A longitudinal analysis of the risk factors for diabetes and coronary heart disease in the Framingham Offspring Study

BACKGROUND: The recent trends in sedentary life-styles and weight gain are likely to contribute to chronic conditions such as hypertension, diabetes, and cardiovascular diseases. The temporal sequence and pathways underlying these conditions can be modeled using the knowledge from the biomedical and social sciences. METHODS: The Framingham Offspring Study in the U.S. collected information on 5124 subjects at baseline, and 8, 12, 16, and 20 years after the baseline. Dynamic random effects models were estimated for the subjects' weight, LDL and HDL cholesterol, and blood pressure using 4 time observations. Logistic and probit models were estimated for the probability of diabetes and coronary heart disease (CHD) events. RESULTS: The subjects' age, physical activity, alcohol consumption, and cigarettes smoked were important predictors of the risk factors. Moreover, weight and height were found to differentially affect the probabilities of diabetes and CHD events; body weight was positively associated with the risk of diabetes while taller individuals had lower risk of CHD events. CONCLUSION: The results showed the importance of joint modeling of body weight, LDL and HDL cholesterol, and blood pressure that are risk factors for diabetes and CHD events. Lower body weight and LDL concentrations and higher HDL levels achieved via physical exercise are likely to reduce diabetes and CHD events

Mortality Risk Prediction by an Insurance Company and Long-Term Follow-Up of 62,000 Men

Background: Insurance companies use medical information to classify the mortality risk of applicants. Adding genetic tests to this assessment is currently being debated. This debate would be more meaningful, if results of present-day risk prediction were known. Therefore, we compared the predicted with the observed mortality of men who applied for life insurance, and determined the prognostic value of the risk assessment. Methods: Long-term follow-up was available for 62,334 male applicants whose mortality risk was predicted with medical evaluation and they were assigned to five groups with increasing risk from 1 to 5. We calculated all cause standardized mortality ratios relative to the Dutch population and compared groups with Cox's regression. We compared the discriminative ability of risk assessments as indicated by a concordance index (c). Results: In 844,815 person years we observed 3,433 deaths. The standardized mortality relative to the Dutch male population was 0.76 (95 percent confidence interval, 0.73 to 0.78). The standardized mortality ratios ranged from 0.54 in risk group 1 to 2.37 in group 5. A large number of risk factors and diseases were significantly associated with increased mortality. The algorithm of prediction was significantly, but only slightly better than summation of the number of disorders and risk factors (c-index, 0.64 versus 0.60, P,0.001). Conclusions: Men applying for insurance clearly had better survival relative to the general population. Readily available medical evaluation enabled accurate prediction of the mortality risk of large groups, but the deceased men could not have been identified with the applied prediction method

Relative risk for cardiovascular atherosclerotic events after smoking cessation: 6–9 years excess risk in individuals with familial hypercholesterolemia

BACKGROUND: Smoking history is often di- or trichotomized into for example "never, ever or current smoking". However, smoking must be treated as a time-dependent covariate when lifetime data is available. In particular, individuals do not smoke at birth, there is usually a wide variation with respect to smoking history, and smoking cessation must also be considered. METHODS: Therefore we analyzed smoking as a time-dependent risk factor for cardiovascular atherosclerotic events in a cohort of 2400 individuals with familial hypercholesterolemia who were followed from birth until 2004. Excess risk after smoking-cessation was modelled in a Cox regression model with linear and exponential decaying trends. The model with the highest likelihood value was used to estimate the decay of the excess risk of smoking. RESULTS: Atherosclerotic events were observed in 779 patients with familial hypercholesterolemia and 1569 individuals had a smoking history. In the model with the highest likelihood value the risk reduction of smoking after cessation follows a linear pattern with time and it appears to take 6 to 9 years before the excess risk is reduced to zero. The risk of atherosclerotic events due to smoking was estimated as 2.1 (95% confidence interval 1.5; 2.9). CONCLUSION: It was concluded that excess risk due to smoking declined linearly after cessation in at least six to nine years

Measuring hsCRP—An Important Part of a Comprehensive Risk Profile or a Clinically Redundant Practice?

