Blood Pressure Medication At 27

Hypertension affects one-quarter of the global population and is the leading modifiable risk factor for cardiovascular disease and mortality.¹ Previously, treatment has tended to focus on individuals in whom the 10-year risk of cardiovascular events is the greatest, with increasing age being a strong factor. However, the presence of hypertension at a young age increases the risk of cardiovascular events in middle age.² It contributes to an earlier onset of coronary heart disease, heart failure, stroke, and transient ischemic attacks.³ Although good national guidelines exist, they do not serve low-risk young patients with hypertension as effectively as older patients. Furthermore, risk assessment is challenging in young patients because of limited validity and a focus on systolic blood pressure (SBP) that is less well correlated with cardiovascular end points.^2,4

The definition of young in guidelines varies as below the age of 50, 40, and 30 years.^5–7 Worldwide estimates of the prevalence of hypertension in the year 2000 among adults aged 20 to 29 years were 12.7% in men and 7.4% in women rising to 18.4% and 12.6%, respectively, in 30- to 39-year olds.⁸ The estimated prevalence of hypertension among those aged 18 to 39 years in the United States (2011–2012) was 7.3%.⁹ Both studies defined hypertension as an average blood pressure of >140/90 mm Hg or the use of antihypertensive medication. More recently, the definition of hypertension has been expanded by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Hypertension Clinical Practice Guidelines to include blood pressure above 130/80 mm Hg, and thus the prevalence of hypertension by this criterion is likely far greater than that reported above. Moreover, in selected populations, the prevalence of hypertension may be even higher, for example blacks have a 2-fold higher risk of hypertension compared with whites, as well as lower rates of blood pressure control.¹⁰

Blood pressure in adulthood may also be determined by factors occurring many years earlier.¹¹ Barker et al¹² proposed the Developmental Origins of Health and Disease hypothesis whereby the lifetime trajectory of BP is programmed in the perinatal period. Although fetal growth restriction may play some role, other factors such as genetic and environmental influences are probably more significant.¹³ This is supported by studies demonstrating higher BP in adolescents whose mothers had experienced hypertensive disorders of pregnancy and higher rates of antihypertensive prescriptions to young adults born preterm.^14–16 Similarly, alterations in the cardiovascular system of those born prematurely or of low birth weight are well documented.¹⁷ Risk factors for young-onset hypertension have been explored through several large studies (summarized in Table S1 in the online-only Data Supplement).

Hypertension can have harmful health effects even at a young age. In the short term, it is associated with higher rates of left ventricular hypertrophy¹⁸ and alterations in brain volume and white matter hyperintensity volume, suggesting that hypertension in young adults may impact cardiovascular and brain health.^19,20 The Strong Heart Study assessed clinical and echocardiographic features in 1940 native Americans aged 14 to 39 years. Individuals with prehypertension (blood pressure, 120–139/80–89 mm Hg) and hypertension (blood pressure ≥140/90 or use of antihypertensive medications) had higher rates of left ventricular hypertrophy than normotensive individuals of the same age.¹⁸ In the long term, multiple studies have demonstrated increased rates of cardiovascular disease and mortality in young people with hypertension.^2,3,21 Furthermore, blood pressure has been shown to strongly track with age meaning that individuals with elevated blood pressure in youth are likely to have elevated blood pressure in later life.¹¹ Sundstrom et al² using data from 1.2 million Swedish men (mean age, 18 years) conscripted into military service between 1969 and 1995 demonstrated a direct correlation between baseline blood pressure and cardiovascular mortality at follow-up. The CARDIA longitudinal study (Coronary Artery Risk Development in Young Adults) has been important in exploring the contribution of early-life risk factors to the development of coronary heart disease in later life using a cohort of 5115 young adults in the United States aged 18 to 30 years.^3,22 They showed that elevated SBP at baseline was more predictive of coronary artery calcium 15 years later than the risk factor profile at point of follow-up.²² Additionally, a retrospective analysis of CARDIA data demonstrated a significantly higher risk of cardiovascular disease among hypertensives (defined by 2017 ACC/AHA guidelines) compared with normal blood pressure (<120/80 mm Hg) in individuals below the age of 40 years at baseline.³

