on the pill develop renal vasoconstriction (constriction of blood vessels in the kidney); it has been suggested that those with the greatest propensity to develop renal vasoconstriction retain the most sodium and develop hypertension.

HYPERTENSION WITH PREGNANCY

Hypertension affects 10% of pregnancies in the United States and remains a leading cause of both maternal and fetal morbidity and mortality. Hypertension in pregnancy is defined as a systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg; or systolic blood pressure increase of >30 mm Hg or diastolic blood pressure increase of >15 mm Hg over first trimester of prepregnancy values.

Chronic Hypertension

Chronic hypertension is hypertension that is present before pregnancy or diagnosed before the 20th week of gestation or that persists beyond 6 weeks postpartum. Most women have a benign (uncomplicated) course with an exaggerated decrease in diastolic blood pressure of as much as 20 mm Hg that often leads to normalization of blood pressure in midpregnancy. This drop in diastolic blood pressure may mask the diagnosis of chronic hypertension if prepregnancy values are unknown. The blood pressure usually increases to prepregnancy levels in the third trimester, leading to diagnostic confusion with preeclampsia (pregnancyrelated hypertension). Proteinuria (protein in the urine) is absent in uncomplicated chronic hypertension; when it occurs for the first time in the third trimester, it is the best indicator of superimposed preeclampsia. Antihypertensive treatment should be initiated for a systolic blood pressure >150 mm Hg or a diastolic blood pressure >100 mm Hg unless there is evidence of renal disease or other target organ complications in which case antihypertensive therapy is started even earlier when diastolic blood pressure is 90 mm Hg or higher. Women with chronic hypertension are at increased risk for developing preeclampsia, particularly if the blood pressure does not decline in midgestation or if they have secondary hypertension. Ideally, they should be evaluated before pregnancy for hypertension-associated complications such as left ventricular hypertrophy (heart chamber thickening), hypertensive nephropathy (kidney disease), and retinopathy (eye problems in retina). Medications prescribed before pregnancy can be continued during pregnancy except for medications in the classes of ACE inhibitors and angiotensin II receptor blockers. Women taking these medications who present for prepregnancy counseling should be told to use another agent before conception.

Preeclampsia/Eclampsia

Preeclampsia is an increase in blood pressure occurring after 20 weeks’ gestation and is accompanied by proteinuria (protein in the urine) and/or edema (swelling). Preeclampsia usually occurs in and is considered a disease of the first pregnancy. However, women with a history of preeclampsia have an increased risk during subsequent pregnancies. Other risk factors include extremes of reproductive age, multiple gestations (e.g., twins), family history of preeclampsia, chronic hypertension, diabetes mellitus, connective tissue disease, and renal disease. An important feature of preeclampsia is its unpredictable clinical course—women with mild hypertension and minimal proteinuria can have rapid progression to eclampsia. Eclampsia is the occurrence of seizures in a patient with preeclampsia that cannot be attributed to any other cause. The exact cause of preeclampsia and eclampsia are unknown and consequently, specific preventive and treatment options have not been developed. High-risk patients should be evaluated early in pregnancy by an obstetrician with special expertise in this field. If preeclampsia develops at less than 32 weeks’ gestation consideration should be given to postponing delivery when hypertension is mild and no renal, hepatic, or coagulation abnormalities are evident. Patients should be hospitalized for signs of fetal distress, headache, visual disturbances, and right upper quadrant abdominal pain, which may indicate progression to more severe illness. The threshold for initiation of antihypertensive therapy is the same as for chronic hypertension.

An oral agent (hypertension medication that is taken by mouth) is preferred if delivery is not expected within 48 hr. Outpatient management can be considered for asymptomatic patients with treatment-responsive hypertension in the absence of marked proteinuria (protein level

Gestational or Transient Hypertension

Gestational or transient hypertension is hypertension developing after 20 weeks’ gestation without other signs of preeclampsia. This category encompasses both women with preeclampsia who have not yet developed proteinuria and those with hypertension only. The differentiation between these two groups is possible only retrospectively, that is, postpartum. Transient hypertension (the term previously used for this category) refers to a subgroup of women in whom blood pressure returns to normal by 12 weeks postpartum. The failure of blood pressure to normalize leads to the diagnosis of chronic hypertension. Transient hypertension has a benign course and good prognosis, with a tendency to recur in subsequent pregnancies. The blood pressure usually normalizes shortly after delivery, although the risk of developing hypertension later in life is increased.

