Hypertension is a global health concern, affecting approximately 1.28 billion adults worldwide. In the United States, nearly half of adults aged 18 and older have hypertension, with awareness, treatment, and control rates being suboptimal (40).
Individuals with a family history of hypertension are at a significantly increased risk of developing the condition themselves, owing to both genetic predispositions and shared environmental factors. Comprehensive laboratory testing screens patients with a familial predisposition to hypertension, helping to identify underlying conditions, assess overall cardiovascular risk, and guide personalized treatment strategies.
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What Is Hypertension?
Blood pressure is the force exerted by circulating blood against the walls of the arteries as the heart pumps it throughout the body. It is measured using two numbers:
- Systolic Pressure: represents the pressure when the heart contracts and pumps blood
- Diastolic Pressure: indicates the pressure when the heart is at rest between beats
For example, a blood pressure reading of 120/80 mmHg denotes a systolic pressure of 120 mmHg and a diastolic pressure of 80 mmHg.
Hypertension is defined as sustained elevated blood pressure. According to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, hypertension is diagnosed when systolic blood pressure (SBP) is >130 mmHg or diastolic blood pressure (DBP) is >80 mmHg.
Hypertension is categorized into different stages:
- Normal: <120/80 mmHg
- Elevated: SBP 120-129 mmHg and DBP <80 mmHg
- Stage 1 Hypertension: SBP 130-139 mmHg or DBP 80-89 mmHg
- Stage 2 Hypertension: SBP ≥140 mmHg or DBP ≥90 mmHg
Uncontrolled hypertension significantly increases the risk of:
- Cardiovascular disease (CVD), including peripheral artery disease and heart attack (myocardial infarction)
- Stroke
- Kidney dysfunction, chronic kidney disease (CKD), and kidney failure
- Other complications, such as vision loss and sexual dysfunction
Relevance of Family History in High Blood Pressure
A family history of hypertension significantly impacts the risk and progression of hypertension in individuals. Studies find that genes influence about 35-50% of a person's risk for developing high blood pressure.
The Tampere Adult Population Cardiovascular Risk Study demonstrated that individuals with a positive family history of hypertension had higher systolic and diastolic blood pressures and a greater annual increase in systolic blood pressure over a 15-year follow-up period compared to those without a family history. By age 50, the odds of diagnosed hypertension were significantly higher in those with a positive family history.
The Framingham Heart Study further supports these findings, showing that early-onset hypertension in parents and grandparents increases the risk of hypertension in subsequent generations, even after adjusting for lifestyle factors. This transgenerational risk underscores the importance of considering family history in clinical evaluations.
Additionally, the ACC/AHA guidelines highlight family history as a fixed risk factor for hypertension, necessitating close monitoring and potentially earlier intervention in affected individuals.
Key Lab Tests for Patients With a Family History of Hypertension
These are seven essential laboratory tests necessary for screening, assessing risk, and managing patients with a familial predisposition to hypertension and elevated CVD risk.
Advanced Lipid Profile
A lipid panel measures the levels of various lipids in the blood, including:
- Total cholesterol
- Low-density lipoprotein cholesterol (LDL-C)
- High-density lipoprotein cholesterol (HDL-C)
- Triglycerides
Dyslipidemia is a significant risk factor for atherosclerosis and subsequent CVD. Elevated LDL-C, triglycerides, and low HDL-C contribute to plaque formation and arterial stiffness, exacerbating hypertension and increasing CVD risk. (75)
Abnormal lipid levels guide the initiation and intensity of lipid-lowering therapies, primarily statins. For instance, an LDL-C >190 mg/dL typically warrants high-intensity statin therapy regardless of other risk factors. Elevated triglycerides may necessitate dietary modifications and consideration of fibrate therapy.
Optimal Values
Advanced lipid testing includes measurements beyond the standard lipid profile, such as:
Advanced lipid parameters offer more precise risk stratification for atherosclerotic CVD. Smaller, denser LDL particles are more atherogenic, and elevated ApoB levels correlate with the number of atherogenic lipoprotein particles, providing a better prediction of CVD risk than LDL-C alone. (10, 31)
Patients with elevated ApoB or numerous small, dense LDL particles may benefit from more aggressive lipid-lowering strategies, even if their LDL-C levels are not markedly elevated (3, 54). This could include higher doses of statins or the addition of other emerging lipid-lowering agents, such as ezetimibe or PCSK9 inhibitors, to achieve optimal lipid profiles.
Optimal Values
- LDL Particle Size and Number: fewer, larger particles are preferable
- ApoB: <90 mg/dL (7)
- ApoA1: 167-175 mg/dL (37)
Comprehensive Metabolic Panel (CMP)
The CMP encompasses a group of tests that evaluate metabolic and organ function, including:
- Blood Sugar: glucose
- Electrolytes: sodium, potassium, chloride, calcium, bicarbonate (35)
- Renal Function: blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR) (21)
- Liver Function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) (22)
The CMP provides a broad assessment of metabolic health and helps identify secondary causes of hypertension. The ACC/AHA recommends laboratory measurements, including a CMP, for all patients with a new diagnosis of hypertension to facilitate CVD risk factor profiling, establish a baseline for medication use, and screen for secondary causes of hypertension.
Results from a CMP can influence treatment decisions in several ways. Examples include:
- Abnormal renal function tests (e.g., elevated creatinine) may prompt the use of renal-protective antihypertensives such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
- Electrolyte imbalances, particularly hyperkalemia (high potassium), can influence the choice of diuretics and necessitate dose adjustments.
- Liver dysfunction may require careful selection of medications metabolized hepatically to avoid toxicity.
