Life course blood pressure, blood pressure variability and subclinical markers of cardiovascular disease

Background:
Elevated blood pressure (BP) is a key modifiable risk factor for subclinical markers of cardiovascular disease, predisposing individuals to cardiovascular disease. Emerging evidence suggests that BP variability (a measure of fluctuation in BP levels over time) also contributes to cardiovascular risk. However, the clinical importance of within-visit BP variability (BP variability in a single visit) is unclear. Furthermore, although child and adult measures of BP have been independently associated with the subclinical markers of cardiovascular disease, the contribution of BP throughout the life course to subclinical markers of cardiovascular disease is inconclusive. These knowledge gaps are addressed in this thesis across five original research studies that used BP data measured at multiple time-points spanning from infancy to adulthood.
Aims:
Study 1 (Chapter 2) investigated the impact of within-visit BP variability on correct BP classification. Study 2 (Chapter 3) investigated the association between within-visit BP variability and subclinical markers of cardiovascular disease. Study 3 (Chapter 4) assessed the tracking (persistence) of BP from childhood to adulthood. Study 4 (Chapter 5) and study 5 (Chapter 6) determined the relative contribution of BP at different life stages on future subclinical markers of cardiovascular disease characterised by arterial stiffness and intima-media thickness.
Methods:
Studies 1 to 4 used data from participants in the Cardiovascular Risk in Young Finns Study (N =1869 to 3010), in which several measures of seated BP were recorded at up to 9 visits from 1980 (3−18 years) to 2018 (41−58 years) at 3- to 9-year intervals. Within-visit BP variability at each visit was calculated as the BP change between each of three BP readings, as well as the standard deviation of these BP readings measured at each visit. BP classification (hypertension diagnosis) was determined according to established guidelines for children (≥95th age-, sex-, and height specific percentiles) and adults (systolic/diastolic BP ≥140/90 mmHg). Subclinical markers of cardiovascular disease measured in adulthood were arterial stiffness (carotid distensibility, arterial pulse wave velocity), common carotid intima-media thickness, brachial flow-mediated dilation, carotid plaque, coronary artery calcification, and left ventricular mass index. Study 5 used data from participants in the Special Turku Coronary Risk Factor Intervention Project (N = 534), in which seated BP was measured annually from age 7 months to 20 years and again at age 26 years when intima-media thickness was also measured.
Results:
Study 1 found that the individual variability between BP measures within a single clinic visit (within-visit BP variability) significantly influenced correct BP classification (hypertension diagnosis). These findings indicate that the average of several BP readings be used for hypertension diagnosis, rather than relying on one reading as advocated by some guidelines. Study 2 showed that neither within-visit BP variability during childhood, adulthood, or across the observed life course associated with subclinical markers of cardiovascular disease in adulthood. Thus, beyond the findings of study 1, there is limited clinical importance of within-visit BP variability as a marker of subclinical cardiovascular disease. Study 3 showed that BP tracks from childhood to adulthood over 38 years, whereby children with high normal/hypertension had 2.17 times the odds (95 % confidence interval, 1.95, 2.40) for maintaining high normal/hypertension in adulthood. These data indicate that childhood BP significantly relates to BP in later life. Study 4 showed that cumulative exposure to higher levels of BP across the life course from childhood, to young- and mid-adulthood was associated with increased arterial stiffening in mid-adulthood. The highest contribution was attributed to mid-adulthood BP (e.g., relative contribution for pulse wave velocity, childhood: 2.6 %, young adulthood: 5.4 %, mid-adulthood: 92.0 %). Study 5 showed that cumulative exposure to higher BP levels across the early life course from infancy, preschool, childhood, adolescence, and young adulthood was associated with increased carotid intima-media thickness in young-adulthood, with approximately equal contribution from BP at each observed life stage. The data from studies 4 and 5 provide information on the clinical cardiovascular relevance of life course BP, whereby early life BP had sustained and long-lasting contributions to arterial stiffening and carotid intima-media thickening.
Conclusions:
Studies in this thesis provide novel data on the need to use repeated measurements for BP classification. This should be a consistent recommendation of all BP guidelines but is not currently the case. However, the suggestion to consider within-visit BP variability as a cardiovascular risk indicator is not supported by evidence presented in this thesis. Finally, this thesis found that BP levels at all stages across the life course are what really matters to BP-related cardiovascular damage, and this observation should be used in support of efforts to achieve and maintain lower BP from early on in life. Altogether, these findings could lead to improvements in diagnosis and management of hypertension and prevention of BP-related cardiovascular damage.