Treatment of Hypertension in Pregnancy

The choice of antihypertensive medication in pregnancy is limited by concerns for fetal safety. In addition to proven safety, an ideal antihypertensive agent should gradually reduce blood pressure without compromising uteroplacental blood flow to the fetus. According to the Working Group report of the National High Blood Pressure Education Program (NHBPEP) sponsored by National Institutes of Health, first-line oral and intravenous treatments are the medications methyldopa and hydralazine, respectively. Another group of medications, beta-blockers, have demonstrated effective blood pressure control and a satisfactory safety profile when administered in the third trimester. The main concerns with beta-blocker use stem from evidence of intrauterine growth retardation and low placental weight when the beta-blocker (atenolol) was used in the second trimester. Betablockers can potentially cause additional adverse effects such as fetal bradycardia (slowed fetal heart rate), impaired fetal compensatory response to hypoxemia (reduced blood oxygen), and neonatal hypoglycemia (low blood sugar). Data on the safety and efficacy of calcium channel blockers, especially early in pregnancy, are limited. Calcium channel blockers are potent tocolytics (stop uterine contractions) and can affect the progression of labor. Another concern is the potential for profound hypotension (lowered blood pressure) and circulatory collapse when the medication magnesium sulfate is used concurrently with calcium channel blockers for seizure prevention. Nifedipine (calcium channel blocker) has been studied most extensively and decreases blood pressure and improves renal function without affecting blood flow in the umbilical artery. According to the Working Group report of the NHBPEP, diuretics can be continued during pregnancy if initiated before conception, especially in women with salt-sensitive chronic hypertension. Possible adverse effects include electrolyte abnormalities such as hyponatremia (low sodium), hypokalemia (low potassium), and hyperuricemia (high uric acid). Diuretics should be avoided in women with preeclampsia. Medications in the class of ACE inhibitors are contraindicated in pregnancy. They adversely affect the fetal renal system, causing anuria (lack of urine) and oligohydramnios (low amniotic fluid volume). Complications in newborns after in utero ACE inhibitor exposure during the second and third trimester include fetal limb abnormalities, lung hypoplasia (abnormal lung development), craniofacial deformities (deformities of the skull/face), and renal dysplasia (abnormal development of the kidneys). Medications in the class of angiotensin II receptor blockers cause similar hemodynamic (changes in blood flow and pressure) changes and potentially similar fetal malformations. Fetuses of women who take ACE inhibitors or angiotensin II receptor blockers during the first trimester are not considered at a higher risk for these malformations. Nonpharmacologic treatment consists mainly of bed rest, which not only lowers blood pressure but also promotes diuresis (elimination of fluid through increased urination) and reduces premature labor. Pregnant women with sodium-sensitive chronic hypertension should continue salt restriction during pregnancy. Salt restriction is not recommended for routine treatment of women with preeclampsia, who frequently are volume contracted.

SEE ALSO: Cardiovascular disease, Coronary risk factors, Diabetes, Edema, Oral contraception, Pregnancy, Renal diseases, Stroke

Suggested Reading

  • Clezy, T. M., Foy, B. N., Hodge, R. L., & Lumbers, E, R. (1972). Oral contraceptives and hypertension. An epidemiological survey. British Heart Journal, 34, 1238-1243.
  • Garovic, V. D. (2000). Hypertension in pregnancy: Diagnosis and treatment. Concise Review for Clinicians. Mayo Clinic Proceedings, 75, 1071-1076.
  • Gueyffier, F., Boutitie, F., Boissel, J. P., Pocock, S., Coope, J., Cutler, J., et al. (1997). Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators. Annals of Internal Medicine, 126, 761-767.
  • Kaplan, N. M. (1994). Hypertension with pregnancy and the pill. In Clinical hypertension (6th ed., pp. 343-365). Baltimore: Williams & Wilkins.
  • Kaplan, N. M. (1995). The treatment of hypertension in women. Archives of Internal Medicine, 155, 563-567.
  • Khaw, K. T., & Peart, W. S. (1976). Blood pressure and contraceptive use. British Medical Journal, 285, 403-407.
  • Kitler, M. E. (1992). Differences in men and women in coronary artery disease, systemic hypertension and their treatment [Editorial]. American Journal of Cardiology, 70, 1077-1080.
  • Laragh, J. H. (1976). Oral contraceptives-induced hypertension—nine years later. American Journal of Obstetrics and Gynecology, 126, 141-147.
  • Lewis, C. E. (1996). Efficacy and tolerance of antihypertensive treatment in men and women with stage I diastolic hypertension: Results of the Treatment of Mild Hypertension Study. Archives of Internal Medicine, 156, 377-385.
  • National High Blood Pressure Education Program Working Group. (2000). Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. American Journal of Obstetrics and Gynecology, 183, S1-S22.
  • SHEP Cooperative Research Group. (1991). Systolic Hypertension in the Elderly Program. Journal of the American Medical Association, 265, 3255-3264.
  • Staessen, J. A. (1997). Randomized double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension (SYST-EUR). Lancet, 350, 757-764.
  • Wassertheil-Smoller, S. (2000). Hypertension and its treatment in postmenopausal women: Baseline data from the Women’s Health Initiative. Hypertension, 36, 780-789.

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