High BP in Young Adults a Harbinger of Premature CVD, Death

Damian McNamara

November 13, 2018

Young adults with hypertension have a significantly elevated risk for subsequent cardiovascular events and all-cause mortality in middle age compared to their normotensive counterparts, results of a large prospective study show.

"Our study is among the first to report that high blood pressure poses risk of heart and stroke events for people under age 40," principal investigator Yuichiro Yano, MD, PhD, of the Department of Community and Family Medicine at Duke University School of Medicine in Durham, North Carolina, told Medscape Medical News.

The study was published online November 6 in JAMA.

New Hypertension Guidelines

In 2017, the American College of Cardiology/American Heart Association released new hypertension guidelines.

The new recommendations lowered the blood pressure (BP) thresholds for hypertension from ≥140/90 mmHg to ≥130/80 mmHg.

"The change increased the prevalence of hypertension twofold to threefold among young adults," Yano said.

However, no previous research had shown that hypertension, as defined by the new criteria, is something that younger people sh ould be concerned about as a potential precursor to serious problems, he said.

For instance, in the Build and Blood Pressure Study, a systolic BP >115 mmHg and a diastolic BP >75 mmHg were associated with an increased mortality risk.

In addition, results from the Multiple Risk Factor Intervention Trial (MRFIT) indicated that the cardiovascular disease (CVD) event rate increased with higher BP in men aged 35 to 44 years.

However, these prior studies only measured BP on a single occasion, which "might not fully reflect a person's BP phenotype in young adulthood," the current investigators note.

To determine whether young adults who developed hypertension as defined by the new BP guideline before age 40 have a higher risk for CVD events compared to their counterparts who maintain normal BP, the investigators analyzed data from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study.

Long-term Follow-up

CARDIA began in March 1985 and included 5115 African American and white participants aged 18 to 30 years from four US centers. Outcomes through August 2015 were available.

In contrast, Yano and colleagues classified BP using measurements from at least two clinic visits (mean, 5.0 visits; SD, 1.1) over a median of 10.7 years.

Baseline examinations were conducted in 1985 and 1986 with follow-up assessments at regular intervals up to 30 years later.

During examinations in the first 15 years, trained research staff measured right arm brachial artery BP three times at 1-min intervals. They recorded the mean of the second and third measurements.

Perhaps not surprisingly, for participants who were initially classified as having stage 1 and 2 hypertension using the 2017 ACC/AHA criteria, BMI levels were higher, education levels were lower, glucose and total cholesterol levels were higher, and HDL cholesterol levels were lower compared with the normal BP group.

In addition, participants whose BP was elevated to degree before age 40 were older, more likely to be men, and more likely to be African American compared to participants whose BP was normal.

The final analytic sample included 4851 participants. The mean age at follow-up was 35.7 years; 2657 participants were women (55%), and 2441 were African Americans (50%). A total of 206 individuals (4%) were taking antihypertensive medication when follow-up assessments began.

A total of 2574 participants had normal BP. Another 445 met the new criteria for elevated BP; 1194 met criteria for stage 1 hypertension, and the remaining 638 had stage 2 hypertension.

The investigators also collected data on hospitalizations and outpatient medical procedures. They confirmed any reported hospital admissions or outpatient visits and adjudicated CVD events using medical records.

The study's primary outcome of composite CVD events included fatal and nonfatal coronary heart disease, hospitalization for heart failure, stroke, transient ischemic attack, or an intervention for peripheral artery disease. Events up to August 2015 were included in the study.

Key Outcomes

A total 228 CVD events occurred during a median 19 years of follow-up. There were 109 coronary heart disease events, 63 strokes, and 48 cases of heart failure; eight participants developed peripheral artery disease, and 319 participants died from any cause.

All CVD events and deaths occurred before participants turned 60 years of age.

Table 1. CVD Events by BP Class*

  CVD Event Rate 95% Confidence Interval
Normal BP 1.37 1.07 - 1.75
Elevated BP 2.74 1.78 - 4.20
Stage 1 hypertension 3.15 2.47 - 4.02
Stage 2 hypertension 8.04 6.45 - 10.03
*CVD event rate per 1000-person years.


Similar to the reported CVD event rates, mortality rates per 1000 person-years increased sequentially from the normotensive to the most hypertensive group.

