In this issue of the Journal, Gray et al. (1) present evidence that blood pressure matters, not just during middle age and beyond, but also early in life when the short-term risk of clinical cardiovascular events is very low. Using blood pressure measurements from well over one-half century ago (1914 to 1952) on thousands of male students entering Harvard University (mean age 18 years), the authors demonstrate that blood pressure during young adulthood is associated with death from heart disease, cardiovascular disease, and all causes decades later. Other studies have found similar associations between young adult blood pressure and long-term mortality (2- 6); this analysis is unique because a measurement of blood pressure (self-reported hypertension) during middle age was also available. Even after adjusting for this factor, blood pressure early in life was a very strong predictor of mortality later in life.

The primary weakness of this analysis is that the key measurement used to rule out mediation by blood pressure later in life is from a mailed questionnaire. Administered once in either 1962 or 1966, the questionnaire asked whether a physician had previously diagnosed the participant with hypertension. This measure of middle-age blood pressure is inherently limited, both because of its dichotomous nature and because of the measurement errors in participant self-report. Additionally, the threshold for defining hypertension was higher at the time of this assessment (e.g., systolic blood pressure >160 mm Hg). Thus, even if participants were completely accurate in self-reporting the absence of a prior hypertension diagnosis, their systolic blood pressure could reasonably be expected to vary across a wide range of values, anywhere from 115 to 155 mm Hg. Because this simple 1-time self-report of hypertension does not capture the true full range of blood pressure variation in the population, the analysis cannot fully account for mediation by later-life blood pressure exposure.

When evaluated in the context of prior studies, however, it seems likely that the primary hypothesis (that blood pressure matters during young adulthood) is correct. Many studies have shown associations between blood pressure measured early in life and cardiovascular pathology, as measured by autopsy (7- 8), echocardiogram (9), carotid ultrasound (10- 11), endothelial dysfunction (12), and coronary calcification (13). Our prior analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) study estimated cumulative exposure to elevated blood pressure during young adulthood (age 20 to 35 years), focusing on pre-hypertension–range elevation, and found associations with coronary calcium at ages 35 to 50 years that were not explained by later-life blood pressure at the time of coronary calcium assessment (14). Although we could not measure clinical events or mortality, we did have multiple repeated measures of blood pressure throughout the 20-year follow-up period and were able to adjust very carefully for middle-age blood pressure exposure and show that the association with early-life blood pressure was not explained by later-life exposure. These complementary studies help bolster the inference that blood pressure during young adulthood causes vascular damage that results in clinical events and mortality later in life.

The clinical implications of this inference are potentially profound. Despite adult hypertension guidelines that recommend treatment of hypertension regardless of age (15), young adults with hypertension are less likely than older age groups to be aware of their hypertension, to be on treatment, and to have their hypertension adequately controlled (16). Although improvements have been made across all of these parameters over time, improvements have consistently lagged in young adults. Several factors may contribute to undertreatment of hypertension in this age group. Young adults are likely to lack health insurance, to lack a usual source of care, and to interact with the medical system only for episodic care (17). Physicians caring for young adults may be reluctant to label them with a medical diagnosis that may have implications for future insurance, jobs, and perceptions of health. Physicians may also have concerns about treating a risk factor such as hypertension when the benefits of such treatments may be several decades in the future and the long-term safety of medical treatment may be questioned. Although these concerns are not easily dismissed, the reality of the growing national burden of hypertension remains. For young adults and the physicians and healthcare systems that care for them, the difficult challenge of optimizing blood pressure in young men and women in their 20s and 30s is likely to grow more difficult with rising rates of obesity (18- 19). Optimizing blood pressure in young African Americans is a particularly difficult and important challenge: blood pressure elevations in African Americans are more likely to begin earlier in life (20), and the spectrum of hypertensive-related morbidity occurs at younger ages, contributing importantly to premature morbidity and mortality and associated health disparities (21- 22).

The message of Gray et al. (1) poses new challenges for all of us, regardless of our perspective on this issue. Researchers must address the difficult evidence gap in the lack of randomized controlled trials of blood pressure treatment in young adults and the most effective and efficient approach for generating and evaluating evidence of treatment effect on long-term outcomes in this population. Clinicians and public health practitioners must address the growing need to emphasize and support lifestyle approaches to the prevention and control of hypertension, including a healthy diet and avoidance of excessive weight gain, that remain the cornerstone of prevention in a young adult population. Harvard students started having their blood pressure measured for this study in 1914. Now, nearly a century later, their message about the importance of blood pressure in young adults has been received, and despite the transmission delay, it is a message with more public health relevance than ever.