During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic ...levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance.
On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19-specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 95% confidence interval (CI) 1.08 to 1.21), female sex (1.58 1.38 to 1.82), low educational level (primary education versus higher vocational/university 1.21 1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 1.80 to 2.22), unemployment (versus employed 2.29 1.54 to 3.39), smoking (1.34 1.08 to 1.65), concern about contracting COVID-19 (per level increase 1.28 1.19 to 1.38) and symptoms of depression (per point increase 1.13 1.11 to 1.14) and anxiety (per point increase 1.16 1.14 to 1.18). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population.
In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences.
The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and ...potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.
Aims/hypothesis
Previous studies have found an association between serum magnesium and incident diabetes; however, this association may be due to reverse causation, whereby diabetes may induce ...urinary magnesium loss. In contrast, in prediabetes (defined as impaired fasting glucose), serum glucose levels are below the threshold for urinary magnesium wasting and, hence, unlikely to influence serum magnesium levels. Thus, to study the directionality of the association between serum magnesium levels and diabetes, we investigated its association with prediabetes. We also investigated whether magnesium-regulating genes influence diabetes risk through serum magnesium levels. Additionally, we quantified the effect of insulin resistance in the association between serum magnesium levels and diabetes risk.
Methods
Within the population-based Rotterdam Study, we used Cox models, adjusted for age, sex, lifestyle factors, comorbidities, kidney function, serum levels of electrolytes and diuretic use, to study the association between serum magnesium and prediabetes/diabetes. In addition, we performed two mediation analyses: (1) to study if common genetic variation in eight magnesium-regulating genes influence diabetes risk through serum magnesium levels; and (2) to quantify the proportion of the effect of serum magnesium levels on diabetes that is mediated through insulin resistance (quantified by HOMA-IR).
Results
A total of 8555 participants (mean age, 64.7 years; median follow-up, 5.7 years) with normal glucose levels (mean ± SD: 5.46 ± 0.58 mmol/l) at baseline were included. A 0.1 mmol/l decrease in serum magnesium level was associated with an increase in diabetes risk (HR 1.18 95% CI 1.04, 1.33), confirming findings from previous studies. Of interest, a similar association was found between serum magnesium levels and prediabetes risk (HR 1.12 95% CI 1.01, 1.25). Genetic variation in
CLDN19
,
CNNM2, FXYD2, SLC41A2,
and
TRPM6
significantly influenced diabetes risk (
p
< 0.05), and for
CNNM2, FXYD2, SLC41A2
and
TRPM6
this risk was completely mediated by serum magnesium levels. We found that 29.1% of the effect of serum magnesium levels on diabetes was mediated through insulin resistance, whereas for prediabetes 13.4% was mediated through insulin resistance.
Conclusions/interpretation
Low serum magnesium levels are associated with an increased risk of prediabetes and this increased risk is similar to that of diabetes. Furthermore, common variants in magnesium-regulating genes modify diabetes risk through serum magnesium levels. Both findings support a potential causal role of magnesium in the development of diabetes, where the hypothesised pathway is partly mediated through insulin resistance.
Background Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with ...hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. Study Design Prospective cohort study. Setting & Participants 9,818 individuals from the general population (Rotterdam Study). Predictor PPI use and H2RA use compared to no use. Outcomes & Measurements Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. Results Serum magnesium level was 0.022 mEq/L lower in PPI users (n = 724; 95% CI, −0.032 to −0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n = 36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n = 270), PPI use was associated with a further increased risk of hypomagnesemia (n = 5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n = 250) also had a lower serum magnesium level (−0.016 95% CI, −0.032 to −0.002 mEq/L) and increased risk of hypomagnesemia (n = 12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. Limitations Cross-sectional analysis with single serum magnesium measurement. Conclusions PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.
Purpose
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.
Methods
The study performed a cross‐sectional analysis within 9820 participants from the prospective Rotterdam Study. Hypomagnesaemia was defined as a serum magnesium level ≤0.72 mmol/L. Participants were categorized by defined daily dose (DDD), and all analyses were adjusted for age, sex, BMI, eGFR, serum potassium levels, proton pump inhibitor use, and comorbidities.
