Varicose veins are associated with an increased risk of mitral valve regurgitation: a nationwide population-based cohort study.

BACKGROUND: Varicose veins (VV) and mitral valve regurgitation (MR) are both common diseases. The aim was to investigate whether VV are associated with an increased risk of MR. METHODS: We conducted a nationwide cohort study to assess the association between VV and risk of developing MR. Drawn from the Taiwan National Health Insurance Research Database (NHIRD), the records of 56,898 patients with VV (the VV cohort) and 56,898 propensity score-matched patients without VV (the non-VV cohort) in the years 2007 to 2015 were identified. Follow-up duration was calculated from the date of entry in the cohort until the occurrence of a first MR diagnosis, death, or the end of the observation period (December 31, 2015), whichever occurred first. Hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to estimate the association between VV and MR risks. RESULTS: After multivariable adjustment, VV was associated with an increased risk of MR (adjusted HR, 1.63; 95% CI: 1.52-1.74). Notably, significant associations between VV and MR risk were evident in both genders and in all age groups. A trend of significant increase of MR risk was also observed with increasing frequency of annual clinical visits for VV. Within the VV cohort, the subgroup of MR presence had higher incidences of atrial fibrillation, heart failure, valve-related surgeries, and mortality (P<0.001). CONCLUSIONS: This population-based cohort study revealed that VV was associated with an increased risk of MR in a Taiwanese population. Vigilance of MR existence should be emphasized in patients of VV due to its potentially poor long-term outcomes.

The clinical and sleep manifestations in children with FOXG1 syndrome.

FOXG1 syndrome is a rare neurodevelopmental disorder associated with severe cognitive dysfunction, autistic behavior, and early-onset hyperkinetic movement disorders. Patients have also been reported to experience sleep disturbances. However, these findings are mainly based on subjective caregivers' reports, and limited by small case numbers. Moreover, no studies using objective evaluation tools, such as actigraphy, have been reported. We analyzed the clinical and sleep manifestations of children with FOXG1 syndrome registered in the FOXG1 Research Foundation Patient Registry database. A total of 258 individuals with FOXG1 syndrome were included in this research. 132 (51.16%) had sleep disturbances. The more impaired of language acquisitions (absence of speech, OR: 3.99, 95%CI = 1.69-9.42, p = 0.002), hyperkinetic movement disorders (OR: 2.64, 95%CI = 1.34-5.20 p = 0.005) and feeding difficulties (OR: 2.81, 95% CI = 1.52-5.19, p = 0.001) were significantly associated with an increase in odds of sleep disturbance after adjusting for age, sex, and antiepileptic drugs. We also performed sleep studies on six individuals with FOXG1 syndrome using The Children's Sleep Habits Questionnaire (CSHQ), the Sleep Disturbance Scale for Children (SDSC), and 7-day data from Actiwatch. The Pittsburgh Sleep Quality Index (PSQI) and 7-day data from Actiwatch were also used to evaluate the sleep condition of their parents. The CSHQ scores revealed bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night-waking, and parasomnia. Sleep-wake transition disorders and disorders of initiating and maintaining sleep were also suggested by the SDSC scores. The children's actigraphy revealed short sleep durations, impaired sleep efficiency, longer wake after sleep onset, and frequent night-waking. All caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration. Sleep disturbances, especially in initiating and maintaining sleep, are common in individuals with FOXG1 syndrome and their caregivers. Sleep disorders in patients with FOXG1 syndrome and their caregivers should be investigated.

Association between atopic dermatitis and colorectal cancer risk: A nationwide cohort study.

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14-1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.

Statin use and the risk of renal cell carcinoma: national cohort study.

