Department of Mother and Child Health Research, Institute for Clinical Effectiveness and Health Policy (IECS-CONICET), Buenos Aires, Argentina.
Argentine Cochrane Centre, Institute for Clinical Effectiveness and Health Policy (IECS-CONICET), Buenos Aires, Argentina.
Cochrane Database Syst Rev. 2022 Jan 11;1(1):CD010037. doi: 10.1002/14651858.CD010037.pub4.
Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure.
To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension.
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures.
Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence.
The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eight studies; I = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; seven studies ; I = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies; I = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I = 51%, high-certainty evidence, respectively. None of the studies reported adverse events.
AUTHORS' CONCLUSIONS: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.
高血压是一个主要的公共卫生问题，会增加心血管疾病和肾脏疾病的风险。多项研究表明，钙摄入量与血压呈负相关，即使在血压正常范围内的个体中，血压的微小降低也能迅速降低血管疾病的风险。这是对评估钙补充剂作为预防保健措施对正常血压人群降压效果的首次更新。
评估钙补充剂与安慰剂或对照相比，在正常血压人群中降低血压和预防原发性高血压的疗效和安全性。
Cochrane 高血压信息专家检索了截至 2020 年 9 月的随机对照试验数据库：Cochrane 高血压专业登记册、CENTRAL（2020 年，第 9 期）、Ovid MEDLINE、Ovid Embase、世界卫生组织国际临床试验注册平台和美国国立卫生研究院正在进行的试验登记册，ClinicalTrials.gov。我们还就进一步发表和未发表的工作联系了相关论文的作者。检索没有语言限制。
我们选择了将正常血压人群随机分配到膳食钙干预（如补充或食物强化）与安慰剂或对照的试验。我们排除了准随机设计。主要结局是高血压（定义为血压≥140/90mmHg）和血压测量。
两名综述作者独立选择纳入的试验，提取数据并评估偏倚风险。我们使用 GRADE 方法评估证据的确定性。
2020 年更新的搜索确定了四项新的试验。我们共纳入了 20 项试验，共有 3512 名参与者，但只有 18 项研究纳入了 3140 名参与者的荟萃分析。没有一项研究报告高血压为二分类结局。对收缩压和舒张压的影响为：平均差值（MD）-1.37mmHg，95%置信区间（CI）-2.08，-0.66；3140 名参与者；18 项研究；I=0%，高确定性证据；MD-1.45，95%置信区间（CI）-2.23，-0.67；3039 名参与者；17 项研究；I=45%，高确定性证据。对年龄小于 35 岁的人收缩压和舒张压的影响为：MD-1.86，95%置信区间（CI）-3.45，-0.27；452 名参与者；8 项研究；I=19%，中等确定性证据；MD-2.50，95%置信区间（CI）-4.22，-0.79；351 名参与者；7 项研究；I=54%，中等确定性证据。对年龄在 35 岁或以上的人收缩压和舒张压的影响为：MD-0.97，95%置信区间（CI）-1.83，-0.10；2688 名参与者；10 项研究；I=0%，高确定性证据；MD-0.59，95%置信区间（CI）-1.13，-0.06；2688 名参与者；10 项研究；I=0%，高确定性证据。对女性收缩压和舒张压的影响为：MD-1.25，95%置信区间（CI）-2.53，0.03；1915 名参与者；8 项研究；I=0%，高确定性证据；MD-1.04，95%置信区间（CI）-1.86，-0.22；1915 名参与者；8 项研究；I=4%，高确定性证据。对男性收缩压和舒张压的影响为 MD-2.14，95%置信区间（CI）-3.71，-0.59；507 名参与者；5 项研究；I=8%，中等确定性证据；MD-1.99，95%置信区间（CI）-3.25，-0.74；507 名参与者；5 项研究；I=41%，中等确定性证据。无论基线钙摄入量如何，两性的效果都是一致的。对收缩压的影响为：MD-0.02，95%置信区间（CI）-2.23，2.20；302 名参与者；3 项研究；I=0%，剂量小于 1000mg 时的中等确定性证据；MD-1.05，95%置信区间（CI）-1.91，-0.19；2488 名参与者；9 项研究；I=0%，剂量为 1000 至 1500mg 时的高确定性证据；MD-2.79，95%置信区间（CI）-4.71，0.86；350 名参与者；7 项研究；I=0%，剂量大于 1500mg 时的中等确定性证据。对舒张压的影响为：MD-0.41，95%置信区间（CI）-2.07，1.25；201 名参与者；2 项研究；I=0，中等确定性证据；MD-2.03，95%置信区间（CI）-3.44，-0.62；1017 名参与者；8 项研究；和 MD-1.35，95%置信区间（CI）-2.75，-0.05；1821 名参与者；8 项研究；I=51%，高确定性证据。没有研究报告不良事件。
增加钙摄入量可轻微降低正常血压人群的收缩压和舒张压，特别是在年轻人中，这表明钙可能在预防高血压中发挥作用。多项预先指定的亚组分析和可能的剂量反应效应进一步证实了这一结论。即使血压降低幅度很小，也可能对降低血管疾病风险有重要的健康意义。收缩压降低 2mmHg 预计可使中风死亡率降低约 10%，缺血性心脏病死亡率降低约 7%。非常需要针对年轻人进行足够规模的临床试验。亚组分析应包括基础钙摄入量、年龄、性别、基础血压和体重指数。我们还需要评估副作用、最佳剂量和改善钙摄入的最佳策略。
