The ability of the SCORE high-risk model to predict 10-year cardiovascular disease mortality in Norway.

AIMS: To evaluate the predictive accuracy of the Systematic Coronary Risk Evaluation (SCORE) project high-risk function in Norway. METHODS AND RESULTS: We included 57 229 individuals screened in 1985-1992 from two population-based surveys in Norway (age groups 40-49, 50-59, and 60-69 years). The data have been linked to the Norwegian Cause of Death Registry. The SCORE high-risk algorithm for the prediction of 10-year cardiovascular disease (CVD) mortality was applied, and the risk factors entered into the model were age, sex, total cholesterol, systolic blood pressure, and smoking (yes/no). The number of expected events estimated by the SCORE model (E) was compared with the observed numbers (O). The SCORE low-risk algorithm was studied for comparison. In men, the observed number of CVD deaths was 718, compared with 1464 estimated by the SCORE high-risk function (O/E ratios 0.53, 0.53 and 0.45, for age groups 40-49, 50-59 and 60-69, respectively). In women, the observed and expected numbers were 226 and 547. The O/E ratios decreased with age (ratios 0.60, 0.45 and 0.37, respectively), i.e. the overestimation increased with age. The low-risk function predicted reasonably well for men (ratios 0.85, 0.92 and 0.79, respectively), whereas an overestimation was found for women aged 50-59 and 60-69 years (ratios 0.69 and 0.56, respectively). CONCLUSION: The SCORE high-risk model overestimated the number of CVD deaths in Norway. Before implementation in clinical practice, proper adjustments to national levels are required.     

HIV related and non-HIV related mortality before and after the introduction of highly active antiretroviral therapy (HAART) in Norway compared to the general population

The objective of the study was to compare the mortality in HIV infected individuals to the general population, and to explore the relative contribution of HIV to mortality before and after the introduction of highly active antiretroviral therapy (HAART). All HIV patients attending Ullev?l University Hospital, Oslo, Norway before (cohort 1) and after (cohort 2) the introduction of HAART were included. Causes of deaths were classified as HIV related or not. Mortality in the Norwegian general population was standardized according to the distribution of age and gender in our cohorts. Ratios between mortality in our cohorts and the standardized mortality were calculated. The risk ratio (RR) for 5-y mortality compared to the general population was 22.6 (95% confidence interval (CI), 19.5-26.4) in cohort 1 (n = 782), and 3.96 (95% CI 2.25-6.97) in cohort 2 (n = 398). The non-HIV related mortality RR was 4.42 (95% CI 3.18-6.13) in cohort1 and 0.89 (95% CI 0.29-2.76) in cohort 2. Higher age and low CD4 cell count were associated with increased mortality. Thus, in the HAART era the mortality in HIV patients was reduced by 80%. However, the mortality in the HAART era was still 4 times higher than in the general population.     

The JAK2 V617F somatic mutation, mortality and cancer risk in the general population

JAK2 V617F is present in the majority of patients with myeloproliferative cancer; however, its prevalence and clinical significance in the general population is unknown. We screened for presence of the mutation in 10,507 participants from the Copenhagen City Heart Study with up to 17.6 years of follow up. Prevalence of the mutation was 0.2% (n=18). All 18 mutation positives died during follow up corresponding to a multifactorially adjusted hazard ratio for early death of 3.0 (95%CI:1.9-4.9). Corresponding hazard ratios for men versus women and 1-year age increases were 1.4 (1.1-1.9) and 1.1 (1.1-1.1). Multifactorially adjusted hazard ratios for any cancer, hematologic cancer and myeloproliferative cancer were 3.7 (1.7-8.0), 58 (13-261) and 161 (12-2,197), respectively. Corresponding hazard ratios were 1.2 (0.8-2.0), 2.3 (0.2-25), 1.3 (0.3-5.4) for men versus women, and 1.0 (1.0-1.1), 1.1 (0.9-1.2), 0.9 (0.8-1.1) for 1-year age increases. In the general population, JAK2 V617F is associated with increased morbidity and mortality, although only present in 18 of 10,507 (0.2%).     

Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population

Background: With transfusions and chelation therapy, the prognosis for transfusion‐dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival. Design and methods: In this historical prospective study, we present survival, causes of death and mortality ratios compared to the general population in 1044 Greek patients with transfusion‐dependent beta thalassaemia. Results: At the age of 50 years, the overall survival was 65.0%, while the cardiac death–free survival was 77%. Birth cohort had a significant effect on survival (P < 0.001) with a negative trend towards past decades. The standardised mortality ratio (standardised for sex and ages 20–40 years) compared to the general population improved significantly from 28.9 in 1990–1999 to 13.5 in 2000–2008, while the standardised cardiac mortality ratio reduced from 322.9 to 106.6, respectively. Conclusions: Survival in thalassaemia has dramatically improved over the last twenty years but mortality remains significantly increased, compared to the general population.     