Hemoglobin A1c (HbA1c)
HbA1c measures glycated hemoglobin, reflecting average blood glucose levels over the past 2-3 months. It is primarily used for diagnosing and monitoring prediabetes and diabetes but also serves as a marker for cardiovascular risk.
Elevated HbA1c is associated with increased hypertension risk, even in non-diabetic individuals (41). Additionally, elevated HbA1c is correlated to dyslipidemia and elevated homocysteine, which collectively raise the risk of CVD, including coronary artery disease (CAD), ischemic heart disease, and ischemic stroke (58). The American Diabetes Association (ADA) notes that an HbA1c range of 5.7-6.4% identifies individuals at high risk for diabetes and cardiovascular outcomes.
Elevated HbA1c levels may prompt more aggressive lifestyle and pharmaceutical interventions, such as dietary changes, increased physical activity, natural supplements, and prescription medications, to reduce blood glucose, blood pressure, and overall CVD risk.
Interpreting Values
- Normal: <5.7%
- Prediabetes: 5.7-6.4%
- Diabetes: ≥6.5% (19)
C-Reactive Protein (CRP)
CRP is an acute-phase reactant produced by the liver in response to inflammation. High-sensitivity CRP (hs-CRP) is a more precise measure used to assess low levels of inflammation, which is relevant for CVD risk assessment. (18)
hs-CRP is an independent predictor of future cardiovascular events, including myocardial infarction and stroke. Elevated hs-CRP levels are associated with increased vascular inflammation, atherosclerosis, and subsequent cardiovascular events. (38, 39)
CVD Risk Stratification Based on hs-CRP Levels
- Low Risk: <1 mg/L
- Average Risk: 1-3 mg/L
- High Risk: >3 mg/L (18)
Several studies, including the JUPITER trial, have shown that reducing hs-CRP levels can significantly impact cardiovascular outcomes. The JUPITER trial demonstrated that statin therapy (rosuvastatin 20 mg/day) in individuals with elevated hs-CRP (>2 mg/L) but normal LDL-C levels resulted in a 44% reduction in the rate of first major cardiovascular events.
This suggests that targeting inflammation through hs-CRP reduction can be beneficial in managing cardiovascular risk. Therefore, in the context of managing patients at risk of hypertension due to family history, elevated hs-CRP levels may prompt the initiation of statin therapy even if LDL-C levels are not elevated.
Thyroid Panel
Both hyperthyroidism and hypothyroidism can lead to elevated blood pressure. Hyperthyroidism increases cardiac output and systolic blood pressure, while hypothyroidism is associated with diastolic hypertension and increased arterial stiffness. (8)
Research has demonstrated a correlation between thyroid disease and hypertension rates. For instance, a study found that thyroid-stimulating hormone (TSH) levels on the high end of normal are associated with increased blood pressure and hypertension risk.
Another study indicated that changes in free T3 (fT3) and free T4 (fT4) levels are independently related to the risk of incident hypertension in a euthyroid population.
Additionally, reduced sensitivity to thyroid hormones has been linked to higher hypertension risk.
A family history of thyroid disease increases the risk of developing thyroid disorders, including autoimmune thyroid diseases like Hashimoto's thyroiditis and Graves' disease. One study found that first-degree relatives of patients with autoimmune thyroid diseases have a significantly higher risk of developing these conditions, with a 16-fold increased risk for children and a 15-fold increased risk for siblings.
Optimal Values
- TSH: 0.5-2.5 mIU/L
- fT4: 1.0-1.7 mIU/L
- fT3: 3.0-4.0 mIU/L
- Anti-TPO: <35 IU/mL (34)
Urinalysis
Urinalysis is a diagnostic test that involves the physical, chemical, and microscopic examination of urine. It provides valuable information about kidney function and can detect various conditions, including infections, kidney disease, and metabolic disorders.
Urinalysis can help identify early signs of kidney damage, such as proteinuria (high protein levels in the urine). Proteinuria, specifically microalbuminuria, can indicate glomerular damage and endothelial dysfunction, which are early features of essential hypertension.
Studies have shown strong correlations between proteinuria/microalbuminuria and hypertension outcomes. For instance, one study concluded that urinary albumin excretion predicts blood pressure progression and incident hypertension in nonhypertensive individuals. Another study found that urinary albumin, even when it is within the normal range, is an independent predictor of future hypertension.
Optimal Values
- Urinary Albumin-to-Creatinine Ratio (UACR): <10 mg/g (63)
Genetic Testing
Polygenic risk scores (PRS) aggregate the effects of numerous single nucleotide polymorphisms (SNPs) to quantify an individual's genetic predisposition to hypertension and CVD. These scores have been shown to improve risk prediction beyond traditional clinical risk factors. The AHA highlights that PRS can identify individuals at high risk for conditions like CAD, high cholesterol, and type 2 diabetes, even when traditional risk factors are not present. (52)
Genome-wide association studies (GWAS) have identified over one thousand SNPs associated with blood pressure control. For example, the MTHFR C677T polymorphism is associated with an increased risk of hypertension and CVD. Individuals with the TT genotype have been shown to have higher blood pressure and increased central hemodynamic parameters compared to those with the CC or CT genotypes.
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Key Takeaways
- Laboratory testing is paramount in managing patients with a family history of hypertension, as it enables early detection, accurate risk stratification, and informed treatment decisions that can mitigate the heightened risk of CVD.
- By adopting comprehensive lab screening protocols, clinicians can effectively identify and address underlying risk factors, ensuring that high-risk populations receive personalized and proactive care.
- Remember that family history is just one of many risk factors for high blood pressure. Regardless of genetic susceptibility, adopting a heart-healthy lifestyle through balanced nutrition, regular physical activity, and stress management can significantly lower the risk of developing high blood pressure, underscoring the importance of a holistic strategy in cardiovascular risk reduction (57).
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