This shows the impact of early-life risk factors on long-term health and implies that it may not be appropriate to defer addressing cardiovascular health until middle age. This is important because hypertensive patients below the age of 40 years have lower awareness, slower diagnosis rates, and poorer blood pressure control than older individuals.^9,23,24 A recent study identified wide-ranging barriers to good blood pressure control in young adults.²⁵ These included psychosocial themes (eg, concerns regarding the projection of a sick identity upon young adults) and management concerns (eg, appropriate drug treatment of women of childbearing potential). Many respondents were concerned about the benefits and risks of treatment, fear of misdiagnosis (and potential impact on life insurance), adherence, follow-up, and resource allocation. These issues have been discussed extensively, with concerns expressed by primary care physicians that new national guidelines could lead to overdiagnosis and overtreatment.^26,27

Defining Blood Pressure Thresholds for Hypertension in Young People

The ACC/AHA lowered the diagnostic threshold for stage 1 hypertension in the 2017 Guidelines from 140/90 to 130/80 mm Hg across all age categories to some controversy, not least because it increased the prevalence of hypertension in the US population to 46%.^7,26,28 This change in threshold was based on a systematic review of 10 studies,²⁹ the largest of which was SPRINT (Systolic Blood Pressure Intervention Trial).²⁸ The mean age of participants in the systematic review ranged from 36 to 77 years with only 1 small study having a mean age at entry of <40 years and only 4 recruiting any participants aged under 50 years.³⁰

Should we pay more attention to SBP or diastolic blood pressure (DBP) in young people? Sundstrom et al² used data from 1.2 million Swedish men conscripted into military service between 1969 and 1995. All men underwent a medical at entry, and blood pressure was recorded in a standardized way; there was a clear correlation between baseline blood pressure and cardiovascular mortality at follow-up. DBP was more strongly correlated to all-cause mortality than SBP, with risk rising substantially above 90 mm Hg. Hazard ratios were 1.02 (0.99–1.05) and 1.35 (1.26–1.45), respectively. Furthermore, diastolic hypertension is more common among patients under the age of 50 years (62.5% compared with 42% in over 50s).³¹

Additionally, there is uncertainty regarding the significance of isolated systolic hypertension in the young (SBP ≥140 mm Hg, DBP <90 mm Hg). Less than 20% of untreated hypertensives below the age of 40 years have isolated systolic hypertension, compared with 80% of over 50s.³¹ Isolated systolic hypertension in young people may represent increased pulse wave amplification rather than increased aortic stiffness, meaning that in many cases, young adults with high brachial systolic pressures have normal central aortic pressure.³² However, McEniery et al³³ identified no difference in pulse wave amplification between isolated systolic hypertension patients and normotensives aged 17 to 27 years but demonstrated either increased stroke volume or increased aortic pulse wave velocity suggesting isolated systolic hypertension may not be a benign state in young people. More recently, Yano et al²¹ noted among a cohort of 27 081 individuals from Chicago (mean age, 33, ±SD, 9 years; 39% hypertensive) that isolated systolic hypertension imparts increased risk of cardiovascular mortality compared with optimal blood pressure (<130/85 mm Hg); adjusted hazard ratio for men was 1.23 (95% CI, 1.03–1.46) and 1.55 for women (95% CI, 1.18–2.05).

Finally, a recent retrospective analysis of data derived from the CARDIA study sought to identify whether young-onset hypertensives defined using the 2017 ACC/AHA guidelines had increased cardiovascular events.³ This showed a higher rate of cardiovascular events for mildly elevated blood pressure (SBP, 120–129 mm Hg; DBP, <80 mm Hg) and stage 1 hypertension (SBP, 130–139 mm Hg or DBP, 80–89 mm Hg). However, all-cause mortality was not significantly elevated.

What Is the Optimal Approach to High Blood Pressure in Young Adults?

Broadly, the management of young-onset hypertension is the same as that of older individuals, but distinctions are made regarding investigation and referral strategies. Table 1 sets out a summary of the American, European, and British guidelines with respect to the management of hypertension in young adults. They differ in their classification of blood pressure and varied use of risk-based thresholds for treatment. We address 3 key questions:

**Table 1.** ACC/AHA, ESC, and NICE (UK) Guidelines for the Management of Hypertension With Special Emphasis on Care of Young Patients
Office Blood Pressure	120–129/<80	SBP, 130–139 or DBP, 80–89	SBP ≥140 or DBP ≥90	BP ≥160–179/100–109	SBP ≥180 or DBP ≥110
Classification
ACC/AHA (2017)	Elevated	Stage 1	Stage 2	Stage 2	Stage 2
ESC (2018)		High normal	Grade 1	Grade 2	Grade 3
NICE NG136 (2019)			Stage 1	Stage 2	Severe
Treatment threshold
ACC/AHA (2017)	Lifestyle	Treat if CVD or a 10-y ASCVD* risk >10%	Treat	Treat	Treat
ESC (2018)		Lifestyle advice but treat if high risk	Low-moderate risk: treat if lifestyle fails. High risk: treat	Treat	Treat
NICE NG136 (2019)			OD/CVD, diabetes mellitus, or 10-y CV risk >10%	Treat	Treat
Specialist referral
ACC/AHA (2017)	Suspected secondary HTN particularly primary aldosteronism
ESC (2018)	Suspected secondary HTN. Follow-up of hypertensive emergencies. Resistant HTN. Detailed assessments of organ damage
NICE NG136 (2019)	Accelerated HTN (≥180/110) with papilledema or retinal hemorrhages, suspected secondary HTN
Considerations for young patients
ACC/AHA (2017)	Young, <30 y. Consider screening for primary aldosteronism. Optimal point of intervention is not clear.
ESC (2018)	Refer under 40 s with grade 2 HTN or greater. Treatment of uncomplicated grade I HTN may be considered prudent. Unclear whether ISH should be treated.
NICE NG136 (2019)	Young-onset hypertension is <40. Risks are underestimated. Refer to allow detailed assessment of organ damage. ISH to be treated as per older individuals.

How Should Young Adults With Hypertension Be Investigated?

Investigation in young adults is advocated across American, European, and British guidelines for the identification of secondary causes of hypertension and evidence of organ damage.^5–7 Predictors of a secondary cause for hypertension include young age (<30 years) with no other risk factors, drug resistant hypertension, severe hypertension (>180/110 mm Hg), sudden deterioration in blood pressure control, nondipping status on ambulatory blood pressure monitoring, or the presence of hypertension-mediated organ damage.³⁴ Recognizing secondary causes of hypertension is potentially beneficial, as this might direct specific treatment strategies and potentially cure high blood pressure in young patients. This is especially important in young people where the sustained duration of high blood pressure on organs such as the brain and kidneys may produce irreversible changes. Furthermore, the identification and treatment of secondary hypertension below the age of 40 years is associated with better blood pressure control.³⁵

This beneficial impact needs to be balanced against the risks such as cost, patient burden, and incidental diagnoses from imaging investigations. Both the European and British guidelines state that secondary forms of hypertension are more common among young adults with high blood pressure and more likely to be detected,^5,6 making a case to meet incurred costs through specific treatment gains. However, 1 study showed that young adults were less likely to have a recognized underlying cause than older patients, with prevalence ranging from 5.6% in the 18- to 29-year age group, 8.1% in the 30- to 39-year age group, and 17.4% in the over 70s.³⁶ The most common causes of secondary hypertension among young adults were hypothyroidism (1.9%), renovascular disease (1.7%), renal insufficiency (1.5%), primary hyperaldosteronism (1.2%), Cushing syndrome (0.5%), and pheochromocytoma (<0.3%). Renovascular disease was caused predominantly by fibromuscular dysplasia in 18- to 29-year olds (89%) and atherosclerosis in 30- to 39-year olds (61%).

An ECG is recommended to identify evidence of left ventricular hypertrophy alongside serum creatinine and microalbuminuria to evaluate for subclinical renal damage.⁵ However, ECG assessment has limited sensitivity for identifying left ventricular hypertrophy, and, therefore, the European guidelines recommend an echocardiogram.⁶ Cardiac magnetic resonance imaging is more sensitive and specific than echocardiography at identifying left ventricular hypertrophy and may be used to simultaneously evaluate for secondary causes of hypertension.³⁷ Renal ultrasound and computerized tomographic angiography are established modalities for screening for renal and renovascular disease.³⁴

Is a Risk-Based Approach Appropriate in Young Adults With Hypertension?