Prolongation of the QTc interval in HIV-infected individuals compared to the general population

Objectives

Prolonged QT interval is associated with arrhythmias and sudden death. An increased prevalence of QT interval prolongation in human immunodeficiency virus-infected (HIV) subjects was previously described. The impact of different medications and HIV infection itself on the QT interval is rarely investigated in large HIV+ cohorts.

Methods

We compared QT interval measurement in 496 HIV(+) patients of the HIV-HEART study (HIVH) and 992 sex- and age-matched controls of the population-based German Heinz Nixdorf Recall study (HNR). QT corrected for heart rate (QTc) >440 ms in male and >460 ms in female was considered pathological. We analysed the impact of HIV status and HIV medication on QTc prolongation in the HIVH subjects.

Results

We observed longer QTc in HIVH subjects compared with HNR controls: 424.1 ms ± 23.3 vs. 411.3 ± 15.3 ms for male and 435.5 ms ± 19.6 vs. 416.4 ms ± 17.3 for female subjects (p < 0.0001 for both sexes). Adjusting for QT prolonging medication the mean differences in QTc between the two studies remained significant with 12.6 ms (95% CI 10.5–14.8; p value <0.0001) for male and 19.3 ms (95% CI 14.5–24.2; p value <0.0001) for female subjects. Prolongation of QTc was pathologic in 22.8 vs. 3.9% of HIV(+) and non-infected males and in 12.1 vs. 1.8% of the females [OR of 7.9 (5.0–12.6) and OR of 6.7 (1.8–24.2), respectively]. Smoking behaviour was an independent factor to lengthen QTc in HIV(+) patients. Diabetes mellitus was not a risk factor itself, but might be associated with medication which was associated with LQT. We could not observe any influence of the HIV status, ART, or any co-medication on the QTc.

Conclusions

Our study showed that HIV(+) patients had significantly longer QTc intervals compared to the general population. The number of patients with pathologic QTc prolongation was significantly increased in HIV(+) population.

     

The recent reduction in mortality from bleeding oesophageal varices is primarily observed from Days 1 to 5

Background: Several new treatments of bleeding oesophageal varices (BOV) have been introduced during the last 25 years; among these are vasoactive drugs, improved endoscopic techniques and prophylactic antibiotics. Aims: The aim was to compare clinical outcomes based on Baveno IV criteria in two patient‐cohorts (1983–1987, n=56 and 2000–2007, n=111) with respect to control of bleeding, rebleeding and mortality after a first episode of BOV. Further, we wanted to assess whether an eventual reduction in bleeding‐related mortality occurred within the first 5 days or between Days 6 and 42 after the bleeding episode. Methods: Data from medical records were collected, according to the Baveno IV criteria, on key events: type of treatment, failure to control bleeding, failure to prevent rebleeding, 5‐day and 6‐week mortality. Results: Six‐week mortality decreased from 30.4 to 17.1% [odds ratio (OR) 0.44; 0.21–0.95] with a reduction in 5‐day mortality from 17.9 to 6.3% (OR 0.31; 0.11–0.86). A non‐significant reduction was seen in the 5‐day failure rate to control bleeding from 35.7 to 26.1%. Mortality and failure to prevent rebleeding Days 6–42 decreased from 15.2 to 11.5% (NS) and 22.2 to 10.7% (NS) respectively. Mean length of hospital stay decreased from 14.6 ± 12.5 to 9.1 ± 9.0 days (P<0.01) and mean number of cumulated blood transfusions within the first 5 days decreased from 5.0 ± 4.8 to 3.6 ± 3.9 (P=0.05). Conclusions: In this retrospective study on individual patient records, we observed a decrease in mortality from BOV over the last 20 years, which seems mainly owing to a reduction in 5‐day mortality; mortality at Days 6–42 remained unaffected.     

Alcohol consumption patterns and risk factors among childhood cancer survivors compared to siblings and general population peers

AIMS: This study describes alcohol consumption among adult survivors of pediatric cancer compared to sibling controls and a national sample of healthy peers. Risk factors for heavy drinking among survivors are described. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data were utilized from the Childhood Cancer Survivor Study including adult survivors of pediatric cancer (n = 10 398) and a sibling cohort (n = 3034). Comparison data were drawn from the National Alcohol Survey (n = 4774). MEASUREMENT: Alcohol consumption, demographic, cancer diagnosis, treatment and psychosocial factors were measured. FINDINGS: Compared to peers, survivors were slightly less likely to be risky [adjusted odds ratio (ORadj) = 0.9; confidence interval (CI) 0.8-1.0] and heavy drinkers (ORadj = 0.8; CI 0.7-0.9) and more likely to be current drinkers. Compared to siblings, survivors were less likely to be current, risky and heavy drinkers. Risk factors for survivors' heavy drinking included being age 18-21 years (ORadj = 2.0; 95% CI 1.5-2.6), male (ORadj = 2.1; 95% CI 1.8-2.6), having high school education or less (ORadj = 3.4; 95% CI 2.7-4.4) and drinking initiation before age 14 (ORadj = 6.9; 95% CI 4.4-10.8). Among survivors, symptoms of depression, anxiety or somatization, fair or poor self-assessed health, activity limitations and anxiety about cancer were associated with heavy drinking. Cognitively compromising treatment, brain tumors and older age at diagnosis were protective. CONCLUSIONS: Adult survivors of childhood cancer show only a modest reduction in alcohol consumption compared to peers despite their more vulnerable health status. Distress and poorer health are associated with survivor heavy drinking. Screening for alcohol consumption should be instituted in long-term follow-up care and interventions among survivors and siblings should be established to reduce risk for early drinking.     

