Elisabeth Wreford Andersen

Risk of cardiovascular disease in family members of young sudden cardiac death victims

AIMS Descriptive and genetic studies suggest that relatives of sudden cardiac death (SCD) victims have an increased risk of several cardiovascular diseases (CVDs). Given the severe consequences of undiagnosed CVD and the availability of effective treatment, the potential for prevention in this group is enormous if they do have an increased CVD risk. This nationwide prospective population-based cohort study described the risk of CVDs in relatives of young SCD victims, compared with the general population. METHODS AND RESULTS All SCD victims aged 1-35 years in Denmark, 2000-2006, were identified (n = 470), along with their first- and second-degree relatives (n = 3073). We compared the incidence of CVD in those relatives with that in the background population using standardized incidence ratios (SIRs). The observed number of CVDs over 11 years of follow-up was 292, compared with 219 expected based on national rates [SIR 1.33, 95% confidence interval (CI) 1.19-1.50]. Risks varied significantly with age; the SIR for those <35 years was 3.53 (95% CI 2.65-4.69), compared with SIRs of 1.59 (95% CI 1.35-1.89) and 0.91 (95% CI 0.75-1.10) for those aged 35-60 years or >60 years, respectively (P(homogeneity) < 0.0001). For first-degree relatives <35 years, SIRs for ischaemic heart disease, cardiomyopathy, and ventricular arrhythmia were 5.99 (95% CI 1.95-0.13.98), 17.91 (95% CI 4.88-45.87), and 19.15 (95% CI 7.70-39.45), respectively. CONCLUSION CVDs co-aggregated significantly with SCD in families, with young first-degree relatives at greatest risk. Results clearly indicate that family members of young SCD victims should be offered comprehensive and systematic screening, with focus on the youngest relatives.

Vitamin D Status during Pregnancy and the Risk of Subsequent Postpartum Depression: A Case-Control Study

Epidemiological studies have provided evidence of an association between vitamin D insufficiency and depression and other mood disorders, and a role for vitamin D in various brain functions has been suggested. We hypothesized that low vitamin D status during pregnancy might increase the risk of postpartum depression (PPD). The objective of the study was thus to determine whether low vitamin D status during pregnancy was associated with postpartum depression. In a case-control study nested in the Danish National Birth Cohort, we measured late pregnancy serum concentrations of 25[OH]D3 in 605 women with PPD and 875 controls. Odds ratios [OR) for PPD were calculated for six levels of 25[OH]D3. Overall, we found no association between vitamin D concentrations and risk of PPD (p = 0.08). Compared with women with vitamin D concentrations between 50 and 79 nmol/L, the adjusted odds ratios for PPD were 1.35 (95% CI: 0.64; 2.85), 0.83 (CI: 0.50; 1.39) and 1.13 (CI: 0.84; 1.51) among women with vitamin D concentrations < 15 nmol/L, 15–24 nmol/L and 25–49 nmol/L, respectively, and 1.53 (CI: 1.04; 2.26) and 1.89 (CI: 1.06; 3.37) among women with vitamin D concentrations of 80–99 nmol/L and ≥ 100 nmol/L, respectively. In an additional analysis among women with sufficient vitamin D (≥ 50 nmol/L), we observed a significant positive association between vitamin D concentrations and PPD. Our results did not support an association between low maternal vitamin D concentrations during pregnancy and risk of PPD. Instead, an increased risk of PPD was found among women with the highest vitamin D concentrations.

Pregnancy loss and later risk of atherosclerotic disease.

Background— Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension. Methods and Results— Among women pregnant at least once between 1977 and 2008, we identified a cohort of women with miscarriages, stillbirths, or live singleton births. These women were followed from the end of pregnancy for incident myocardial infarction, cerebral infarction, and renovascular hypertension. Using Poisson regression, we estimated incidence rate ratios for each of the outcomes by history of miscarriage and stillbirth. Among 1 031 279 women followed for >15 928 900 person-years, we identified 27 98 myocardial infarctions, 40 53 cerebral infarctions, and 1269 instances of renovascular hypertension. Women with stillbirths had 2.69 (95% confidence interval, 2.06–3.50), 1.74 (1.32–2.28), and 2.42 (1.59–3.69) times the rates of myocardial infarction, cerebral infarction, and renovascular hypertension, respectively, as women with no stillbirths. Compared with women with no miscarriages, women with miscarriages had 1.13 (1.03–1.24), 1.16 (1.07–1.25), and 1.20 (1.05–1.38) times the rates of these same outcomes, respectively; these associations were dose dependent, with each additional miscarriage increasing the rates of myocardial and cerebral infarction and renovascular hypertension by 9% (3% to 16%), 13% (7% to 19%), and 19% (9% to 30%), respectively. Associations were strongest in younger women (<35 years). Conclusions— Pregnancy losses were associated with subsequent risks of myocardial infarction, cerebral infarction, and renovascular hypertension, consistent with either shared etiology or the initiation of pathological processes by a pregnancy loss leading to atherosclerosis.

Breast cancer in women using digoxin: tumor characteristics and relapse risk

IntroductionDigoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer.MethodsIncident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models.ResultsAt diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen.ConclusionsBreast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis.

Risk of Retinal Detachment After Pediatric Cataract Surgery

PURPOSE To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment. METHODS We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark, excluding cataract cases caused by trauma, or acquired systemic or acquired ocular pathology, and cases with ocular anomalies associated with the development of retinal detachment. Cases of cataract were ascertained from the mandatory Danish National Patient Register, and information on retinal detachment was based on medical chart review. RESULTS Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3%-11%) among cataract patients. In otherwise normal children having isolated cataract, the risk was 3% (95% CI: 0%-7%). A significantly higher risk of developing retinal detachment was found in children with mental retardation (23% [95% CI: 9%-35%]) or in cataract cases with other ocular or systemic anomalies (16% [95% CI: 6%-24%]). CONCLUSIONS The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other ocular or systemic diseases.

Spironolactone use and the risk of breast and gynecologic cancers

Spironolactone, an aldosterone-antagonist, is associated with gynecomastia. Digoxin, which can also cause gynecomastia, has been associated with increased incidence of breast and uterus cancers. We therefore postulated that spironolactone use might also increase these cancer risks. Using a nationwide prescription drug registry between 1995 and 2010, we identified use of spironolactone in a cohort of Danish women (≥20 years old). In users and non-users, incidence rate ratios adjusted by age group and calendar-year examined risk of breast and uterus cancers, both estrogen-sensitive, and ovary and cervix cancers, both relatively estrogen-insensitive. As an added control exposure, risk ratios in women who used another diuretic, furosemide, were examined by the same approach. Among 2.3 million women (28.5 million person-years), risks of breast, uterus, ovary, and cervix cancers were generally increased about 10-30% in both spironolactone and furosemide users. In the first year of drug exposure, incidences were increased, especially for ovary cancers. However, incidence increases in the first year of use were not specific for estrogen-sensitive cancers, occurred with both spironolactone and furosemide, and were driven by exposures immediately prior to diagnosis. For drug exposure ≥1 years before cancer diagnosis, incidences of these cancers were not significantly increased. We conclude that associations observed with first use in the year immediately before cancer diagnosis were driven by reverse causality, i.e., because of treatment for symptoms related to the incipient cancer. With respect to breast, uterus, ovarian and cervical cancer, there is no evidence of increased risk with spironolactone or furosemide use.