The mortality rate was 2.89 in the normal BP cohort (95% CI, 2.44 - 3.42); 3.22 in the elevated BP group (95% CI, 2.18 - 4.77); 3.67 in the stage 1 hypertensive cohort (95% CI, 2.93 - 4.60); and 7.96 in the stage 2 hypertensive group (95% CI, 6.41 - 9.89).

Compared to the normal BP group, patients classified as having stage 2 hypertension were at significantly higher risk for all-cause mortality (HR, 2.82; 95% CI, 2.14 - 3.71) in an unadjusted model. The significant association remained after adjusting for covariates.

In contrast, participants in the elevated BP and stage 1 hypertensive group were not at a significantly higher risk for death compared to those with normal BP.

Interestingly, the researchers found no significant interaction between BP and race or sex in association with CVD events or all-cause mortality (for all, P > .10).

The CVD rates were significantly higher in the hypertensive vs normotensive participants in both unadjusted and adjusted analyses.

Table 2. CVD Event Rates Compared to Normotensive Participants*

Unadjusted Analysis Hazard Ratio 95% Confidence Interval
Elevated BP 2.01 1.22 - 3.28
Stage 1 hypertension 2.31 1.63 - 3.27
Stage 2 hypertension 6.03 4.33 - 8.40
Adjusted Analysis  
Elevated BP 1.67 1.01 - 2.77
Stage 1 hypertension 1.75 1.22 - 2.53
Stage 2 hypertension 3.49 2.42 - 5.05
*A multivariable analysis controlled for age, sex, race, study site and education level.

Early Identification

Yano is a proponent of the 2017 ACC/AHA guidelines for this population. The BP classification system "could help identify young adults at higher risk for heart or stroke events," he said.

Once any adult is diagnosed with elevated BP or hypertension, he said, experts recommend nonpharmacologic interventions, the most important being weight loss, reducing sodium consumption, and consuming a healthy diet. He added that a diet consisting of fruits, vegetables, whole grains, and low-fat dairy products, with reduced content of saturated and total fat, is recommended.

Pharmacologic treatment for which the benefit-to-harm ratios over a lifetime are unclear may be impractical for young adults, the researchers note.

In contrast, for young adults who are at high CVD risk and have a history of diabetes, chronic kidney disease, or CVD, pharmacologic interventions are recommended, Yano said. If onset of hypertension occurs before age 30, a screen for secondary hypertension is warranted.

In the future, the researchers would like to evaluate the optimal approach to antihypertensive therapy for young adults with hypertension.

Questions remain regarding the timing of treatment, the effectiveness of low-dose antihypertensive agents, and what the optimal BP goal should be in this younger population.

"We are thinking that clinical trials are needed to determine if pharmacological treatments benefit can be achieved in young adults with elevated blood pressure or hypertension who do not have a history of diabetes, chronic kidney disease, or cardiovascular disease," Yano said.

Causality Not Established

In an accompanying editorial, Ramachandran S. Vasan, MD, of the Section of Preventive Medicine and Epidemiology in the Department of Medicine at Boston University School of Medicine, notes that the investigators found a stepwise increase in the multivariable adjusted CVD risk across increasing blood pressure categories compared with normal blood pressure "with notable consistency in sensitivity analyses using blood pressure measures at more than one time-point, across individual CVD end points evaluated and across race groups."

He notes that BP was normal for a majority of young adults in the study. In addition, those in a higher BP category often had comorbid CVD risk factors, such as greater BMI, increased fasting glucose levels, and more smoking. This finding demonstrates "that these risk factors cluster, thereby increasing CVD risk synergistically."

He points out that the absolute CVD event rates were low, a finding consistent with the age of the study population. He also notes that "the observation of an elevated risk of premature CVD risk in young adults does not establish causality nor does it necessarily imply that intervention to lower blood pressure in this age group will mitigate CVD risk."

The CARDIA study was supported by the National Heart, Lung and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, the Kaiser Foundation Research Institute, Johns Hopkins University School of Medicine, the National Institute of General Medical Sciences of the National Institute of Health, the American Heart Association, and by the Intramural Research Program of the National Institute on Aging. Dr Yano and Dr Vasan have disclosed no relevant financial relationships.

JAMA. Published online November 6, 2018. Abstract, Editorial

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