Staessen J A, Roels H, Lauwerys R R, Amery A
Department of Molecular and Cardiovascular Research, Katholieke Universiteit te Leuven, Belgium.
J Hum Hypertens. 1995 May;9(5):303-28.
The possible association between low-level lead exposure and blood pressure (BP) remains debated. The purpose of this review was: (1) to determine whether the available studies in humans support a positive association, in particular at lower exposure levels (blood lead concentration < 1 mumol/l), and (2) to explore whether animal studies and the proposed pathophysiological mechanisms are supportive of a positive and causal association between lead exposure and hypertension. A meta-analysis of 23 studies included 33,141 subjects recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results had been adjusted for age, and most studies also considered additional confounders. The association between BP and blood lead was similar in both sexes. In all 23 studies combined, a two-fold increase in blood lead concentration was associated with a 1 mm Hg rise in the systolic pressure (CI 0.4-1.6 mm Hg; P = 0.002) and with a 0.6 mm Hg increase in the diastolic pressure (CI 0.2-1.0 mm Hg; P = 0.02). Of 21 animal studies, one was carried out in dogs, one in pigeons and the remainder in various rat strains. In 15 studies, in which the lead dose in drinking water or food exceeded 1 p.p.m. the association between BP and exposure was found to be positive in seven, inconsistent in three, absent in four and negative in one. Of the six studies at lower exposure levels (< or = 1 p.p.m.), five found a pressor effect attributable to lead. Whether the lead doses in the animal studies are equivalent to the human exposure levels and to what extent one can extrapolate from genetically heterogeneous animals to humans, remains doubtful. If a causal relation between lead exposure and hypertension exists, the proposed mechanisms may include interference of lead with ion transport across cell membranes, interactions with calcium homeostasis and calcium-mediated processes, direct vasomotor actions and the potentiation of sympathetic stimulation. Interference of lead with the balance between the renin-angiotensin-aldosterone and the kallikrein-kinin systems and impairment of renal function are unlikely to be implicated. On balance, the published evidence suggests that there can only be a weak positive association between BP and lead exposure. The latter relation, which is barely visible at the horizon of epidemiological observation, may not be causal in nature and is unlikely to entail any public health implication in terms of hypertension-related complications.
低水平铅暴露与血压（BP）之间可能存在的关联仍存在争议。本综述的目的是：（1）确定现有的人体研究是否支持存在正相关，尤其是在较低暴露水平（血铅浓度<1微摩尔/升）时；（2）探讨动物研究以及所提出的病理生理机制是否支持铅暴露与高血压之间存在正相关及因果关系。对23项研究进行的荟萃分析纳入了13项调查中从普通人群招募的33141名受试者以及10项研究中的职业群体受试者。除4项研究外，所有研究结果均针对年龄进行了调整，且大多数研究还考虑了其他混杂因素。血压与血铅之间的关联在两性中相似。在所有23项研究综合来看，血铅浓度增加两倍与收缩压升高1毫米汞柱相关（可信区间为0.4 - 1.6毫米汞柱；P = 0.002），与舒张压升高0.6毫米汞柱相关（可信区间为0.2 - 1.0毫米汞柱；P = 0.02）。在21项动物研究中，1项在狗身上进行，1项在鸽子身上进行，其余在各种大鼠品系中进行。在15项研究中，饮用水或食物中的铅剂量超过百万分之一，其中7项研究发现血压与暴露之间存在正相关，3项不一致，4项无关联，1项为负相关。在6项较低暴露水平（≤百万分之一）的研究中，5项发现铅具有升压作用。动物研究中的铅剂量是否等同于人体暴露水平以及能在多大程度上从基因异质性动物外推至人类，仍存在疑问。如果铅暴露与高血压之间存在因果关系，所提出的机制可能包括铅干扰离子跨细胞膜转运、与钙稳态及钙介导过程相互作用、直接的血管舒缩作用以及增强交感神经刺激。铅干扰肾素 - 血管紧张素 - 醛固酮系统与激肽释放酶 - 激肽系统之间的平衡以及损害肾功能的可能性不大。总体而言，已发表的证据表明血压与铅暴露之间可能仅存在微弱的正相关。后一种关系在流行病学观察中几乎难以察觉，可能并非因果关系，就高血压相关并发症而言，不太可能产生任何公共卫生影响。