James McCormack and Michael Allan discuss issues and questions surrounding hsCRP measurements in patients

The cumulative effect of core lifestyle behaviours on the prevalence of hypertension and dyslipidemia

Background: Most cardiovascular disease (CVD) occurs in the presence of traditional risk factors, including hypertension and dyslipidemia, and these in turn are influenced by behavioural factors such as diet and lifestyle. Previous research has identified a group at low risk of CVD based on a cluster of inter-related factors: body mass index (BMI) < 25 Kg/m2, moderate exercise, alcohol intake, non-smoking and a favourable dietary pattern. The objective of this study was to determine whether these factors are associated with a reduced prevalence of hypertension and dyslipidemia in an Irish adult population. Methods: The study was a cross-sectional survey of 1018 men and women sampled from 17 general practices. Participants completed health, lifestyle and food frequency questionnaires and provided fasting blood samples for analysis of glucose and insulin. We defined a low risk group based on the following protective factors: BMI <25 kg/m2; waist-hip ratio (WHR) <0.85 for women and <0.90 for men; never smoking status; participants with medium to high levels of physical activity; light alcohol consumption (3.5–7 units of alcohol/week) and a "prudent" diet. Dietary patterns were assessed by cluster analysis. Results: We found strong significant inverse associations between the number of protective factors and systolic blood pressure, diastolic blood pressure and dyslipidemia. The prevalence odds ratio of hypertension in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none, were 1.0, 0.76, 0.68 and 0.34 (trend p < 0.01). The prevalence odds ratio of dyslipidemia in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none were 0.83, 0.98, 0.49 and 0.24 (trend p = 0.001). Conclusion: Our findings of a strong inverse association between low risk behaviours and two of the traditional risk factors for CVD highlight the importance of 'the causes of the causes' and the potential for behaviour modification in CVD prevention at a population level

The association between processes, structures and outcomes of secondary prevention care among VA ischemic heart disease patients

BACKGROUND: Hyperlipidemia and hypertension are well-established risk factors for recurrent cardiovascular events among patients with ischemic heart disease (IHD). Despite national recommendations, concordance with guidelines for LDL cholesterol and blood pressure remains inadequate. The objectives of this study were to 1) determine concordance rates with LDL cholesterol and BP recommendations; and 2) identify patient factors, processes and structures of care associated with guideline concordance among VA IHD patients. METHODS: This was a cross sectional study of veterans with IHD from 8 VA hospitals. Outcomes were concordance with LDL guideline recommendations (LDL<100 mg/dl), and BP recommendations (<140/90 mm Hg). Cumulative logit and hierarchical logistic regression analyses were performed to identify patient factors, processes, and structures of care independently associated with guideline concordance. RESULTS: Of 14,114 veterans with IHD, 55.7% had hypertension, 71.5% had hyperlipidemia, and 41.6% had both conditions. Guideline concordance for LDL and BP were 38.9% and 53.4%, respectively. However, only 21.9% of the patients achieved both LDL <100 mg/dl and BP <140/90 mm Hg. In multivariable analyses, patient factors including older age and the presence of vascular disease were associated with worse guideline concordance. In contrast, diabetes was associated with better guideline concordance. Several process of care variables, including higher number of outpatient visits, higher number of prescribed medications, and a recent cardiac hospitalization were associated with better guideline concordance. Among structures of care, having on-site cardiology was associated with a trend towards better guideline concordance. CONCLUSION: Guideline concordance with secondary prevention measures among IHD patients remains suboptimal. It is hoped that the findings of this study can serve as an impetus for quality improvement efforts to improve upon secondary prevention measures and reduce the morbidity and mortality of patients with known IHD

A Risk Score for Predicting Multiple Sclerosis

Multiple sclerosis (MS) develops as a result of environmental influences on the genetically susceptible. Siblings of people with MS have an increased risk of both MS and demonstrating asymptomatic changes in keeping with MS. We set out to develop an MS risk score integrating both genetic and environmental risk factors. We used this score to identify siblings at extremes of MS risk and attempted to validate the score using brain MRI.78 probands with MS, 121 of their unaffected siblings and 103 healthy controls were studied. Personal history was taken, and serological and genetic analysis using the illumina immunochip was performed. Odds ratios for MS associated with each risk factor were derived from existing literature, and the log values of the odds ratios from each of the risk factors were combined in an additive model to provide an overall score. Scores were initially calculated using log odds ratio from the HLA-DRB1*1501 allele only, secondly using data from all MS-associated SNPs identified in the 2011 GWAS. Subjects with extreme risk scores underwent validation studies. MRI was performed on selected individuals.There was a significant difference in the both risk scores between people with MS, their unaffected siblings and healthy controls (p<0.0005). Unaffected siblings had a risk score intermediate to people with MS and controls (p<0.0005). The best performing risk score generated an AUC of 0.82 (95%CI 0.75–0.88).The risk score demonstrates an AUC on the threshold for clinical utility. Our score enables the identification of a high-risk sibling group to inform pre-symptomatic longitudinal studies