V. Routine and Optional Laboratory Tests for the Investigation of Patients with Hypertension

Diagnosis and Assessment

Subgroup Members: Thomas Wilson, MD; S. Brian Penner, MD; Ellen Burgess, MD; Praveena Sivapalan, MD
Central Review Committee: Stella S. Daskalopoulou, MD, PhD; Kaberi Dasgupta, MD, MSc; Kelly B. Zarnke, MD, MSc; Kara Nerenberg, MD, MSc; Alexander A. Leung, MD, MPH; Kevin C. Harris, MD, MHSc; Kerry McBrien, MD, MPH; Sonia Butalia, BSc, MD; Meranda Nakhla, MD, MSc
Chair: Doreen M. Rabi, MD, MSc

This information is based on the Hypertension Canada guidelines published in Leung, Alexander A. et al. Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol 2017; 33(5): 557-576.


  1. Routine laboratory tests that should be performed for the investigation of all patients with hypertension include:
    1. Urinalysis (Grade D);
    2. Blood chemistry (potassium, sodium, and creatinine) (Grade D);
    3. Fasting blood glucose and/or glycated hemoglobin (A1c) (Grade D);
    4. Serum total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), non-HDL cholesterol, and triglycerides (Grade D); lipids may be drawn fasting or non-fasting (Grade C).
    5. Standard 12-lead electrocardiography (Grade C).
  2. Assess urinary albumin excretion in patients with diabetes (Grade D).
  3. All treated hypertensive patients should be monitored according to the current Diabetes Canada guidelines for the new appearance of diabetes (Grade B).
  4. During the maintenance phase of hypertension management, tests (including those for electrolyte, creatinine, and fasting lipids) should be repeated with a frequency reflecting the clinical situation (Grade D).


1. Routine laboratory tests that should be performed for the investigation of all patients with hypertension include:

i. Urinalysis (Grade D);

ii. Blood chemistry (potassium, sodium, and creatinine) (Grade D);

iii. Fasting blood glucose and/or glycated hemoglobin (A1c) (Grade D);

iv. Serum total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), non-HDL cholesterol, and triglycerides (Grade D); lipids may be drawn fasting or non-fasting (Grade C).

v. Standard 12-lead electrocardiography (Grade C).

There is little direct evidence on which to base recommendations for laboratory testing. Thus, the recommended tests have been based largely on expert opinion. However, the routine laboratory investigations are recommended for the following reasons. First, abnormalities in these tests are common. For example in the Prospective Cardiovascular Muenster (PROCAM) study, 20% of subjects with hypertension had hyperlipidemia and 10% had diabetes mellitus (1). Second, the screening for abnormal serum biochemistry ensures appropriate selection of drug therapy when necessary. For example, caution is warranted if diuretic therapy is considered for patients with hypokalemia or if an angiotensin-converting enzyme (ACE) inhibitor is considered for patients with elevated creatinine levels. Third, these investigations also aid in the determination of the risk of cardiovascular disease for patients with hypertension based on the presence or severity of concomitant vascular risk factors. As such, the results may shorten the diagnostic phase (if target organ damage is present), define a higher risk group or affect the choice of first-line therapy. For example, an EKG may reveal the presence of left ventricular hypertrophy (LVH) or a prior myocardial infarction, both of which portend a higher risk of future cardiovascular events and death (2,3). Finally, both the routine and optional investigations aid in the screening for some of the modifiable causes of hypertension. For example recurrent and/or severe hypokalemia may indicate the presence of primary hyperaldosteronism.

When compared with oral glucose tolerance testing, a systematic review suggests that A1C and fasting glucose levels demonstrate comparable sensitivity and specificity for diabetes detection (4). In a more recent analysis of more than 2000 adults at high risk for diabetes, Hu and colleagues determined the sensitivity and specificity for diabetes of A1C and fasting glucose to be virtually identical (about 80%) at the thresholds evaluated. In addition, when both tests were combined, sensitivity (96.5%) and specificity (96.3%) increased (5). The addition of A1C harmonizes the CHEP recommendations with those of the Canadian Diabetes Association (6).

Duration of fasting (from 1 to > 16 hours) had little association with measured cholesterol levels in a large Canadian community-based cross-sectional study of 209,180 individuals (7). Total cholesterol varied by < 2% (with an average of 4.3 mmol/ L after 1 hour of fasting compared with 4.5 mmol/L after a prolonged fast of 16 hours). Similarly, HDL cholesterol varied by < 2% (from 1.2 to 1.3 mmol/L) and LDL cholesterol by < 10% (from 2.3 to 2.6 mmol/L). These findings are consistent with those of other studies (8,9).

