Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis.

BACKGROUND: Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. OBJECTIVES: We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD). METHODS: We investigated the association between milk intake, LCT-13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from five published Northern European population studies. RESULTS: In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99-1.01). The per T-allele milk intake was 0.58 (0.49-0.68) glasses per week, but HR was 1.01 (0.94-1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61-1.21; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 17%) g cm-2 for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC. CONCLUSION: Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.

Chylomicronemia risk factors ranked by importance for the individual and community in 108 711 women and men.

BACKGROUND: Hypertriglyceridemia prevalence is increasing as more individuals become obese, and chylomicronemia risk factors for the individual and community have not been described previously. OBJECTIVE: To describe chylomicronemia risk factors in the general population for individuals and community. METHODS: A total of 108 711 individuals from the Copenhagen General Population Study were grouped as unlikely chylomicronemia (nonfasting triglycerides <2 mmol L-1 (177 mg dL-1 )), possible chylomicronemia (2-4.99 mmol L-1 (177-442 mg dL-1 )), probable chylomicronemia (5-9.99 mmol L-1 (443-885 mg dL-1 )) and definite chylomicronemia (≥10 mmol L-1 (≥ 886 mg dL-1 )). Relative risk (RR) from Poisson regression ranked dichotomized chylomicronemia risk factors for individuals, and population attributable fractions (PAF) for the community: type 2 diabetes, alcohol intake, obesity, fat intake, hypothyroidism, kidney function, education, sedentary lifestyle, menopause and hormone replacement (women). RESULTS: For women and men, chylomicronemia was unlikely in 81% and 64%, possible in 18% and 33%, probable in 1% and 3% and definite in 0.03% and 0.14%, respectively. For the individual, the three top-ranked risk factors for probable/definite versus unlikely chylomicronemia in women were type 2 diabetes (RR: 4.21; 95% confidence interval: 3.30-5.36), menopause (RR: 3.74; 2.62-5.36) and obesity (RR: 3.44; 2.81-4.21). Corresponding top-ranked risk factors in men were obesity (RR: 3.86; 3.46-4.30), type 2 diabetes (RR: 1.88; 1.61-2.19) and reduced kidney function (RR: 1.86; 1.48-2.34). For the community, top-ranked risk factors in women were menopause (PAF: 63%), obesity (PAF: 29%) and type 2 diabetes (PAF: 15%). Corresponding top-ranked risk factors in men were obesity (PAF: 29%), type 2 diabetes (PAF: 6.4%) and sedentary lifestyle (PAF: 6.0%). CONCLUSIONS: Obesity and type 2 diabetes were the most important modifiable chylomicronemia risk factors in women and men, both for the individual and community. This could influence chylomicronemia prevention and help design randomized trials aimed at reducing triglycerides.

Filaggrin loss-of-function mutations as risk factors for ischemic stroke in the general population.

Essentials FLG mutations cause atopic dermatitis, previously found to be associated with ischemic stroke. Association between FLG mutations and ischemic stroke was examined in 97 174 Danish individuals. FLG mutations were associated with increased ischemic stroke risk in the general population. The association was most pronounced in younger individuals, and in current and former smokers. SUMMARY: Background Heritability studies have shown a considerable genetic component to ischemic stroke risk; however, much is unknown as to which genes are responsible. Also, previous studies have found an association between atopic dermatitis and increased ischemic stroke risk. Objective To test the hypothesis that FLG loss-of-function mutations, known to be associated with atopic dermatitis, were also associated with ischemic stroke. Methods A total of 97 174 individuals, with 3597 cases of ischemic stroke, from the Copenhagen General Population Study, the Copenhagen City Heart Study and the Copenhagen Carotid Stroke Study were genotyped for the two most common filaggrin mutations, FLG R501X and FLG 2282del4. Results FLG mutation carriers had an odds ratio for ischemic stroke of 1.15 (95% confidence interval [CI], 1.02-1.30) compared with non-carriers. Risk of ischemic stroke for FLG mutation carriers was higher among individuals aged < 50 years, with an odds ratio of 1.72 (1.11-2.67), compared with non-carriers. When stratified for smoking, ischemic stroke risk was primarily seen in current and former smokers, with an odds ratio of 1.25 (1.08-1.44). FLG mutations were not associated with conventional cardiovascular risk factors except for slightly more pack-years smoked among mutation carriers, but were associated with increased risk of self-reported eczema, with an odds ratio of 1.42 (1.32-1.52). Finally, self-reported eczema was associated with increased ischemic stroke risk, with an age and sex adjusted hazard ratio of 1.24 (1.01-1.52); however, the association was not statistically significant after multifactorial adjustment. Conclusion In this study of 97 174 individuals from the Danish general population, FLG loss-of-function mutations were associated with increased ischemic stroke risk; however, residual confounding is a possibility.

Disminución de triglicéridos sin ayuno y reducción de mortalidad por cualquier causa: un estudio de randomización mendeliana / Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study

Antecedentes: El aumento de los triglicéridos plasmáticos sin ayuno, marcador del aumento de colesterol en lipoproteínas remanentes, es un importante factor de riesgo para enfermedad cardiovascular, pero se desconoce si la reducción en las concentraciones de triglicéridos, sobre una base genética, a lo largo de toda la vida en última instancia conduce a una menor mortalidad por cualquier causa. Pusimos a prueba esta hipótesis. Métodos: Estudiando individuos del Copenhagen City Heart Study en un diseño de randomización mendeliana, en primer lugar estudiamos si las menores concentraciones de triglicéridos sin ayuno se asociaron con una reducción de mortalidad por cualquier causa en un análisis observacional (n=13.957); segundo, si variantes genéticas en la enzima hidrolizante de triglicéridos lipoproteína lipasa, que resultan en reducción de los triglicéridos plasmáticos sin ayuno y del colesterol de remanentes, se asociaron con una reducción de mortalidad por cualquier causa (n=10.208). Resultados...

Background: Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Methods: Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). Results...

In situ and invasive squamous cell carcinoma of the vulva in Denmark 1978-2007-a nationwide population-based study.

OBJECTIVE: To determine the incidence of vulvar carcinoma in situ (CIS) and cancer of squamous cell (SC) origin in Denmark in the period 1978-2007. METHODS: Using the nationwide Danish Cancer Registry, we identified 980 women diagnosed with vulvar CIS 1978-2003 (67.8% were SC) and 2455 women diagnosed with vulvar cancer 1978-2007 (76.0% were SC). Analysis was restricted to vulvar CIS and cancer of SC origin. We assessed age-specific incidence rates, age-standardized incidence rates, and distribution of stage at diagnosis. Poisson regression analysis was used to estimate the average annual percentage change. RESULTS: During the study period the age-standardized incidence rate of vulvar SC CIS increased by 1.97% per year (95% CI: 0.99% to 2.96%) with a tendency toward a steeper increase among women younger than 50 years. The age-standardized incidence rate of vulvar SC cancer showed a stable or slightly increasing pattern. However, among women below 60 years of age a significantly increasing trend was observed (1.60% per year; 95% CI: 0.50% to 2.71%). The distribution in the extent of vulvar SC cancer at diagnosis showed a tendency toward a higher proportion being diagnosed with localized disease in the more recent calendar years. CONCLUSIONS: The incidence rates of vulvar SC CIS and vulvar SC cancer among women below the age of 60 years have increased since 1978. Human papillomavirus (HPV) could explain the increase and thus, the recent introduction of HPV vaccination may in the future result in a notable reduction of vulvar malignancies.