See article vol. 28: 329-337 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is recognized as a key factor of familial hypercholesterolemia since 2003. Afterward, the association of PCSK9 ...genetic variance was found with low-density lipoprotein (LDL) cholesterol level and risk of coronary heart disease (CHD), and PCSK9 has been a novel therapeutic target. Recently, two monoclonal antibodies to PCSK9 (Evolocumab and Airocumab) have been available especially for high cholesterol patients resistant to statins and other lipid-lowering medication, and clinical and research interests are increasing on PCSK9. Although PCSK9 has a vital role in lipid metabolism and CHD risk, the interpretation of serum PCSK9 level remains not well known.
Sleep apnea and type 2 diabetes Muraki, Isao; Wada, Hiroo; Tanigawa, Takeshi
Journal of diabetes investigation,
September 2018, Volume:
9, Issue:
5
Journal Article
Peer reviewed
Open access
The aim of the present review was to clarify the association between obstructive sleep apnea (OSA) and type 2 diabetes, and discuss the therapeutic role of continuous positive airway pressure (CPAP) ...in type 2 diabetes. OSA patients are more likely than non‐OSA populations to develop type 2 diabetes, while more than half of type 2 diabetes patients suffer from OSA. Similar to Western countries, in the East Asian population, the association between these two disorders has also been reported. CPAP is the primary treatment for OSA, but the effect of CPAP on comorbid diabetes has not been established. CPAP improved glucose metabolism determined by the oral glucose tolerance test in OSA patients, and several studies have shown that CPAP improves insulin resistance, particularly in obese populations undergoing long‐term CPAP. Diabetes is associated with other sleep‐related manifestations as well, such as snoring and excessive daytime sleepiness. Snoring is associated with the development of diabetes, and excessive daytime sleepiness appears to modify insulin resistance. Well‐designed studies are required to clarify the therapeutic effect of CPAP on diabetes. As both diabetes and OSA lead to cardiovascular disease, clinicians and healthcare professionals should be aware of the association between diabetes and OSA, and should take CPAP and health‐related behaviors into consideration when treating patients with diabetes and/or OSA.
Obstructive sleep apnea (OSA) leads to sympathetic neural activation, systemic inflammation, oxidative stress loading, and changes in hormonal systems, whereas diabetes affects sleep conditions via the central respiratory system. OSA treatment, such as continuous positive airway pressure, resolves some of these factors, and may exert a therapeutic effect on diabetes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: Limited epidemiological evidence has suggested a positive relationship between night shift work and the risk of cancer. Herein, we investigated the prospective association between ...different forms of work schedule and the risk of numerous cancers and all-cause cancer among Japanese men and women.Methods: This cohort study included 45,390 working men and women aged 40–79 years and registered in the Japan Collaborative Cohort Study (JACC Study). The Cox proportional hazards models were used to calculate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for incident cancer among those who reported engagement in night work and rotating shift work for their longest occupations compared with day work.Results: Within a median follow-up duration of 14.2 years, 2,283 (9.4%) men and 1,309 (4.5%) women developed cancer. Among men, rotating shift work was significantly associated with increased risk of esophageal cancer (HR 2.47; 95% CI, 1.42–4.31) and decreased risk of liver cancer (HR 0.54; 95% CI, 0.30–0.98). Also, rotating shift work tended to be associated with the increased risk of prostate cancer (HR 1.42; 95% CI, 0.95–2.12). Night work and rotating shift work were not related to the risk of all-cause cancer in either sex.Conclusion: Rotating shift work might contribute to the increased risk of esophageal cancer and prostate cancer and the decreased risk of liver cancer among Japanese men.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Increased fruit and vegetable intake lowers blood pressure in short-term interventional studies. However, data on the association of long-term intake of fruits and vegetables with hypertension risk ...are scarce. We prospectively examined the independent association of whole fruit (excluding juices) and vegetable intake, as well as the change in consumption of whole fruits and vegetables, with incident hypertension in 3 large longitudinal cohort studies: Nurses' Health Study (n=62 175), Nurses' Health Study II (n=88 475), and Health Professionals Follow-up Study (n=36 803). We calculated hazard ratios and 95% confidence intervals for fruit and vegetable consumption while controlling for hypertension risk factors. Compared with participants whose consumption was ≤4 servings/week, the pooled hazard ratios among those whose intake was ≥4 servings/day were 0.92(0.87-0.97) for total whole fruit intake and 0.95(0.86-1.04) for total vegetable intake. Similarly, compared with participants who did not increase their fruit or vegetable consumption, the pooled hazard ratios for those whose intake increased by ≥7 servings/week were 0.94(0.90-0.97) for total whole fruit intake and 0.98(0.94-1.01) for total vegetable. Analyses of individual fruits and vegetables yielded different results. Consumption levels of ≥4 servings/week (as opposed to <1 serving/month) of broccoli, carrots, tofu or soybeans, raisins, and apples was associated with lower hypertension risk. In conclusion, our results suggest that greater long-term intake and increased consumption of whole fruits may reduce the risk of developing hypertension.
