The Newly Identified Hypertensive Patient: Cost‐Effective Laboratory Investigation

A 56-year-old man presented to his physician because of an aching shoulder and was found to have blood pressure (BP) readings of 156/78 mm Hg and 154/82 mm Hg. His physical examination revealed a weight of 101.6 kg, height of 172.7 cm (body mass index, 34 kg/m2), heart rate of 78 beats per minute, and localized tenderness over the left shoulder. Painful abduction was demonstrated and a diagnosis of subacromial bursitis was made. He received a cortisone injection and was asked to return in 2 weeks. The patient otherwise felt well and had not previously seen a physician in many years. At the time of his follow-up visit, the shoulder bursitis had resolved and a repeat BP reading was 152/76 mm Hg. On a weight reduction and regular walking program, his BP 1 month later was 154/82 mm Hg. A review of systems did not reveal any complaints, and the physical examination showed normal optic fundi, normal chest and cardiac examination, no abdominal masses or bruits, and intact peripheral pulses without bruits. He denied an immediate family history of diabetes mellitus and coronary heart disease. Creatinine, lipid profile, glucose, potassium, routine urinalysis, and electrocardiography (ECG) were ordered. At this point, it was reasonable to obtain baseline laboratory testing anticipating initiation of antihypertensive therapy. Although a few more months of attempted lifestyle modification would be an option for a patient with stage 1 BP, chronic hypertension is the best explanation for the observation that serial BPs over 6 weeks did not show any regression to the mean effect. Moreover, his age places him in a class in which additional subclinical cardiovascular comorbidities could define a profile consistent with participants in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), and Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). These trials showed that BP control <140/90 mm Hg within a few months was associated with significantly reduced risk of stroke and myocardial infarction (MI) in patients 55 years and older with additional cardiovascular risk factors. Therefore, laboratory evaluation is indicated at this time while continuing to pursue lifestyle modification and initiation of drug therapy. Professional hypertension societies in the United States, Europe, Great Britain, and Canada have made recommendations regarding the laboratory workup of the newly diagnosed patient with hypertension based on expert consensus. The tone for the US guidelines was established in the first Report of the Joint National Commission on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) in 1977, which stated, “The evaluation of patients with high BP can be limited to a few baseline tests in most instances,” in spite of the fact that “extensive laboratory testing of patients with high BP has been advocated in many medical centers.”1Table I shows that testing recommended by the JNCs from 1977 through 2003 have been modified minimally to include evaluation of glycemic and lipid status. The British Hypertension Society (BHS), Canadian Hypertension Society (CHS), and European Hypertension Society (ESH) have published similar recommendations,2–4 although the ESH list is more expansive, particularly with an added list of “recommended tests” (Table II, Table III, and Table IV). Most of the core tests are readily defensible, particularly the lipid profile, glucose, creatinine, 12-lead ECG, sodium, potassium, and urinalysis for protein and red blood cell detection. Dyslipidemia is more common in untreated hypertensives than normotensives, and lipid levels increase as BP increases.5,6 In the Multiple Risk Factor Intervention Trial (MRFIT), participants with both the highest systolic BP and the highest lipid levels had the highest rate of fatal MI.6 Lowering low-density lipoprotein levels with well-tolerated statin agents to goal levels <100 mg/dL may be at least as powerful a tool in reducing coronary heart disease mortality as lowering the systolic pressure.7 Unfortunately, according to one study, although 50% of hypertensive patients had dyslipidemia, only about 30% were treated and <10% achieved lipid levels consistent with National Cholesterol Education Program II (NCEP II) guidelines.8 While a fasting lipid panel to assess hypertriglyceridemia is optimal for the newly identified patient with hypertension, a nonfasting specimen will suffice in many cases given the more difficult practicality of obtaining a specimen following a 14-hour fast. For this particular patient, the lack of a positive family history of early coronary disease would make an elevated triglyceride level less significant and limit current treatment recommendations unless it was >1000 mg/dL.9 The patient described has 3 risk factors for diabetes mellitus: (1) age older than 45 years, (2) body mass index (BMI) ≥25 kg/m2, and (3) hypertension,10 which is a common triad. Most individuals with new-onset hypertension are older than age 45 years. Hypertension registry data from Kaiser Permanente in California has shown that 89% of 1.2 million adults with hypertension in this registry are older than age 45 years.11 The mean BMI for >42,000 ALLHAT participants was 29.7 kg/m2. When considering screening tests for large populations, however, cost-effective analysis is worthwhile. A Markov model analysis considered targeted screening for type 2 diabetes mellitus for patients with hypertension recommended by the 2003 US Preventative Services Task Force. In 1997 US dollars, a $24 expense for each hypertensive patient screened with a fasting glucose would cost $87,096 for 1 quality-adjusted life year (QALY) starting at age 35, and $46,881 for 1 QALY starting at age 45. The authors recommended screening limited to hypertensive patients aged 55 to 75 years at a cost of $34,375 for 1 QALY.12 The glucose obtained is ideally in the fasting state, but again, given practicalities of patient adherence, a random glucose obtained at least 2 hours following last oral intake other than water could suffice. Renal status is important to assess with regard to (1) estimating global cardiovascular risk, (2) deciding goal BP, (3) ruling out primary renal