Findings in this paper demonstrated that education was inversely associated with longitudinal trajectories of mean SBP in females and males. Furthermore, especially in females, lower education was associated with higher post-baseline SBP even among the participants with the same baseline SBP. This suggests that low education may have a long-term impact on changes over time in blood pressure in females. Adjusting for the time-varying values of conventional risk factors, measured at the same time as the blood pressure, typically reduced the strength of these associations. Associations of education with DBP were generally weaker than with SBP, for both females and males.
Few studies have investigated sex-specific longitudinal trajectories of blood pressure, particularly over a substantial proportion of the life course. Diez Roux et al. in the ARIC cohort (n = 8555) aged 45 to 64 years at baseline and followed using 4 examinations over a period of 9 years, found in white participants, that education was marginally inversely associated with increases in blood pressure after adjusting for age, sex, center, medication use, and reported interactions between time and sex, and interactions between time and baseline age . The 5-year change in mean SBP was 6.0 mmHg for those with <high school degree and 5.3 mmHg for those with a college degree. Further adjustment for baseline SBP somewhat reduced the association strength, to 5.9 mmHg for <high school and 5.5 mmHg for participants with college degree. Associations were weaker in black participants. Strand et al. demonstrated, in a large prospective study of 48,422 males and females aged 35-49 followed for 14 years using three examinations, that education was inversely associated with increases over time in SBP in males and females, after adjusting for year of birth ; socioeconomic disparities widened over time in females but not males. In a study on the Framingham Offspring cohort that included only participants aged 20-29 years at baseline (many of whom may not have completed education yet), education was not significantly associated with mean 8-year change in SBP or DBP in males or females, after adjusting for age . In the CARDIA study of 2913 participants aged 18-30 years at baseline education was significantly inversely associated with mean 15-year change in both SBP and DBP . Specifically for SBP, those with <high school degree had a 15-year mean increase of 8.2 mmHg versus only 0.7 mmHg for participants with >college graduate degree. However the observed associations were not adjusted for covariates . Although prior cross-sectional studies suggested that associations may be stronger in females than males , little is known about sex-specific associations between education and blood pressure trajectories, particularly over long periods of the life course (>20 years follow-up). Finally, little is known about the effects of adjusting for use of antihypertensive medications, body mass index, alcohol consumption, smoking or other potential mechanisms that may, at least partly, mediate the impact of lower education on longitudinal trajectories of blood pressure. This study added to the literature sex-specific information demonstrating that education is inversely associated with longitudinal trajectories of mean SBP in females and males over a substantial proportion of the life course (approximately 30 years) and that association may be stronger in females than males. Furthermore, in females, lower education was associated with a higher mean post-baseline SBP even among participants with the same baseline SBP, suggesting a possible long-term impact of lower education. Adjusting for up-dated values of conventional risk factors typically reduced strengths of association, but in females the impact of lower education remained statistically significant. For DBP, association strengths were generally weaker for both females and males.
The primary candidate mechanisms by which education may influence longitudinal trajectories of blood pressure involve conventional risk factors for hypertension, including smoking, obesity, blood pressure medication use, and alcohol consumption. In this study, in females, education was inversely associated with anti-hypertensive medication use, body mass index and smoking, and directly associated with alcohol consumption. In males, education was inversely associated with body mass index, alcohol consumption and smoking, and not associated with antihypertensive use. Furthermore, the estimated effects of education tended to somewhat decrease after adjusting for these potential mechanisms (particularly in males), suggesting that they may be at least partial explanatory pathways for the observed association between educational attainment and longitudinal trajectories of blood pressure. It is important to note that biases can be induced by adjusting for variables that may partly mediate the effect of exposure; therefore, these mechanistic findings should be interpreted with caution . Furthermore, there remain plausible confounders unadjusted for, such as childhood socioeconomic circumstances (which are associated with adulthood education and blood pressure ), parental blood pressure (which may be associated with offspring education and has been related to offspring blood pressure ), intelligence (which is associated with educational attainment and CHD risk ), and early life obesity (that could affect upward social mobility via obesity discrimination particularly in women [18, 19], and is related to blood pressure in adulthood . Consequently, residual confounding remains a possibility.
