The relationship between potassium and magnesium status and health outcomes: mortality and neurological performance

腦中風為重大傷病，會導致死亡及神經功能受損，日常活動甚至是生活品質都會因為神經功能缺損而受到影響。礦物質營養素，鉀、鎂在腦中風以及其兩大危險因子，高血壓和糖尿病之致病機轉中均扮演重要角色。飲食當中攝取過多的鈉會使血壓上升及增加中風的風險，鉀的補充具有降低血壓及中風風險的作用，鎂的缺乏和糖尿病發生率成顯著相關，在中風初期投予鎂是否有長期神經保護的作用，也是當前熱門的議題。然而以長期維持營養的概念管理高危險人群，如：老人與中風患者之鉀鎂營養狀況以改善其預後，尚缺乏深入之研究。 研究一、血鉀和老人死亡率的相關性（前瞻性世代研究） 背景/目的：已有研究報告指出血鉀濃度和已存在心血管疾病和腎功能受損 (pre-existing cardiovascular disease and impaired renal function) 的病人的不良事件呈負相關，但在社區老人 (community-based elderly individuals)，血鉀正常範圍值是否太寬和其不良事件的關係尚未被詳細研究。目的：本研究針對社區老人來檢驗低和高正常血鉀值 (low- and high-normal serum potassium) 和心血管疾病及全死因死亡率的相關性。方法：使用2個獨立的台灣老人社區世代 (community cohorts) 之前瞻性研究 (perspective study) (n=2065)，其血鉀值介於2.8-5.6 mmol/L。本研究將個案分成4組，低血鉀 (low serum potassium, 2.8-3.4 mmol/L)、正常低血鉀 (low-normal serum potassium, 3.4–3.8 mmol/L)、正常血鉀 (normal serum potassium, 3.9–4.4 mmol/L)、及正常高血鉀 (high-normal serum potassium, 4.5–5.6 mmol/L)。我們使用Cox proportional hazards model來比較不同血鉀組和死亡率的相關性。結果：基線血鉀和所有死因及心血管疾病死亡率呈現U型的關係，而血鉀落在3.9到4.4 mmol/L之間病人的死亡率最低。和正常血鉀相比，正常低血鉀組其全死因 (HR, 1.3; 95% CI, 1.0–1.6) 及心血管疾病死亡率 (HR, 1.6; 95% CI, 1.1–2.3) 顯著較高。正常高血鉀組死亡率較正常血鉀組高，但未達統計上的顯著意義。結論：根據本研究結果，我們建議正常低血鉀亦可作為老人存活預後較差的警示指標。 研究二、含鉀含鎂低鈉鹽介入對中風患者癒後的影響 (多中心臨床試驗) 背景/目的：低血鎂是糖尿病風險以及腦中風嚴重度之指標，近年來針對急性梗塞性中風病人靜脈注射硫酸鎂之研究受到相當重視，但結果並不肯定。本研究室先前針對榮民之家的社區老人，長期進行含鉀低鈉鹽取代一般食鹽之介入研究，發現可以降低41%的心血管疾病死亡率。食鹽是一個好的礦物質載體，本研究，擬進一步探討，以食鹽為載體，長期改善鉀和鎂的營養，是否能夠更進一步，改善中風病人之預後。目的：本研究目的為評估含鉀含鎂低鈉鹽對中風病人神經功能表現的影響。方法：本多中心臨床試驗，包括三個組別：一般食鹽組、含鉀低鈉鹽組、和含鉀含鎂低鈉鹽組。我們在個案出院時及回診時提供適量的食鹽，並自收案起持續追蹤個案的NIHSS、Barthel Index (BI) 及mRS至6個月，若個案的mRS≦1會被視為較佳的神經功能指標。我們以Generalized Estimating Equations (GEE) 來檢驗食鹽的使用和神經功能的相關性，並校正年齡、性別和用藥。結果：和基線相比，不論是在第三個月 (3rd month) 或第六個月 (6th month) 回診時，含鉀含鎂低鈉鹽組其個案mRS≦1的比例顯著較一般食鹽組及含鉀低鈉鹽組高 (3rd month: p=0.01, 0.03或6th month: p=0.005, 0.01)。和一般食鹽相比，含鉀含鎂低鈉鹽組可以顯著增加中風病人神經功能表現的勝算比 (odds ratio, 1.8; p=0.035)。結論：本研究建議，長期管理腦中風病人之鎂營養狀況可以改善中風病人的神經功能表現，在病人未能有效提升飲食鎂攝食量時，含鎂含鉀低鈉鹽為一有效礦物質鎂的添加載體。Stroke is among the leading causes of death, which can cause to permanent neurological deficits and affect quality of life. Potassium and magnesium, two essential minerals, play important roles in the pathogenesis of hypertension, diabetes, and stroke. Dietary sodium excess contributes to the blood pressure elevation with age and increases the risk of stroke. Potassium can counteract the effect of sodium on hypertension and protect against stroke mortality. Magnesium nutriture has been associated with diabetes risk and severity of stroke symptom. Intravenous provision of magnesium to acute phase stroke patients has been vigorously studied but with controversial findings. It is lacking studies to investigate the association between nutritional status of these minerals and the long-term cerebrovascular outcomes of high risk groups such as elderly and stroke patients. Study 1. Association study between serum potassium and risk of cardiovascular and all-cause death in community-based elderly （Prospective study） Background/Purpose: Several studies have already reported that serum potassium (SK) correlated inversely with adverse event among patients with