Evaluation of hypertensive patients has three objectives: (1) to assess lifestyle and identify other cardiovascular risk factors or concomitant disorders that may affect prognosis and guide treatment (table 6); (2) to reveal identifiable causes of high BP (table 7); and (3) to assess the presence or absence of target organ damage and CVD.
Patient evaluation is made through medical history, physical examination, routine laboratory tests, and other diagnostic procedures. The physical examination should include: an appropriate measurement of BP, with verification in the contralateral arm; an examination of the optic fundi; a calculation of body mass index (BMI) (measurement of waist circumference is also very useful); an auscultation for carotid, abdominal, and femoral bruits; a palpation of the thyroid gland; a thorough examination of the heart and lungs; an examination of the abdomen for enlarged kidneys, masses, distended urinary bladder, and abnormal aortic pulsation; a palpation of the lower extremities for edema and pulses; and neurological assessment.
Data from epidemiological studies and clinical trials have demonstrated that elevations in resting heart rate and reduced heart-rate variability are associated with higher cardiovascular risk. In the Framingham Heart Study, an average resting heart rate of 83 beats per minute was associated with a substantially higher risk of death from a cardiovascular event than the risk associated with lower heart rate levels. Moreover, reduced heart-rate variability was also associated with an increase in cardiovascular mortality.
No clinical trials have prospectively evaluated the impact of reduced heart rate on cardiovascular outcomes.
Laboratory Tests and Other Diagnostic Procedures
Routine laboratory tests recommended before initiating therapy include a 12-lead electrocardiogram; urinalysis; blood glucose and hematocrit; serum potassium, creatinine (or the corresponding estimated glomerular filtration rate [eGFR]), and calcium; and a lipoprotein profile (after a 9- to 12-hour fast) that includes high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Optional tests include measurement of urinary albumin excretion or albumin/creatinine ratio (ACR) except for those with diabetes or kidney disease where annual measurements should be made. More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved or the clinical and routine laboratory evaluation strongly suggests an identifiable secondary cause (i.e., vascular bruits, symptoms of catecholamine excess, or unprovoked hypokalemia). (See Identifiable Causes of Hypertension for a more thorough discussion.) The presence of decreased GFR or albuminuria has prognostic implications as well. Studies reveal a strong relationship between decreases in GFR and increases in cardiovascular morbidity and mortality. Even small decreases in GFR increase cardiovascular risk.67 Serum creatinine may overestimate glomerular filtration. The optimal tests to determine GFR are debated, but calculating GFR from the recent modifications of the Cockcroft and Gault equations is useful.
The presence of albuminuria, including microalbuminuria, even in the setting of normal GFR, is also associated with an increase in cardiovascular risk. Urinary albumin excretion should be quantitated and monitored on an annual basis in
high-risk groups, such as those with diabetes or renal disease.
Additionally, three emerging risk factors (1) high-sensitivity C-reactive protein (HS-CRP); a marker of inflammation; (2) homocysteine; and (3) elevated heart rate may be considered in some individuals, particularly those with CVD but without other risk-factor abnormalities. Results of an analysis of the Framingham Heart Study cohort demonstrated that those with a LDL value within the range associated with low cardiovascular risk, who also had an elevated HS-CRP value, had a higher cardiovascular event rate as compared to those with low CRP and high LDL cholesterol. Other studies also have shown that elevated CRP is associated with a higher cardiovascular event rate, especially in women. Elevations in homocysteine have also been linked to higher cardiovascular risk; however, the results with this marker are not as robust as those with high HS-CRP.
Identifiable Causes of Hypertension
Additional diagnostic procedures may be indicated to identify causes of hypertension, particularly in patients whose (1) age, history, physical examination, severity of hypertension, or initial laboratory findings suggest such causes; (2) BP responds poorly to drug therapy; (3) BP begins to increase for uncertain reason after being well controlled; and (4) onset of hypertension is sudden. Screening tests for particular forms of identifiable hypertension are shown in table 8.
Pheochromocytoma should be suspected in patients with labile hypertension or with paroxysms of hypertension accompanied by headache, palpitations, pallor, and perspiration. Decreased pressure in the lower extremities or delayed or absent femoral arterial pulses may indicate aortic coarctation; and truncal obesity, glucose intolerance, and purple striae suggest Cushing’s syndrome. Examples of clues from the laboratory tests include unprovoked hypokalemia (primary aldosteronism), hypercalcemia (hyperparathyroidism), and elevated creatinine or abnormal urinalysis (renal parenchymal disease). Appropriate investigations should be conducted when there is a high index of suspicion of an identifiable cause.
The most common parenchymal kidney diseases associated with hypertension are chronic glomerulonephritis, polycystic kidney disease, and hypertensive nephrosclerosis. These can generally be distinguished by the clinical setting and additional testing. For example, a renal ultrasound is useful in diagnosing polycystic kidney disease. Renal artery stenosis and subsequent renovascular hypertension should be suspected in a number of circumstances including: (1) onset of hypertension before age 30, especially in the absence of family history, or onset of significant hypertension after age 55; (2) an abdominal bruit especially if a diastolic component is present; (3) accelerated hypertension; (4) hypertension that had been easy to control but is now resistant; (5) recurrent flash pulmonary edema; (6) renal failure of uncertain etiology especially in the absence of proteinuria or an abnormal urine sediment; and (7) acute renal failure precipitated by therapy with an angiotensin converting enzyme inhibitor (ACEI)
or angiotensin receptor blocker (ARB) under conditions of occult bilateral renal artery stenosis or moderate to severe volume depletion.
In patients with suspected renovascular hypertension, noninvasive screening tests include the ACEI-enhanced renal scan, duplex Doppler flow studies, and magnetic resonance angiography. While renal artery angiography remains the gold standard for identifying the anatomy of the renal artery, it is not recommend for diagnosis alone because of the risk associated with the procedure. At the time of intervention, an arteriogram will be performed using limited contrast to confirm the stenosis and identify the anatomy of the renal artery.
Genetics of Hypertension
The investigation of rare genetic disorders affecting BP has led to the identification of genetic abnormalities associated with several rare forms
of hypertension, including mineralocorticoid-remediable aldosteronism, 11beta-hydroxylase and 17alpha-hydroxylase deficiencies, Liddle’s syndrome, the syndrome of apparent mineralocorticoid excess, and pseudohypoaldosteronism type II. The individual and joint contributions of these genetic mutations to BP levels in the general population, however, are very small. Genetic association studies have identified polymorphisms in several candidate genes (e.g., angiotensinogen, alpha-adducin, beta- and DA-adrenergic receptors, and beta-3 subunit of G proteins), and genetic linkage studies have focused attention on several genomic sites that may harbor other genes contributing to primary hypertension.
However, none of these various genetic abnormalities has been shown, either alone or in joint combination, to be responsible for any applicable portion of hypertension in the general population.