Background: Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined ...comprehensively.Methods: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (<40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fractions (PAFs) were estimated using the hazard ratios and the prevalence of risk factors among cases.Results: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage, while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic, and large-artery occlusive strokes were 36.7%, 44.5%, and 61.5%, respectively.Conclusion: Although there are differences according to subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Background: The impact of weight change, physical activity, and sedentary behavior on endometrial cancer risk among the Asian population is uncertain. We investigated the association of those factors ...with endometrial cancer risk among Japanese women with a low body mass index level.Methods: We performed a large-scale nationwide cohort study consisting of 33,801 female participants aged 40–79 years. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident endometrial cancer.Results: The mean body mass index of participants was 22.8 kg/m2. During a median follow-up of 14.8 years, 79 participants developed endometrial cancer. After adjustment for potential confounding factors, body mass index over 23.0 kg/m2 was linearly associated with the risk of endometrial cancer. The HR per 5 kg/m2 increase was 1.80 (95% CI, 1.28–2.54). Weight increment ≥+5 kg since age 20 was associated with an increased risk of endometrial cancer compared to a weight change of −5 to <+5 kg (multivariable HR 1.96; 95% CI, 1.12–3.40). Compared with females who were mainly sitting at the worksite, those who were mainly standing and moving were at lower risk; the multivariable HRs were 0.79 (95% CI, 0.39–1.59) and 0.46 (95% CI, 0.22–0.97), respectively (P for trend = 0.042). Hours of physical exercise, daily walking, and TV viewing were not associated with endometrial cancer risk.Conclusions: Overweight and weight gain were positively associated with the risk of endometrial cancer, while worksite physical activity was inversely associated with the risk.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Aims: We investigated the optimal cut-off points of nonfasting and fasting triglycerides in Japanese individuals with lower average triglyceride levels than westerners. Methods: Residents aged 40–69 ...years without a history of ischemic heart disease or stroke were enrolled between 1980 and 1994 and followed. Serum triglyceride concentrations were measured from 10851 nonfasting (＜8 h after meal) and 4057 fasting (≥ 8 h) samples. As a prerequisite, we confirmed the shape of a receiver operating characteristic (ROC) curves, the area under ROC curves (AUC), and the integrated time-dependent AUC. We identified optimal cut-off points for incident ischemic heart disease based on C-statistic, Youden index, and Harrell’s concordance statistic. We used dichotomized concentrations of triglycerides via the univariate logistic regression and Cox proportional hazards regression models. We also calculated multivariable hazard ratios and population attributable fractions to evaluate the optimal cut-off points.Results: Nonfasting and fasting optimal cut-off points were 145 mg/dL and 110 mg/dL, with C-statistic of 0.594 and 0.626, Youden index of 0.187 and 0.252, and Harrell’s concordance statistic of 0.590 and 0.630, respectively. The corresponding multivariable hazard ratios of ischemic heart disease were 1.43 (95%CI 1.09–1.88) and 1.69 (1.03–2.77), and the corresponding population attributable fractions were 16.1% (95%CI 3.3–27.2%) and 24.6 (−0.3–43.3).Conclusion: The optimal cut-off points of nonfasting and fasting triglycerides in the Japanese general population were 145 mg/dL and 110 mg/dL, respectively, lower than the current cut-off points recommended in the US and Europe.
Aims: We examined whether secondhand smoke exposure in childhood affects the risk of coronary heart disease (CHD) in adulthood.Methods: In the Japan Collaborative Cohort Study, we analyzed data on ...71,459 participants aged 40–79 years, with no history of CHD, stroke, or cancer at baseline (1988–1990) and who completed a lifestyle questionnaire including the number of smoking family members in childhood (0, 1, 2, and 3+ members) and followed them up until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of CHD mortality according to the number of smoking family members in childhood.Results: During the median 18.9 years’ follow-up, 955 CHD deaths were reported. There was a dose–response relationship between the number of smoking family members at home and CHD mortality among middle-aged individuals (40–59 years); the multivariable HRs (95% CIs) were 1.08 (0.76–1.54) for 1, 1.35 (0.87–2.08) for 2, and 2.49 (1.24–5.00) for 3+ smoking family members compared with 0 members (p for trend=0.03). The association for 3+ smoking family members among the middle-aged group was more evident in men than in women (the multivariable HRs 95% CIs were 2.97 1.34–6.58 and 1.65 0.36–7.52, respectively) and more evident in non-current smokers than in current smokers (the multivariable HRs 95% CIs were 4.24 1.57–11.45 and 1.93 0.72–5.15, respectively).Conclusions: Secondhand smoke exposure in childhood was associated with an increased risk of CHD mortality in adulthood, primarily in middle-aged men and non-current smokers.
Abstract
Aims
Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause ...mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium.
Methods and results
We performed an individual-level data meta-analysis of 27 international cohorts 10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD) in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4–4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 95% confidence interval (CI) 1.15–1.29 at 5.5 mmol/L and 1.49 (95% CI 1.26–1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin–angiotensin–aldosterone system inhibitor use, and across cohorts.
Conclusions
Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.
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