pre-existing cardiovascular disease and impaired renal function; less is known about the prognostic value of SK at the normal range in community-based elderly individuals. Objective: This study aimed to examine whether low normal or high normal SK value was associated with cardiovascular and all-cause mortalities in elderly people. Methods: Perspective study using two independent elderly Taiwanese community cohorts which included 2065 subjects with relatively normal SK values (2.8-5.6 mmol/L). Subjects were grouped into: low (2.8-3.4 mmol/L), low-normal SK (3.5–3.8 mmol/L), normal (3.9–4.4 mmol/L), and high-normal SK (4.5–5.6 mmol/L). Proportional hazards model was applied to compare the association between SK concentration groups and mortality. Results: The relationship between baseline SK and all-cause and cardiovascular mortality was U-shaped, with the lowest mortality rates observed in patients with SK levels of 3.9 to 4.4 mmol/L. The low-normal SK group had significantly higher risk of all-cause (HR, 1.3; 95% CI, 1.0–1.6) and cardiovascular mortalities (HR, 1.6; 95% CI, 1.1–2.3) than the normal SK group. The high normal SK group had higher but non-significant risk compared to the normal. Conclusion: Our findings suggest that low-normal SK may be used as a marker of poor survival for elderly outpatient cares. Study 2. The effect of intervention with potassium and/ or magnesium-enriched salt on neurological performance of stroke patients (Multi-center clinical trial) Background: Stroke is one of the leading causes of mortality and neurological deficits. Adequate dietary potassium is associated with reduced risk of hypertension and stroke. Our previous 3.5-year intervention trial in the elderly demonstrated a 41%-reduction in cardiovascular mortality from switching to potassium-enriched salt. Since dietary magnesium has been associated with lowered diabetes/stroke risk in human and neuroprotection in animal and salt is a good carrier for mineral; it is justifiable to study whether further enriching salt with magnesium may provide additional benefit for stroke recovery, at the level near but not beyond the daily recommended intake level (DRI). Methods: A multi-centered randomized controlled trial was carried out with three arms: (1) regular salt (Na salt), (2) potassium-enriched salt (K salt), and (3) potassium and magnesium-enriched salt (K/Mg salt). The NIHSS, Barthel Index (BI) and mRS were evaluated at baseline, 3 month, and 6 month. Results: A significantly higher percentage of patients with mRS≦1was observed for both the K/Mg and the K groups at 3rd (p=0.01 and 0.03, respectively) and 6th months (p=0.005 and 0.01) than baseline. This phenomenon is not apparent in the Na group. The K/Mg group had a significantly increased odds ratio of achieving good neurological performance defined by a combination of 3 indices, compared with the Na group (odds ratio, 1.77; p=0.035) and with the K group (odds ratio, 1.70; p-0.057). Conclusion: This study suggests that long-term replenishing magnesium to reach DRI is beneficial for stroke patients to recover from neurological injuries