Low educational attainment has been demonstrated to predispose individuals to high strain jobs, characterized by high levels of demand and low levels of control, which have been associated with elevated blood pressure [21, 22]. Other related mechanisms involve stress-induced sympathetic nervous system activation due to stressful conditions outside of work, that are also associated with low educational attainment. These may be particularly important for women. It has been shown that women with low education have higher risk of co-occurring psychosocial determinants of poor health, including single-parenting, depression, income below the poverty threshold, and unemployment, compared to men with low education . Consequently, low socioeconomic position may be a stronger determinant of hypertension risk in women compared with men. This may be one of the explanations for why we found a significant interaction between sex and education, and somewhat stronger associations between education and blood pressure in women than men. The extent of health care available for people of low socioeconomic position is typically less than what is available for those with high socioeconomic position, hence limiting access to treatments of hypertension . Furthermore, there is evidence that people of low socioeconomic position have less healthful diets, such as lower rates of fruit and vegetable consumption, and higher salt intake, which may be additional mechanisms contributing to disparities in blood pressure [25, 26].
It has been demonstrated that although both SBP and DBP are positively associated with incidence of coronary heart disease, there are differences in the way SBP and DBP evolve over the life course. SBP tends to increase steadily with age, while DBP tends to increase until age 50 years, and to decrease steadily after that age [4, 8, 27]. The mechanisms responsible for the age-related increase in DBP among younger people likely involve an atherosclerotic increase in peripheral resistance, caused by narrowing of the smaller arteries and arterioles [8, 28]. In contrast, for older individuals, structural damage and calcification due to arteriosclerosis in the larger conduit arteries can result in loss of arterial compliance, which can cause a rise in SBP, but a reduction in DBP [8, 28]. As the burden of hypertension is greatest after the age of 50 years, and it is exceedingly uncommon to have diastolic hypertension without concurrent systolic hypertension in adults over the age of 50 years, it has been argued that SBP is by far the more important measure of the two in terms of predictive importance for population health .
Studies generally show consistent inverse associations between educational attainment and longitudinal changes in SBP [4, 6, 7], with the exception of young participants aged 20-29 years at baseline, followed over 8 years in the study by Hubert et al.  However, findings are less consistent for DBP, where studies have shown inverse , null , or even positive  associations between educational attainment and longitudinal changes in DBP. Our findings demonstrated fairly robust inverse associations of education with SBP, and weaker inconsistent associations with DBP. The pathophysiological mechanisms (e.g. smoking, obesity, alcohol consumption) that cause steady increases over the life course for SBP but not DBP, and also tend to be inversely associated with socioeconomic position, may explain the more consistent findings for the inverse association between education and changes in SBP rather than DBP over the life course. However, adjustment for these variables in our study appeared to account for only a small amount of the association in females, and a larger amount of the (weaker) association in males, suggesting there may be other explanatory factors, particularly in females.
Strengths and Weaknesses
Strengths of this study include having access to data on approximately 30 years of longitudinal blood pressure measurements. Furthermore, follow-up rates of the Framingham Heart Study are considered to be high for observational studies, decreasing risk of bias due to loss-to-follow-up. Finally, measurements of blood pressure were performed using methods and equipment providing good accuracy and precision, and analyses relied on statistical methods appropriate for longitudinal repeated-measures studies.
With regard to weaknesses, because the historical design of the Framingham Offspring Study reflected the population of Framingham, Massachusetts at study onset in 1948, the Original and Offspring cohorts are largely composed of white participants. Consequently, the generalizability of our findings to other races/ethnicities is uncertain. Furthermore, although we had up to 7 measurements for each covariate, we expect there to be reasonable residual confounding due to imperfect measurement of obesity (body mass index), and self-reported alcohol consumption, smoking and antihypertensive medication use.