Statins are a therapeutic drug with reducing plasma cholesterol levels and have been linked with potential antitumor effects. However, epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent. This cohort study aimed to examine this association in an Asian population. We identified patients who filled initial prescriptions for statins in the inpatient and ambulatory care order files from Taiwan's National Health Insurance Research Database between January 1, 1998 and December 31, 2005 as the statin users cohort (n=14,067). The comparison cohort comprised of patients who had not taken any statin in the previous years prior to January 1, 1998 or had used statins for less than 28 cumulative defined daily doses between January 1, 1998 and December 31, 2005 (n=56 268). The outcome of interest was pathologically verified RCC occurred between January 1, 1999 and December 31, 2013. The Fine-Gray competing risk model was fitted to estimate HRs accompanying 95% CI. Patients with the use of statins had a significantly lower risk of RCC as compared with the non-users cohort, yielding an adjusted HR of 0.64 (95% CI, 0.38 to 0.87). Moreover, we found a significant inverse association between cumulative statin use and the risk of RCC. Further, the inverse association between statin use and risk of RCC was evident in both sexes. This population-based cohort study provides longitudinal evidence that the use of statins was associated with a reduced risk of RCC.

Correlation between kidney transplantation and colorectal cancer in hemodialysis patients: A nationwide, retrospective, population-based cohort study.

BACKGROUND: Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort. METHODS: We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan's National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan-Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients. RESULTS: The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P < 0.001). After adjusting for potential confounders, the exposed cohort exhibited a significantly increased risk of CRC compared with the non-exposed cohort (adjusted HR, 1.34; 95% CI, 1.11-1.62). CONCLUSIONS: Hemodialysis patients undergoing KT have a significantly higher risk of CRC than those not undergoing KT. Cancer should continue to be a primary focus of prevention during KT.

Elevated uric acid level as a significant predictor of chronic kidney disease: a cohort study with repeated measurements.

BACKGROUND: Cohort studies evaluating increased serum uric acid (SUA) level as a chronic kidney disease (CKD) risk factor have yielded variable results. We aimed to assess the association between the pattern of longitudinal changes in SUA and incident CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)]. METHODS: A population-based cohort study was conducted on 3,605 participants who were followed prospectively for a mean of 5.18 years. The longitudinal changes in SUA were categorized into three subgroups: persistently low, fluctuated (reduced or elevated), and persistently high. The primary outcome of interest was the development of CKD at a follow-up examination. Cox proportional hazards analysis was used to test the hypothesis. RESULTS: After adjustment for potential confounders, participants with fluctuated SUA with progressively elevated level and persistently high SUA level had significantly higher risk of developing CKD compared to subjects with persistently low SUA level: adjusted hazard ratio (95% confidence interval) was 2.05 (1.24-3.38) vs. 1.90 (1.34-2.71). This longitudinal relationship was independent of sex, age, body mass index, and hypertension status. CONCLUSIONS: Longitudinally elevated SUA independently predicts the risk of new-onset CKD.

Predictive value of serum apolipoprotein B/apolipoprotein A-I ratio in metabolic syndrome risk: a Chinese cohort study.

The purpose of this study was to evaluate whether the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio is a promising risk predictor of metabolic syndrome (MetS) and to determine the optimal cut-off value of this ratio in detecting subjects with MetS in a Chinese population. A prospective study was conducted using a representative sample of non-institutionized people in Taiwan. A total of 3,343 participants with mean age (±SD) of 39.86 (±15.61) years old were followed up from 2002 to 2007. The primary outcome was the incidence of MetS. The MetS was defined according to a unified criterion established by several major organizations. There were 462 cases of incident MetS during a mean follow-up period of 5.26 years. A significantly stepwise increase in the incidence of MetS across quartiles of the apoB/apoA-I ratio was noted in both sexes after adjustment for potential confounders (p for trend <0.001). Compared with the lowest quartile of apoB/apoA-I ratio, participants in the highest quartile had a significantly higher risk of MetS in both men [adjusted hazard ratio (HR) = 6.29, 95 % confidence interval (CI) = 2.79-9.13] and women (adjusted HR = 3.82, 95 % CI = 1.06-6.63). Comparisons of receiver operating characteristics curves indicated that the predictive ability of apoB/apoA-I ratio to detect MetS was better than conventional lipid ratio measurements. Furthermore, the optimal cut-off value of apoB/apoA-I ratio for MetS diagnosis was 0.71 in men and 0.56 in women. These results suggest that an elevated apoB/apoA-I ratio might constitute a potentially crucial measure linked to the risk of developing MetS.

Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study.

OBJECTIVE: Despite some epidemiologic research demonstrating a positive relationship between serum uric acid (SUA) levels and the prevalence of metabolic syndrome (MetS), prospective data on SUA as a predictor of MetS incidence are limited. METHODS: The authors examined SUA as a risk marker for incident MetS in a prospective study of 3857 subjects who were free of MetS at baseline recruitment. Hyperuricemia was defined as SUA ≥7.7 mg/dL for men and ≥6.6 mg/dL for women. The MetS was defined according to a unified criteria set by several major organizations. RESULTS: During a mean follow-up of 5.41 years, 476 participants developed MetS. A significantly stepwise increase in the incidence of MetS across tertiles of SUA was observed in the whole group (p for trend <0.001). Among women, this association was more robust than in men. After adjustment for age, variations of blood pressure, triglycerides, HDL-C, glucose, and waist circumference, females in the middle and upper tertiles of SUA had significantly higher risk of developing MetS when compared with subjects in the lowest tertile [adjusted-HR (95% CI) was 1.67 (1.12-2.49) and 3.18 (2.20-4.60), respectively; p for trend <0.001]. Overall, hyperuricemia was a significantly independent risk determinant for MetS in women, but it was a non-significant factor for MetS mediating waist circumference and serum triglycerides in men. CONCLUSION: SUA concentration is more closely associated with MetS in females than in males. Future investigations are needed to explore the underlying mechanisms involved in the sex-related association between SUA concentration and MetS risk.

Dietary intake of vitamin B(6) and risk of breast cancer in Taiwanese women.

BACKGROUND: B vitamins, including vitamin B(6), are coenzymes that are important for DNA integrity and stability. Deficiencies in B vitamins may promote tumor carcinogenesis. METHODS: We examined the association of dietary vitamin B(6) intake with overall breast cancer risk and breast cancers stratified by hormone receptor status. This case-control study included 391 breast cancer cases and 782 control subjects enrolled at the Tri-Service General Hospital in Taipei, Taiwan. Energy-adjusted intake of vitamin B(6) was derived from a food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: As compared with women in the lowest tertile, the multivariate-adjusted ORs for breast cancer among women in the second and highest tertiles of vitamin B(6) intake were 0.78 (95% CI, 0.64-2.52) and 0.64 (0.26-0.92), respectively. In addition, higher vitamin B(6) intake was associated with a significantly lower risk of developing ER-negative breast tumors. CONCLUSIONS: Our findings suggest that higher intake of vitamin B(6) is associated with a reduction in breast cancer risk, particularly ER-negative tumors.

Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case-control study in Taiwan.

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5'-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11-2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89-8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ's effects should be pursued in future investigations.

Adipocytokine resistin and breast cancer risk.

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.

Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study.

Epidemiological observations suggest that insulin-like growth factor-I (IGF-I), a potent mitogenic and anti-apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF-I family. A case-control study was conducted to assess the role of IGF-I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF-I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full-term pregnancy on the risk of breast cancer. Questionnaire information and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2006. Plasma levels of IGF-I and IGFBP-3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case-control data indicate that breast cancer risk related to IGF-I differs according to menopausal status. High circulating levels of IGF-I increased risk of pre- but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01-3.44). Furthermore, elevated IGF-I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen-positive cases (adjusted OR, 2.42, 95% CI, 1.33-4.38). These results suggest that the joint effect of IGF-I and estrogens may provide novel methods of breast cancer risk reduction among women.