Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
J Hypertens. 2022 Mar 1;40(3):615-623. doi: 10.1097/HJH.0000000000003057.
Although peak aortic flow (Q) is now recognized as a major determinant of hypertension in Africa, current therapy has no proven ability to target this change. The mechanisms of this effect, therefore, require elucidation. We compared the intrafamilial aggregation and heritability of Q to that of the vascular determinants of pulse pressure (PP) and SBP in Africa.
The intrafamilial aggregation and heritability of Q and aortic characteristic impedance (Zc) or total arterial compliance (TAC) was determined in 669 participants of 194 families (69 father-mother, 385 parent-child, 157 sibling-sibling pairs) in a community in Africa with prevalent flow-dependent primary hypertension. Haemodynamics were determined from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures.
No mother-father correlations were noted for either Q or Zc. However, with adjustments for confounders, parent-child (P < 0.0001) and sibling-sibling (P < 0.0001) correlations were noted for Q. Parent-child and/or sibling-sibling correlations were also noted for Zc or TAC but were weaker for Zc and mother-father correlations were noted for TAC. Moreover, Q showed markedly stronger multivariate adjusted heritability estimates (h2 = 0.82 ± 0.07, P < 0.0001) than Zc (h2 = 0.44 ± 0.10, P < 0.0001)(P < 0.005 for comparisons) and TAC (h2 = 0.47 ± 0.08, P < 0.0001)(P < 0.005 for comparisons). Importantly, the heritability of Q was also greater than that for PP (h2 = 0.12 ± 0.09, P = 0.11) (P < 0.0001 for comparisons), or SBP (h2 = 0.13 ± 0.10, P = 0.08) (P < 0.0001 for comparisons).
Of the haemodynamic determinants of SBP, peak aortic flow is the most strongly inherited in Africa. Peak aortic flow, therefore, represents an important target for identifying novel therapeutic approaches to controlling SBP in Africa.
尽管峰值主动脉流量(Q)现在被认为是非洲高血压的主要决定因素,但目前的治疗方法并没有证明能够针对这种变化。因此,需要阐明这种效应的机制。我们比较了 Q 与脉压(PP)和 SBP 的血管决定因素在非洲的家族内聚集和遗传性。
在非洲一个社区中,对 194 个家庭(69 个父母-子女、385 个亲子、157 个兄弟姐妹)的 669 名参与者进行了 Q 和主动脉特征阻抗(Zc)或总动脉顺应性(TAC)的家族内聚集和遗传性的测定。血流依赖性原发性高血压患者的心脏输出道(超声心动图)和中心动脉压力的速度和直径测量来确定血流动力学。
无论是 Q 还是 Zc,都没有发现母亲-父亲之间的相关性。然而,在调整了混杂因素后,发现了亲子(P<0.0001)和兄弟姐妹(P<0.0001)之间的 Q 相关性。也注意到了 Zc 或 TAC 的亲子或兄弟姐妹相关性,但 Zc 的相关性较弱,并且 TAC 存在母亲-父亲相关性。此外,Q 显示出明显更强的多变量调整遗传力估计值(h2=0.82±0.07,P<0.0001),而 Zc(h2=0.44±0.10,P<0.0001)(比较时 P<0.005)和 TAC(h2=0.47±0.08,P<0.0001)(比较时 P<0.005)。重要的是,Q 的遗传力也大于 PP(h2=0.12±0.09,P=0.11)(比较时 P<0.0001)或 SBP(h2=0.13±0.10,P=0.08)(比较时 P<0.0001)。
在 SBP 的血流动力学决定因素中,峰值主动脉流量在非洲的遗传性最强。因此,峰值主动脉流量是确定控制非洲 SBP 的新治疗方法的重要靶点。