Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

BACKGROUND: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. OBJECTIVES: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. METHODS: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. RESULTS: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. CONCLUSION: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.

Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population-A Prospective Population Study.

BACKGROUND: Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population. METHODS: Participants (aged 48-76 years) from the general population study "Copenhagen City Heart Study" (n = 5916) were studied. Participants were divided into groups according to baseline values of plasma potassium (potassium): hypokalemia (<3.7 mmol/L, n = 758), normokalemia (3.7-4.5 mmol/L, n = 4973), and high potassium (>4.5 mmol/L, n = 185). Hypokalemia was further divided as potassium <3.4 mmol/L and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and nonfatal validated ischemic stroke. The secondary endpoint was acute myocardial infarction (AMI). We adjusted for conventional risk factors, diuretics, and atrial fibrillation at baseline. RESULTS: Mean potassium in the hypokalemic group was 3.5 mmol/L (range, 2.6-3.6 mmol/L) and was associated (P < 0.05) with increased systolic blood pressure, higher CHA2DS2-VASc score, and increased use of diuretics as compared with normokalemia. Baseline atrial fibrillation was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.00-1.98). The subgroup with potassium <3.4 mmol/L had higher stroke risk (HR 2.10; 95% CI, 1.19-3.73) and mortality risk (HR 1.32; 95% CI, 1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI, and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high potassium. CONCLUSION: In a general population mild hypokalemia is associated with increased stroke risk and, to a lesser degree, increased mortality risk.

Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common clinical arrhythmia and a major cause of cardiovascular morbidity and mortality. Among the gene defects previously associated with AF is a gain of function of the slowly activating delayed rectifier potassium current IKs, secondary to mutations in KCNQ1. Coexpression of KCNE5, the gene encoding the MiRP4 beta-subunit, has been shown to reduce IKs. OBJECTIVE: The purpose of this study was to test the hypothesis that mutations in KCNE5 are associated with AF in a large cohort of patients with AF. METHODS: One-hundred fifty-eight patients with AF were screened for mutations in the coding region of KCNE5. RESULTS: A missense mutation involving substitution of a phenylalanine for leucine at position 65 (L65F) was identified in one patient. This patient did not have a history of familial AF, and neither KCNQ1 nor KCNE2 mutations were found. Transient transfection of Chinese hamster ovary (CHO) cells expressing IKs(KCNQ1+KCNE1) with KCNE5 suppressed the developing and tail currents of IKs in a concentration-dependent manner. Transient transfection with KCNE5-L65F failed to suppress IKs, yielding a current indistinguishable from that recorded in the absence of KCNE5. Developing currents recorded during a test pulse to +60 mV and tail currents recorded upon repolarization to -40 mV both showed a significant concentration-dependent gain of function in IKs with expression of KCNE5-L65F vs KCNE5-WT. CONCLUSION: The results of this study suggest that a missense mutation in KCNE5 may be associated with nonfamilial or acquired forms of AF. The arrhythmogenic mechanism most likely is a gain of function of IKs.