Independent association of systolic and diastolic hypertension with CV outcomes
Effect of Systolic and Diastolic Blood Pressure on Cardiovascular OutcomesLiterature - Flint AC, Conell C, Ren X, et al. - N Engl J Med 2019;381:243-51. doi: 10.1056/NEJMoa1803180
Introduction and methods
Focus has been on systolic hypertension after the Framingham Heart Study and other studies demonstrated that systolic hypertension is more important as a predictor of CV outcomes . This was reflected in the 2000 clinical advisory statement from the National High Blood Pressure Education Program  and the American College of Cardiology (ACC)–American Heart Association (AHA) risk estimation tool  does not include diastolic blood pressure (DBP) for determination of CV risk. In contrast to this, clinicians still record and target values for both systolic BP (SBP) and DBP.
The threshold to define hypertension in the 2017 US hypertension guidelines has changed to 130/80 mm Hg , whereas in the European guidelines the threshold is still 140/90 mmHg. Lower targets in the new US hypertension guidelines might result in more patients with diastolic hypotension [6,7,9,10], which might be of concern due to a possible J-curve relationship between DBP and adverse outcomes [5-9].
This study examined whether SBP and DBP were independently associated with the risk of adverse CV outcomes. In addition, the effect of the threshold for the definition of hypertension on the association between SBP and DBP with outcomes was assessed, and a possible J-curve relationship between DBP and outcomes was explored.
A retrospective cohort study was conducted analyzing data from outpatients from Kaiser Permanente Northern California (KPNC), a large integrated health care system . During a 2-year baseline period, initial BP measurements and coexisting conditions were recorded and over an 8-year observation period, additional BP measurements were performed and occurence of MI, ischemic stroke or hemorrhagic stroke was documented. A total of 1.3 million study participants were enrolled, who were ≥18 years and had one BP measurement at baseline (Jan 2007-Dec 2008) and ≥2 BP-measurements during the observation period (Jan 2009-Dec 2016). BP was measured using an automated oscillometric BP cuff.
To determine average hypertension burdens above the thresholds defining hypertension (≥140/90 mmHg or ≥130/80 mmHg), measures were zeroed at the threshold for values at or below the threshold and values above the threshold were expressed in mmHg. Therefore, hypertension burdens were continuous variables with zero values for normal or low BP, and values were standardized to z scores (± SDs from the mean).
- Median number of BP measurements per participant was 22 (IQR: 13-36).
- Applying the 140/90 mmHg threshold resulted in 18.9% of participants with hypertension, and for 130/80 mmHg this was 43.5%.
- Relationship between DBP and composite outcome showed a J-shaped curve, with increased risk in both lowest and highest deciles for DBP. Compared to middle two quartiles, HR for those in the lowest quartile of DBP was 1.44 (95%CI:1.41-1.48), after full adjustment HR was 0.90 (95CI:0.88-0.92) and after adjustment without control for age HR was 1.15 (95%CI:1.13-1.18), indicating that age partially explained the relationship.
- Burden of systolic hypertension (≥ 140 mm Hg) was associated with increased risk of composite outcome (HR per unit increase in z score: 1.18, 95%CI:1.17-1.18, P<0.001). Burden of diastolic hypertension (≥ 90 mmHg) was also independently associated with composite outcome (HR per unit increase in z score: 1.06; 95%CI:1.06-1.07, P<0.001).
- Similar results were shown with thresholds of 130/80 mmHg. For SBP ≥130 mmHg, HR per unit increase in z score was 1.18 (95%CI:1.17-1.19, P<0.001, and for DBP ≥80 mmHg, HR was 1.08, 95%CI:1.06-1.09, P<0.001).
- In participants with SBP <140 mmHg, diastolic hypertension burden >90 mmHg was associated with increased risk for composite outcome (HR per unit increase in z score: 1.66, 95%CI:1.53-1.79, P<0.001) and also in those with SBP <130 mmHg, diastolic hypertension burden >80 mmHg was associated with adverse outcomes (HR per unit increase in z score: 1.52, 95%CI: 1.03-2.23, P=0.03).
- Systolic hypertension ≥140 mm Hg had a greater effect on adverse outcomes in those in the lowest quartile of DBP (HR per unit increase in z score: 1.21, 95%CI:1.20-1.23, P<0.001) than in those in the highest quartile of DBP (HR: 1.16, 95%CI:1.15-1.17, P<0.001). Similar results were observed when a threshold for defining systolic hypertension of ≥ 130 mm Hg was used.
This large retrospective cohort study including people from Northern California demonstrated that both systolic and diastolic hypertension were associated with increased risk for adverse CV outcomes. The association was similar when using threshold defining hypertension as ≥140/90 mmHg or ≥130/80 mmHg. A J-curve relationship between DBP and outcomes was seen, with higher risk in those with lowest and highest DBP values. The higher risk of outcomes in those with lower DBP could partially be explained by age, other covariates and by a greater effect of systolic hypertension.