Brenda C.T. Kieboom

Serum Magnesium and the Risk of Death From Coronary Heart Disease and Sudden Cardiac Death

Background Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population‐based Rotterdam Study, with adjudicated end points and long‐term follow‐up. Methods and Results Nine‐thousand eight‐hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow‐up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70–0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81–0.88 mmol/L). Low serum magnesium (≤0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09–1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12–2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima‐media thickness: +0.013 mm, 95% CI 0.005–0.020) and increased QT‐interval, mainly through an effect on heart rate (RR‐interval: −7.1 ms, 95% CI −13.5 to −0.8). Additional adjustments for carotid intima‐media thickness and heart rate did not change the associations with CHD mortality and SCD. Conclusions Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima‐media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks.

Pedobarographic analysis and quality of life after lisfranc fracture dislocation

Background: Few studies on tarsometatarsal fracture dislocations report on plantar pressure analysis and quality of life. The primary aim of this study was to determine the added value of plantar pressure analysis. The secondary aim was to determine quality of life and functional outcome. Materials and Methods: With a median followup of 76 months, 26 patients with an isolated Lisfrane injury participated. The Short Form 36 (SF-36) was used to determine the health related quality of life. Functional outcome was assessed with the American Orthopaedic Foot Ankle Society (AOFAS) midfoot score and a Visual Analog Scale (VAS). A Wilcoxon Signed Rank test was used to assess whether plantar pressure and foot position variables differed between the injured and uninjured foot. Correlations between outcome data were identified using Spearman Rank Correlation. Results: With respect to the plantar pressure analysis, a reduced contact time of the forefoot was found for the injured foot compared with the contralateral side (p = 0.045). The injured side showed reduced contact surface of the forefoot (p = 0.048) and an increased contact surface for the midfoot (p = 0.019). The latter was paralleled by higher maximum pressures at the midfoot (p = 0.016). Patients reported a median score of 101 for the SF-36, 72 for the AOFAS midfoot score, and 7 for the VAS. Conclusion: Plantar pressure measurements showed an adjusted walking pattern. Despite a fair outcome score, the quality for life of patients following a Lisfranc fracture dislocation returned to normal compared with normative data for the general population. Level of Evidence: IV, Retrospective Case Control Series

Serum magnesium is associated with the risk of dementia

Objective: To determine if serum magnesium levels are associated with the risk of all-cause dementia and Alzheimer disease. Methods: Within the prospective population-based Rotterdam Study, we measured serum magnesium levels in 9,569 participants, free from dementia at baseline (1997–2008). Participants were subsequently followed up for incident dementia, determined according to the DSM-III-R criteria, until January 1, 2015. We used Cox proportional hazard regression models to associate quintiles of serum magnesium with incident all-cause dementia. We used the third quintile as a reference group and adjusted for age, sex, Rotterdam Study cohort, educational level, cardiovascular risk factors, kidney function, comorbidities, other electrolytes, and diuretic use. Results: Our study population had a mean age of 64.9 years and 56.6% were women. During a median follow-up of 7.8 years, 823 participants were diagnosed with all-cause dementia. Both low serum magnesium levels (≤0.79 mmol/L) and high serum magnesium levels (≥0.90 mmol/L) were associated with an increased risk of dementia (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.02–1.69, and HR 1.30, 95% CI 1.02–1.67, respectively). Conclusions: Both low and high serum magnesium levels are associated with an increased risk of all-cause dementia. Our results warrant replication in other population-based studies.

Thiazide but not loop diuretics is associated with hypomagnesaemia in the general population

Hypomagnesaemia has been associated with various adverse outcomes. Loop and thiazide diuretics promote urinary magnesium excretion. However, it is unknown if this links to hypomagnesaemia. We study if loop or thiazide diuretic use affects serum magnesium levels and if it associates with hypomagnesaemia. In addition, we study the effect of combining a potassium‐sparing diuretic with a thiazide diuretic on the presence of hypomagnesaemia.

Standard process-oriented workflow introduces pre-analytical error when used in large study sample batches

The quality of a laboratory measurement can be influenced by various processes within the pre-analytical, analytical and post-analytical phase. Over the past years, advances in automatization and quality control measures have improved the quality and reduced the total number of errors to only 0.31% [1, 2]. When using laboratory measurements for research, even a small bias, which may not be clinically relevant, can dilute or inflate results leading to false results and incorrect interpretation of risk estimates. Knowing the cause of such errors is important to assess the potential impact on study results and ultimately to prevent these errors. In general, the cause of errors in laboratory measurements used for research does not differ from measurements in routine clinical practice and includes interference with additives in the blood collection tube and the timely processing of samples [3, 4]. However, within the Rotterdam Study, a prospective population-based cohort study [5], we observed a bias in the serum sodium levels measurements not seen in routine clinical work. From a specific set of snap frozen, stored samples of 9894 participants, a total of 19 tests was ordered (for characteristics see Table 1). Measurements were performed using a Cobas 8000 analyzer (Roche Diagnostics, Mannheim, Germany) with intelligent sample routing algorithm [6]. The software controls the flow and logistics of the samples in the system and enables the fastest turnaround time (TAT) for routine clinical samples, maximizing sample throughput based on the real-time workload situation of each module and the entire unit. Within the samples, the mean serum sodium concentration was 142.1 mmol/L, whereas it was expected to be approximately 140.0 mmol/L given the fact that this study was performed within a general population and serum sodium is regulated within a narrow range (137–142 mmol/L) [7]. Serum sodium levels were normally distributed with a standard deviation of 3.1 mmol/L and a range of 124–171 mmol/L. Within 5207 of the 9894 participants, serum sodium had been measured 7 years earlier, showing a mean serum sodium concentration of 140.1 mmol/L, with a standard deviation of 4.1 mmol/L and a range of 124–160 mmol/L. Characteristics of the current study population were compared with the previous round, but no major differences were observed, which could explain the shift toward higher serum sodium levels (data not shown). Internal and external quality control reports from that specific time period were examined and showed no *Corresponding author: Bruno H. Stricker, MMed, PhD, Department of Internal Medicine and Epidemiology, Erasmus MC – University Medical Center Rotterdam, P.O. Box 2040, 3000 Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands, Phone: +31 (0)10-7044294, Fax: +31 (0)10-7044657, E-mail: b.stricker@erasmusmc.nl Brenda C.T. Kieboom: Department of Epidemiology, Erasmus MC – University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC – University Medical Center Rotterdam, Rotterdam, The Netherlands; and Inspectorate of Health Care, Utrecht, The Netherlands. http://orcid.org/0000-0001-9075-222X Ewout J. Hoorn, Robert Zietse and Robin P. Peeters: Department of Internal Medicine, Erasmus MC – University Medical Center Rotterdam, Rotterdam, The Netherlands Christian Ramakers and Yolanda B. de Rijke: Department of Clinical Chemistry, Erasmus MC – University Medical Center Rotterdam, Rotterdam, The Netherlands Frank J.A. van Rooij, M. Arfan Ikram, Albert Hofman, Cornelia M. van Duijn and Jan Heeringa: Department of Epidemiology, Erasmus MC – University Medical Center Rotterdam, Rotterdam, The Netherlands