Results
Loop diuretic use was associated with higher serum magnesium levels (<1 DDD: 0.004 mmol/L 95% CI: −0.008; 0.017; 1 DDD: 0.023 mmol/L 95% CI: 0.013; 0.032; >1 DDD: 0.043 mmol/L 95% CI: 0.028; 0.057). Thiazide diuretic use was associated with lower serum magnesium levels (<1 DDD: −0.013 mmol/L 95% CI: −0.023; −0.002; ≥1 DDD: −0.018 mmol/L 95% CI: −0.028; −0.010), resulting in an increased odds ratio of hypomagnesaemia of 3.14 (95% CI: 1.67; 5.92) and 2.74 (95% CI: 1.57; 4.77), respectively. These effects were predominantly seen in participants using diuretics for more than 390 days. Combining thiazide diuretics with a potassium‐sparing agent was not associated with lower serum magnesium levels or hypomagnesaemia.
Conclusions
Thiazide diuretic use is associated with lower serum magnesium levels and an increased risk of hypomagnesaemia. This increased risk is not seen in participants using a combination of thiazide diuretics with a potassium‐sparing agent. The use of loop diuretics is not associated with an increased risk of hypomagnesaemia.
Background Multimorbidity poses a major challenge for care coordination. However, data on what non-communicable diseases lead to multimorbidity, and whether the lifetime risk differs between men and ...women are lacking. We determined sex-specific differences in multimorbidity patterns and estimated sex-specific lifetime risk of multimorbidity in the general population. Methods We followed 6,094 participants from the Rotterdam Study aged 45 years and older for the occurrence of ten diseases (cancer, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, diabetes, dementia, asthma, heart failure, parkinsonism). We visualised participants' trajectories from a single disease to multimorbidity and the most frequent combinations of diseases. We calculated sex-specific lifetime risk of multimorbidity, considering multimorbidity involving only somatic diseases (1) affecting the same organ system, (2) affecting different organ systems, and (3) multimorbidity involving depression. Results Over the follow-up period (1993-2016, median years of follow-up 9.2), we observed 6334 disease events. Of the study population, 10.3% had three or more diseases, and 27.9% had two or more diseases. The most frequent pair of co-occurring diseases among men was COPD and cancer (12.5% of participants with multimorbidity), the most frequent pair of diseases among women was depression and dementia (14.9%). The lifetime risk of multimorbidity was similar among men (66.0%, 95% CI: 63.2-68.8%) and women (65.1%, 95% CI: 62.5-67.7%), yet the risk of multimorbidity with depression was higher for women (30.9%, 95% CI: 28.4-33.5%, vs. 17.5%, 95% CI: 15.2-20.1%). The risk of multimorbidity with two diseases affecting the same organ is relatively low for both sexes (4.2% (95% CI: 3.2-5.5%) for men and 4.5% (95% CI: 3.5-5.7%) for women). Conclusions Two thirds of people over 45 will develop multimorbidity in their remaining lifetime, with women at nearly double the risk of multimorbidity involving depression than men. These findings call for programmes of integrated care to consider sex-specific differences to ensure men and women are served equally. Keywords: Sex differences, Multimorbidity, Risk of multimorbidity, Cohort study, Population study, Chronic diseases
To determine if serum magnesium levels are associated with the risk of all-cause dementia and Alzheimer disease.
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.
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).
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.
The Rotterdam Study is a population-based cohort study, started in 1990 in the district of Ommoord in the city of Rotterdam, the Netherlands, with the aim to describe the prevalence and incidence, ...unravel the etiology, and identify targets for prediction, prevention or intervention of multifactorial diseases in mid-life and elderly. The study currently includes 17,931 participants (overall response rate 65%), aged 40 years and over, who are examined in-person every 3 to 5 years in a dedicated research facility, and who are followed-up continuously through automated linkage with health care providers, both regionally and nationally. Research within the Rotterdam Study is carried out along two axes. First, research lines are oriented around diseases and clinical conditions, which are reflective of medical specializations. Second, cross-cutting research lines transverse these clinical demarcations allowing for inter- and multidisciplinary research. These research lines generally reflect subdomains within epidemiology. This paper describes recent methodological updates and main findings from each of these research lines. Also, future perspective for coming years highlighted.
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.
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