Multiple studies have shown that nonfasting lipid levels are predictive of incident cardiovascular disease (8-13). A Danish cohort of 9319 individuals was followed prospectively for 14 years (9), and individuals in the highest tertile of nonfasting total cholesterol were at increased risk for cardiovascular events compared with those in the in the lowest tertile (HR, 1.7; 95% CI, 1.1-2.6) with similar findings also seen for non- HDL cholesterol (HR, 2.3; 95% CI, 1.5-3.4) and LDL cholesterol (HR, 2.1; 95% CI, 1.4-3.1). In another study, on the basis of the National Health and Nutrition Examination Survey (NHANES) III, 4299 pairs of fasting and nonfasting individuals (matched 1:1) were followed for a mean of 14 years. Regardless of whether LDL cholesterol was collected fasting or nonfasting, the levels were similarly predictive of cardiovascular mortality as well as all-cause mortality in a dose-dependent manner. This remained true for individuals with and without diabetes (8). Furthermore, using a centralized database of over 125 prospective studies, the Emerging Risk Factors Collaboration conducted a study of 302,430 participants (with a mean age of 58 years representing 2.79 million person-years at risk) and reported similar associations between death attributable to coronary heart disease and lipid levels (for HDL, non-HDL, and LDL), irrespective of fasting status (12).

From a practical standpoint, performing nonfasting lipid assessments in routine clinical care might obviate many of the serious challenges associated with prolonged fasting, namely the possibility of decreased patient adherence, increased laboratory burden due to bolus testing in the morning, and preventable hypoglycemia among individuals with diabetes (14-16).

2. Assess urinary albumin excretion in patients with diabetes (Grade D).

Assessment of urinary albumin excretion is no longer used as a basis for targeting lower BP, but is used to guide treatment of hypertension in association with diabetes mellitus. If albuminuria is present, therapy with a renin angiotension system blocker (ACE inhibitor or angiotensin receptor antagonist) is indicated (please see relevant treatment recommendation for further details) (17,18).

In patients without diabetes, urine albumin to creatinine ratio (ACR) is not recommended. Although an independent predictor of future cardiovascular events (19-21), the evidence is not considered strong enough at this time to recommend routine screening of urine albumin levels in people with hypertension who do not have diabetes.

3. All treated hypertensive patients should be monitored according to the current Diabetes Canada guidelines for the new appearance of diabetes (Grade B).

The Canadian Diabetes Association guidelines can be found online (www.guidelines.diabetes.ca). In part, hypertensive patients are at higher risk for developing type 2 diabetes because of the tendency of cardiometabolic risk factors to cluster, particularly with central adiposity (22-24). At minimum, new-onset diabetes occurs in 1% to 2% of hypertensive patients per year (25,26) and is independent of the type of antihypertensive therapy (27). Among 18,411 nondiabetic hypertensive patients 55 years of age or older who had follow-up measurements of fasting plasma glucose (43% of the original cohort), the cumulative incidence of diabetes was 8% to 11% at four years (27). Furthermore, the prognosis of patients who develop diabetes is worse than those who do not (25-29). After 14.3 years of follow-up in the placebo arm of the Systolic Hypertension in Elderly Patients (SHEP) trial (28) (age older than 60 years), there was a significant increase in the cardiovascular mortality (hazard ratio [HR] 1.56; 95% CI 1.12 to 2.18) and total mortality (HR 1.35; 95% CI 1.05 to 1.73) among those who developed diabetes.

Although based on weaker evidence, the type of antihypertensive drug treatment also appears to influence future risk of type 2 diabetes (22,23). Studies suggest that both beta-blockers and thiazides are associated with an increased risk of diabetes, and angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers are neutral or associated with decreased risk (22). However, in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial (30) (three-year randomized controlled trial involving 5269 prediabetic patients), ramipril did not significantly reduce the incidence of type 2 diabetes (HR 0.91, 95% CI 0.81 to 1.03) or mortality. Thus, no specific antihypertensive drugs are currently recommended to prevent the development of diabetes mellitus. It is important to note that there are currently no conclusive data that directly implicate drug-induced type 2 diabetes with increased cardiovascular risk (28). Furthermore, in patients with or without diabetes, thiazide-based treatment regimens reduce cardiovascular and overall mortality to a similar extent as ‘nondiabetogenic’ agents (31). The task force will continue to monitor this area closely and issue updated recommendations as required.

4. During the maintenance phase of hypertension management, tests (including those for electrolyte, creatinine, and fasting lipids) should be repeated with a frequency reflecting the clinical situation (Grade D).

Follow-up lab testing may be indicated to monitor for adverse effects of antihypertensive treatment, as surveillance for the development of end-organ damage and/or to re-stratify cardiovascular risk. The need for such testing differs across hypertensive patients and, in the absence of specific studies to define the optimal testing frequency, is left to the judgment of individual clinicians.


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