Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Cardiovascular risk factor profiles and their social gradient from adolescence to age 74 in a Swiss region.

BACKGROUND: Few European studies have investigated how cardiovascular risk factors (CRF) in adults relate to those observed in younger generations. OBJECTIVE: To explore this issue in a Swiss region using two population health surveys of 3636 adolescents ages 9-19 years and 3299 adults ages 25-74 years. METHODS: Age patterns of continuous CRF were estimated by robust locally weighted regression and those of high-risk groups were calculated using adult criteria with appropriate adjustment for children. RESULTS: Gender differences in height, weight, blood pressure, and HDL cholesterol observed in adults were found to emerge in adolescents. Overweight, affecting 10-12% of adolescents, was increasing steeply in young adults (three times among males and twice among females) in parallel with inactivity. Median age at smoking initiation was decreasing rapidly from 18 to 20 years in young adults to 15 in adolescents. A statistically significant social gradient in disfavor of the lower education level was observed for overweight in all age groups of women above 16 (odds ratios (ORs) 2.4 to 3.3, P < 0.01), for inactivity in adult males (ORs 1.6 to 2.0, P < 0.05), and for regular smoking in older adolescents (OR 1.9 for males, 2.7 for females, P < 0.005), but not for elevated blood pressure. CONCLUSION: Discontinuities in the cross-sectional age patterns of CRF indicated the emergence of a social gradient and the need for preventive actions against the early adoption of persistent unhealthy behaviors, to which low-educated girls and women are particularly exposed.

Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

OBJECTIVE: To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure >/= 140/90 mmHg and/or total serum cholesterol >/= 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk >/= 10% or >/= 20%).METHODS: CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (>/= 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication.FINDINGS: A total CV risk of >/= 10% and >/= 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100 000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted.CONCLUSION: Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.

Early-onset Crohn's disease is a risk factor for smaller final height

OBJECTIVES: Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS: Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS: Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION: Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Risk factor profile and management of cerebrovascular patients in the REACH Registry.

BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.

Intergenerational differences in cardiovascular risk factor levels in Switzerland

Background: There is little information regarding cardiovascular risk factor (CV RF) trends in Switzerland. We aimed at assessing generation differences in CV RFs by comparing CV RFs levels within selected age groups separated by a 20 year time lag. Design: Two population-based surveys. Methods: Data from the Monica (1984-1986) and Colaus (2004-2006) surveys were used. Analyses were stratified by sex and age groups (35-44, 45-54, 55-64 and 65-75 years). Results: No changes were found for BMI levels and status between surveys: in men, 26}3, 26}3, 27}4 and 27}4 kg/m2 for age groups 35-44, 45-54, 55-64 and 65-74, respectively, in MONICA, vs. 26}4, 26}4, 27}4 and 28}4 kg/m2 in COLAUS, p=NS, in women: 24}4, 26}4, 26}4 and 26}5 kg/m2 in MONICA, vs. 24}5, 25}5, 26}5 and 26}5 kg/m2 in COLAUS, p=NS. Similar results were found after adjusting for education. Smoking prevalence increased in men: 28, 30, 22 and 15% for age groups 35-44, 45-54, 55-64 and 65-74, respectively, in MONICA, vs. 35, 29, 28 and 21% in COLAUS. In women, changes differed according to age: 39, 26, 16 and 18%, in MONICA vs. 28, 30, 22 and 15% in COLAUS. Blood pressure decreased in the younger age groups and remained constant in the older ones: in men, systolic blood pressure was 129}15, 133}16, 138}18 and 143}21 mm Hg in MONICA, vs. 125}12, 129}15, 137}16 and 144}19 mm Hg in COLAUS, p<0.01. Similar findings were obtained after adjusting for education. Prevalence of hypertension increased, due to an increase in the prevalence of treated subjects, in men : 4, 8, 16 and 19% for age groups 35-44, 45-54, 55-64 and 65-74, respectively, in MONICA, vs. 5, 14, 31 and 46% in COLAUS, p<0.05; in women: 2, 10, 16, and 24% in MONICA, vs. 4, 12, 24, and 34% in COLAUS, p<0.05. This increase was stronger in men: 14, 17, 23 and 31% for age groups 35-44, 45-54, 55-64 and 65-74, respectively, in MONICA vs. 10, 21, 41 and 55% in COLAUS, p<0.01 and smaller in women: 6, 15, 24 and 44% in MONICA vs. 6, 16, 30 and 42% in COLAUS, p=NS. Similar findings were obtained after adjusting for education. Conclusion: With the exception of BMI, the newer Swiss generations appear to have a worse CV profile than the older generations. This is especially true regarding smoking and hypertension.