disease as a cause of hypertension, and (4) establishing a baseline before initiating antihypertensive therapy, which may affect renal function. Dipstick proteinuria indicative of urinary protein ≥300 mg/dL or routine urinalysis showing red blood cells could be a sign of primary glomerulonephritis as the etiology of hypertension, and if reproducible, even with normal renal function, would call for a BP treatment goal <130/80 mm Hg. Serum creatinine with an added calculation of glomerular filtration rate based on the Modification of Diet in Renal Disease (MDRD) formula contributes to the estimate of global cardiovascular risk13 and also helps decide goal BP and the possibility of primary renal disease. Should determination of microalbuminuria replace dipstick assessment of proteinuria when evaluating the newly identified patient with hypertension? Microalbuminuria measurement is considered “routine” by EHS and “optional” by the JNC. A cost-effective analysis showed a cost of $18,621 per QALY.14 While probably adding additional information to the global cardiovascular risk profile, however, a microalbuminuria measure in place of a simple dipstick urinalysis does not alter management, is more costly, and is less universally available. Baseline potassium is necessary before initiation of antihypertensive therapy, which is likely to include a diuretic as well as an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Diuretic-related hyponatremia is more likely to occur in thin elderly women, and therefore a baseline serum sodium may also be a targeted test for women aged 70 years and older as well as for patients taking chronic selective serotonin-reuptake inhibitors, which may cause hyponatremia. For controlled stable hypertension patients, JNC 7 recommends at least a yearly determination of potassium and creatinine. A baseline ECG is important to assess subclinical cardiac disease, because asymptomatic coronary artery disease would change medication management and alter goal BP. Silent MIs by ECG made up 25% of total MIs and were as likely to lead to death, heart failure, and stroke as clinical MIs in both the Framingham Heart Study15 and the Multiple Risk Factor Intervention Trial (MRFIT).16 In MRFIT, 1.2% of the 12,866 male patients aged 35 to 57 years, of whom 62% were included in that study due to diastolic hypertension, had ECG evidence of subclinical MI. MI is a compelling indication for a β-blocker because of proven mortality reduction in this setting. Without a compelling indication, current recommendations are to move β-blockers to third or fourth place in routine hypertension management drug sequences. According to recent consensus American Heart Association guidelines, a goal BP <130/80 mm Hg is recommended for patients with known coronary artery disease.17 While ECG determination of left ventricular hypertrophy using the Cornell/strain index is a common finding in patients with hypertension, occurring in 16.3% in one survey,18 this finding does not alter current hypertension management recommendations for either goal BP or therapy. Additional testing also appears on some of the guideline lists: hematocrit, uric acid, calcium, echocardiography, and inflammatory markers such as C-reactive protein. Baseline hematocrit measurement is recommended by the JNCs 1 through 7, CHS, and EHS, but not the BHS. The original justification was an association of some erythrocytosis conditions with hypertension, particularly polycythemia vera. While screening hematocrit level, in general, has contributed to the early detection of polycythemia vera, clinical signs and symptoms leading to diagnosis in a major hematology text do not include hypertension.19 Diagnosing polycythemia vera because of new-onset stage 1 or lower level stage 2 hypertension (<180/110 mm Hg) in the absence of plethora or significant malaise is extremely rare. In addition, baseline hematocrit measurement might be a consideration because angiotensin-converting enzyme inhibitors and angiotensin receptor blockers might lower hematocrit levels slightly, but, in the presence of normal renal function, that decrease is seldom of clinical significance.20 Although hyper-uricemia might be a pathogenetic factor in essential hypertension,21 lowering uric acid has not been convincingly shown to add to hypertension treatment. While the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial22 analysis attributed a 29% reduction in MIs to the uricosuric effect of losartan compared with atenolol, a more convincing case has been made for higher central aortic pressure compared with similar brachial pressures as an explanation for the reduced benefit of β-blockade compared with alternative agents in the initial treatment of hypertension.23 Furthermore, baseline asymptomatic hyperuricemia is not a contraindication to low-dose thiazide therapy. Serum calcium was not on the JNC VI list of recommended laboratory investigations for newly diagnosed hypertension but is included in the JNC 7 recommendations. It is not included in the BHS, CHS, or ESH lists of recommended tests. While primary hyperparathyroidism is associated with hypertension, parathyroidectomy is not expected to cure hypertension in these cases. Hypercalcemia due to primary hyperparathyroidism is a thiazide contraindication but is rare, and a cost-effective analysis of routine test ordering for all patients with hypertension has not been performed. Obtaining a serum calcium value may be more ideally positioned further down the line for resistant cases. Detection of inflammatory markers such as C-reactive protein does not influence the clinical management of hypertension. Routine echocardiography is not cost-effective and does not affect hypertension management.24 This case brings attention to clinical utility and cost-effective management of routine laboratory investigation of patients with newly diagnosed hypertension. For an asymptomatic patient with new-onset stage 1 or lower level stage 2 hypertension (<180/110 mm Hg), a serum creatinine, lipid profile (preferably fasting), glucose (preferably fasting), potassium, routine urinalysis, and ECG are clinically justifiable and cost-effective.

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