All 3 guidelines utilize 10-year cardiovascular models to provide thresholds for the initiation of antihypertensive therapy (Table 1). Basing treatment on overall cardiovascular risk rather than specific blood pressure levels is supported by 2 meta-analyses focused on cardiovascular risk reduction in middle-aged and older individuals.^38,39 However, other authors have pointed to reports of overestimation of risk and lack of validity for using risk scores in this way.^26,27 Risk-based approaches can be problematic in the young because absolute 10-year cardiovascular risk is often low, irrespective of other risk factors, despite a substantially increased lifetime risk of cardiovascular events.

In this respect, the ACC/AHA guidelines are helpful as they advocate treating all stage 2 hypertensives (SBP >140 and DBP >90 mm Hg) regardless of 10-year cardiovascular risk.⁷ When considering stage 1 hypertension (SBP, 130–139 or DBP, 80–89 mm Hg), they advise treating those with atherosclerotic cardiovascular disease, estimated 10-year cardiovascular risk ≥10%, or the presence of diabetes mellitus or chronic kidney disease. However, the atherosclerotic cardiovascular disease risk score was validated on data derived from people aged 40 to 79 years, so it may be less applicable to younger patients.⁴⁰ The European Guidelines for Cardiovascular Disease Prevention suggest the use of relative risk tables and heart age calculation (using the Systematic Coronary Risk Evaluation system).⁴¹ The validation window for Systematic Coronary Risk Evaluation is 40 to 65 years, and in contrast to the atherosclerotic cardiovascular disease, which predicts mortality, Systematic Coronary Risk Evaluation assesses the risk of a first fatal atherosclerotic event.⁶

The European guidelines highlight the lack of evidence for blood pressure–lowering therapy in the young while acknowledging the epidemiological evidence of harm from higher blood pressure. Therefore, they suggest consideration of treatment to avoid more severe hypertension and the development of hypertension-mediated organ damage.⁶ In the United Kingdom, the National Institute for Health and Care Excellence recommends treatment of those with SBP of 140 to 159 mm Hg or DBP of 90 to 99 mm Hg with evidence of target organ damage or in those free of cardiovascular disease with a 10-year cardiovascular event risk of >10%.⁵ In the United Kingdom, QRISK2 is the preferred 10-year risk assessment tool but was validated on 35- to 74-year olds.⁴² The latest version of QRISK3 has been extended to 25 to 84 years of age and includes relative risk, heart age, and lifetime risk calculation.⁴³

How Should Young-Onset Hypertension Be Treated?

Epidemiological data suggest that blood pressure reduction at a population level is beneficial. The close tracking of blood pressure from early adulthood to later life and the finding of cardiovascular and brain changes in young adults with hypertension support the argument that young people with high blood pressure should be treated in the same way as older adults. However, there is an absence of data assessing pharmacological intervention in this young age group. Lifestyle interventions to address the risk factors are recommended. A recent systematic review and meta-analysis of 14 exercise studies in 18- to 40-year olds showed that supervised exercise programs improve clinic blood pressure by an average of 4 to 5 mm Hg at 3- to 6-month follow-up, but the blood pressure–lowering benefits were not sustained at 12 months.⁴⁴ Furthermore, higher intensity programmes associated with >4 kg weight loss had greater benefits. Weight loss was found to have a greater impact on blood pressure compared with metoprolol treatment in young overweight patients (age, <50 years).⁴⁵ More research is required on how to sustain the short-term benefits of exercise, weight loss, and other lifestyle interventions in this young population.

Several meta-analyses have shown that thiazide diuretics, calcium channel antagonists, ACE (angiotensin-converting enzyme) inhibitors, angiotensin receptor blockers (ARB), and β-blockers are equally effective in reducing cardiovascular events in older individuals and younger individuals below the age of 65 years.^46–48 This finding is reflected across the European and ACC/AHA hypertension guidelines that do not advocate a specific starting agent out of those drug classes. NICE, in contrast, advocates an age-based algorithm whereby an ACE inhibitor or ARB is recommended first line for those below 55 years of age except for people of black African or African-Caribbean family origin in whom calcium channel antagonists are recommended.⁵ The reason for this age-based approach is due to 2 crossover studies that pointed to individuals below the age of 55 being more responsive to ACE inhibitors and β-blockers than calcium channel antagonists and diuretics.^49,50 Where pharmacological management is indicated, clinicians should consider ethnicity, sex, and comorbidity (in keeping with older individuals).