Residual venous obstruction, alone and in combination with D-dimer, as a risk factor for recurrence after anticoagulation withdrawal following a first idiopathic deep vein thrombosis in the prolong study.

OBJECTIVE: This study aims to assess the predictive value of residual venous obstruction (RVO) for recurrent venous thrombo-embolism (VTE) in a study using D-dimer to predict outcome. DESIGN: This is a multicentre randomised open-label study. METHODS: Patients with a first episode of idiopathic VTE were enrolled on the day of anticoagulation discontinuation when RVO was determined by compression ultrasonography in those with proximal deep vein thrombosis (DVT) of the lower limbs. D-dimer was measured after 1 month. Patients with normal D-dimer did not resume anticoagulation while patients with abnormal D-dimer were randomised to resume anticoagulation or not. The primary outcome measure was recurrent VTE over an 18-month follow-up. RESULTS: A total of 490 DVT patients were analysed (after excluding 19 for different reasons and 118 for isolated pulmonary embolism (PE)). Recurrent DVT occurred in 19% (19/99) of patients with abnormal D-dimer who did not resume anticoagulation and 10% (31/310) in subjects with normal D-dimer (adjusted hazard ratio: 2.1; p = 0.02). Recurrences were similar in subjects either with (11%, 17/151) or without RVO (13%, 32/246). Recurrent DVT rates were also similar for normal D-dimer, with or without RVO, and for abnormal D-dimer, with or without RVO. CONCLUSIONS: Elevated D-dimer at 1 month after anticoagulation withdrawal is a risk factor for recurrence, while RVO at the time of anticoagulation withdrawal is not.

Health in Iowa Annual Report: Behavioral Risk Factor Surveillance System, 2013

The Iowa Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing telephone survey. It is financially and technically supported by the CDC with further financial support from public and private sources. The BRFSS is designed to collect information on the health conditions, health-related behaviors, attitudes, and awareness of residents age 18 and over. It also monitors the prevalence of these indicators over time. The indicators surveyed are major contributors to illness, disability, and premature death. This report focuses on the data collected during calendar year 2013. Some of the health-related issues discussed are general health status, health care access, cancer screening, tobacco use, alcohol consumption, body weight, physical activity, oral health, diabetes, respiratory conditions, immunizations, and HIV/AIDS awareness.

Health in Iowa Annual Report: Behavioral Risk Factor Surveillance System, 2014

The Iowa Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing telephone survey. It is financially and technically supported by the CDC with further financial support from public and private sources. The BRFSS is designed to collect information on the health conditions, health-related behaviors, attitudes, and awareness of residents age 18 and over. It also monitors the prevalence of these indicators over time. The indicators surveyed are major contributors to illness, disability, and premature death. This report focuses on the data collected during calendar year 2013. Some of the health-related issues discussed are general health status, health care access, cancer screening, tobacco use, alcohol consumption, body weight, physical activity, oral health, diabetes, respiratory conditions, immunizations, and HIV/AIDS awareness.

Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART.

The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count >or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count >or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

Treatment intensification and risk factor control: toward more clinically relevant quality measures.

BACKGROUND: Intensification of pharmacotherapy in persons with poorly controlled chronic conditions has been proposed as a clinically meaningful process measure of quality. OBJECTIVE: To validate measures of treatment intensification by evaluating their associations with subsequent control in hypertension, hyperlipidemia, and diabetes mellitus across 35 medical facility populations in Kaiser Permanente, Northern California. DESIGN: Hierarchical analyses of associations of improvements in facility-level treatment intensification rates from 2001 to 2003 with patient-level risk factor levels at the end of 2003. PATIENTS: Members (515,072 and 626,130; age >20 years) with hypertension, hyperlipidemia, and/or diabetes mellitus in 2001 and 2003, respectively. MEASUREMENTS: Treatment intensification for each risk factor defined as an increase in number of drug classes prescribed, of dosage for at least 1 drug, or switching to a drug from another class within 3 months of observed poor risk factor control. RESULTS: Facility-level improvements in treatment intensification rates between 2001 and 2003 were strongly associated with greater likelihood of being in control at the end of 2003 (P < or = 0.05 for each risk factor) after adjustment for patient- and facility-level covariates. Compared with facility rankings based solely on control, addition of percentages of poorly controlled patients who received treatment intensification changed 2003 rankings substantially: 14%, 51%, and 29% of the facilities changed ranks by 5 or more positions for hypertension, hyperlipidemia, and diabetes, respectively. CONCLUSIONS: Treatment intensification is tightly linked to improved control. Thus, it deserves consideration as a process measure for motivating quality improvement and possibly for measuring clinical performance.