Changes in serum uric acid and the risk of cardiovascular disease and all-cause mortality in the general population

Background and aimLongitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear.Methods and resultsA total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02–1.29) and 1.20 (1.06–1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%.ConclusionsChanges in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk.     

Genetic risk of fatty liver disease and mortality in the general population: A Mendelian randomization study

Background & Aims

Fatty liver disease has been associated with higher all-cause as well as liver-related, ischemic heart disease (IHD)-related and extrahepatic cancer-related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality.

Methods

We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver-related mortality.

Results

During a median follow-up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all-cause (1.26-fold), liver-related (9-fold), and extrahepatic cancer-related (1.25-fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver-related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3-fold and 6-fold, respectively, higher liver-related mortality than non-carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all-cause, IHD-related, or extrahepatic cancer-related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver-related mortality.

Conclusions

Human genetic data support that fatty liver disease is a causal driver of liver-related mortality.     

The widening mortality gap between rheumatoid arthritis patients and the general population

OBJECTIVE: Overall mortality rates in the general US population have declined substantially over the last 4-5 decades, but it is unclear whether patients with rheumatoid arthritis (RA) have experienced the same improvements in survival. The purpose of this study was to determine the mortality trends among RA patients compared with those in the general population. METHODS: A population-based incidence cohort of RA patients was assembled, comprising all residents of Rochester, Minnesota ages > or = 18 years in whom RA was first diagnosed (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1987 criteria) between 1955 and 1995 and all residents of Olmsted County, Minnesota in whom RA was first diagnosed between 1995 and 2000. The patients were followed up longitudinally through their complete (inpatient and outpatient) medical records until death or January 1, 2007. Expected mortality was estimated from the National Center for Health Statistics life tables on the white population in Minnesota, using person-year methods. Poisson regression was used to model the observed mortality rates, adjusting for age, sex, and disease duration. RESULTS: A cohort of 822 RA patients (72% women, mean age at RA incidence 58 years) was followed up for a median of 11.7 years, during which 445 of the RA patients died. Between 1965 and 2005, the mortality rates across the calendar years for female and male RA patients were relatively constant at 2.4 and 2.5 per 100 person-years, respectively. In contrast, the expected mortality rate in the Minnesota white population decreased substantially over the same time period in both sexes. Mortality in the female general population declined from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000. Mortality in the male general population decreased from 1.2 per 100 person-years in 1965 to 0.3 per 100 person-years in 2000. Therefore, the difference between the observed and expected mortality rates increased in more recent years, resulting in a widening of the mortality gap. CONCLUSION: Our findings show that RA patients have not experienced improvements in survival over the past 4 decades, despite dramatic improvements in the overall rates of mortality in the general US population. Further research into the causes of the widening gap in mortality between RA patients and the general population, and the influence of current therapeutic strategies on mortality, is needed in order to develop strategies to reduce the excess mortality observed in RA patients.     

Dehydroepiandrosterone sulfate, diseases and mortality in a general aged population.

Dehydroepiandrosterone sulfate (DHEAS) was measured in a five-year follow-up study of random persons of three age cohorts (75-, 80-, and 85-years, N = 571) in order to investigate its associations with clinical diseases and their risk indicators, as well as its prognostic significance in old age. DHEAS was higher in men (3.1 mumol/L) than in women (1.9 mumol/L) in the 75-year age group. It decreased in men up 85 years. Compared to healthy men, DHEAS was lower in men with a history of or manifest vascular diseases, presence of dementia, diabetes mellitus, malignancies and musculoskeletal disorders, but was similar in all these disease groups. No differences were found in women. DHEAS did not relate to cardioechographic findings, cardiovascular risk factors or predictors of impaired survival prognosis. After controlling for age, DHEAS tended to be lower in the non-surviving than in the surviving men (2.28 mumol/L vs 2.65 mumol/L, p = 0.065). After controlling for disease, DHEAS did not predict increased risk of all-cause or cardiovascular mortality during the 5-year follow-up. In this study, gender differences in DHEAS persisted up to the age of 75 years. Low plasma DHEAS appears to be a secondary phenomenon rather than a specific risk indicator of common diseases in old age.