While national guidelines do not recommend different treatment of men and women, it is important to consider pregnancy potential in women for several reasons. First, poor control of chronic hypertension during pregnancy increases the risk of preeclampsia, and good blood pressure control before pregnancy is beneficial.⁵¹ Second, ACE inhibitors and ARBs in women of childbearing age should be avoided during pregnancy because of risk of adverse fetal outcomes.^6,52 Those already taking ACE inhibitors or ARBs should be counseled of the fetal risks in pregnancy and consider switching to alternative antihypertensives such as labetalol, nifedipine, or methyl dopa if they are planning to conceive.⁵² It is also important to consider that ≤50% of pregnancies are unplanned, so ACE inhibitors and ARBs should be withdrawn promptly upon awareness of pregnancy and alternative agents offered.

What Are the Gaps in Evidence?

This review has identified a number of areas where more evidence is needed to guide clinicians who manage young people with hypertension. While it is clear that high blood pressure in young adults has important detrimental consequences in later life, there is limited evidence whether interventions can reduce the risk of cardiovascular events or adverse changes in brain structure. Randomized controlled trials of interventions are urgently needed to answer this question as the number of young adults worldwide with hypertension increases. Progress has been made to make risk scores more relevant to young adults, including the use of lifetime risk and heart age scores. DBP may be important to include in risk assessment. However, a change from 10-year cardiovascular risk to lifetime risk would have implications for the number of people becoming eligible for intervention. The risks and benefits of this approach need to be explored further. How this is best communicated to improve shared decision-making and increase persistence of lifestyle changes over time also warrants further investigation. As a previously untreated cohort of young adults with hypertension are offered pharmacological interventions, we are still not sure whether the drugs that are effective in older people are as efficacious in young people. Therefore, studies comparing different treatment strategies in young-onset hypertension are needed.

Conclusions

Young-onset hypertension is a common condition that increases all-cause mortality and results in subclinical organ damage early in its natural history. Epidemiological studies suggest that early-life factors are important and should be addressed by public health policies to reduce cardiovascular disease later in life. Although higher blood pressure in young people tracks with blood pressure later in life and is associated with adverse short- and medium-term cardiovascular outcomes, the absence of randomized trials of blood pressure lowering in young adults means the safety and efficacy of antihypertensive therapy in mild grades of hypertension are unknown.

Referral of selected patients to secondary care (Table 2) is suggested as it permits more detailed assessment, evaluation of subclinical organ damage, and investigation of secondary causes of hypertension (Table 3). This can allow more personalized management given the limitations of current risk-based approaches in this population. However, care needs to be taken to avoid overdiagnosis and overtreatment. Early intervention with medication in young, mild hypertensives (blood pressure, >140/90 mm Hg) free of cardiovascular disease could be considered following a 1-year trial of lifestyle modification. Given the uncertainty in this group of patients, shared decision-making is crucial, involving patients, primary care physicians, and specialists.

**Table 2.** Indications to Refer Young-Onset Hypertension to Secondary Care
Age <30 y with no risk factors
Resistant hypertension
Sudden deterioration in BP control
Evidence of end-organ damage
Clinical features or investigations suggesting a secondary cause of hypertension

**Table 3.** Summary of Recommendations for Young Adults With Hypertension
Public health policy to optimize fetal and early-life health
Lifestyle modifications to improve risk profile including physical activity
BP threshold to consider intervention at 140/90 mm Hg
Arrange ambulatory BP monitoring
Assess for end-organ damage and secondary causes by measuring renal function, thyroid function, microalbuminuria, and ECG
Echocardiogram if abnormal ECG or finding of LVH would alter treatment
Refer selected patients to secondary care for further assessment (Table 2)
If starting drug treatment in women, consider pregnancy potential

**Figure.** Summary of review of young-onset hypertension. ACE indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta blocker; BP, blood pressure; CCB, calcium channel blocker; CT, computed tomography; LVH, left ventricular hypertrophy; MRI, magnetic resonance imaging; RCT, randomized controlled trial; and US, ultrasound.

Sources of Funding

Our group is supported by the British Heart Foundation (FS/18/18/33522, T.C. Hinton; FS/17/38/32935, Z.H. Adams; FS/17/49/32917, K.A. Hope), British Society for Heart Failure (R. Baker), National Institute for Health Research Biomedical Research Centre (A.K. Nightingale), James Tudor Foundation, and the David Telling Charitable Trust. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health and Social Care.

Footnotes

References

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