Mortality in rheumatoid disease

This paper provides an overview of rheumatoid disease from the perspective of its impact on mortality. The term, rheumatoid arthritis, may promote the misconception that this disease is relatively trivial and easily managed; therefore, "rheumatoid disease" is preferred. Numerous long-term studies in many settings have established that significant excess mortality is associated with rheumatoid disease, and that this excess mortality is related to cardiovascular disease deaths. Inflammation in rheumatoid and cardiovascular diseases shares the same biologic mechanisms. Severity of extraarticular disease, decline in functional level, and level of inflammatory activity are associated with increased risk of mortality. Detection and measurement of novel inflammatory biomarkers may provide tools to assess prognosis and to monitor therapy. Close attention to the management of traditional cardiovascular risk factors is essential in these patients. Whether disease modifying antirheumatic drug (DMARD) therapy will reduce all-cause and cardiovascular disease mortality in rheumatoid disease is the subject of ongoing studies.     

Screening potential elderly preferred markers: exploratory analysis of Cardiovascular Health Study (CHS) data

The Cardiovascular Health Study (CHS) analyzes risk factors for coronary heart disease and stroke in people age 65 and older. Since CHS is designed to comprehensively study cardiovascular risk factors in an elderly population, it provides a unique opportunity to study the association of risk factors with mortality, as well as morbidity risk. With the growth of the elderly as population and life insurance market segments, the need to more precisely stratify mortality within a standard risk group of the elderly has grown as well. This exploratory analysis assesses medical factors that could be used to improve mortality risk stratification within a "standard" mortality population, using the CHS public use data set. Participants with a personal history of cardiovascular disease, diabetes, or major electrocardiographic abnormalities were excluded from the analysis in order to mimic a standard life insurance selection process. Then, Cox proportional hazards regression was used to study 10 medical risk factors. This model suggested that forced vital capacity >80% predicted, serum creatinine <1.5 mg/dL (133 mcmol/L), hemoglobin >11 g/dL (110 g/L), and serum albumin >3.5 mg/L (35 mmol/ L) are significantly associated (p = 0.05) with favorable mortality. C-reactive protein <1 mg/L is associated with favorable mortality at borderline significance levels (p = 0.09). On the other hand, a family history of cardiovascular disease (MI and/or stroke) and low BMI (<26 kg/m2) are associated with unfavorable mortality in the analysis. Total to HDL cholesterol ratio of <6, presence of supine systolic blood pressure < or = 140 mmHg, and the presence of minor rest electrocardiographic findings were not statistically significant factors in the multivariate model. Further assessment of the predictive value of the "significant" medical factors identified is required in insured lives.     

Ankle/arm blood pressure index: an insurance perspective

Recent studies conclude that the ankle/arm blood pressure index (AAI) is a useful clinical tool for refining cardiovascular risk classification in the elderly. A reduction in the AAI to 0.9 or less is associated with increased risk for both coronary heart disease and total cardiovascular disease morbidity and mortality, as well as all-cause mortality. This relationship persists after adjusting for traditional risk factors and known cardiovascular disease. AAI will appear more common in attending physician's statements, prompting a need to educate underwriters about this technology. AAI may be of particular interest to insurers dealing in the elderly market, to those with strong physician examiner systems, and in markets where blood or urine tests are not commonly used in underwriting.     

Comparison of the mortality between ischemia and frequent premature ventricular contractions on an exercise test

Ischemia on an exercise test (ET) is a known risk factor for cardiovascular mortality. However, the magnitude of risk of frequent premature ventricular contractions (PVCs) on ET is often overlooked. This analysis reveals that the quantitative additional mortality risk on ET presented by frequent PVCs is similar to ischemia.     

Metabolic syndrome

This paper reviews current diagnostic criteria for Metabolic Syndrome, and provides in-depth discussion of the component abnormalities. A cluster of abnormalities defines Metabolic Syndrome including insulin resistance, hypertension, obesity, hypertriglyceridemia, and low HDL cholesterol. Evidence that inflammation is another component of Metabolic Syndrome raises the possibility that this is an additional process that links Metabolic Syndrome to cardiovascular disease (CVD) risk. Population studies strongly suggest the existence of a relationship between the metabolic abnormalities associated with Metabolic Syndrome and the development of diabetes and cardiovascular disease. It appears that lifestyle modifications can contribute to the prevention of progression to diabetes and the reduction of individual CVD risk factors. Whether use of insulin sensitizing drugs can significantly delay or prevent the progression to diabetes is under investigation. Because of its contribution to the growing prevalence of type 2 diabetes, and the associated increased CVD risk, the recognition of Metabolic Syndrome and its consequences are critical in the course of morbidity and mortality risk assessment.     

Diabetes mellitus--long time survival

The medical literature of the last decade enables us to estimate survival of diabetics. Insulin dependent diabetic (IDDM) present a 3 to 6-fold mortality and die after age 30, the most frequent causes being end stage renal and vascular diseases. Non insulin-dependent diabetic (NIDDM) mortality is 1.4 to 3.7 times that of non-diabetics. Cardiovascular events and strokes are the major causes of death. Pancreatic carcinoma occurs twice as frequently in NIDDM compared to non-diabetics. Early markers of late severe complications are hypertension and proteinuria. Retinopathy has little influence on morality if other risk factors are considered. Yet, glaucoma and lens changes are associated with three- and twofold mortalities. One of five IDDM with microalbuminuria progresses to overt nephropathy in 5 years. In NIDDM micro-albuminuria predicts cardiovascular disease with a mortality of up to 2 times. Careful treatment of cardiovascular risk factors and of microalbuminuria combined with optimal metabolic control substantially reduces mortality of diabetics.     

C-reactive protein--a screening test for coronary disease?

C-reactive protein (CRP) is one of a number of substances termed "acute phase reactants," biologic substances that appear in the circulation when an active inflammatory process occurs. Although traditionally used to monitor or detect major infectious or inflammatory conditions, elevations of CRP levels within the conventional range of "normals" has been intensively studied as a marker for coronary disease and risk of future coronary events. Sensitive assays that can be performed on a high-volume, commercial basis are now available. CRP appears to be a valuable marker for the prediction of future events in individuals who have known coronary artery disease. CRP has been proposed as a coronary disease-screening test for healthy individuals; however, available data suggest that use of CRP in this context may be premature. This paper reviews published research concerning CRP and the prediction of cardiovascular and total mortality risk, then outlines the current "state of the art" for the application of CRP to the risk assessment process.     

Older age underwriting: frisky vs frail

The speed of the aging process is variable. Some individuals remain exceptionally fit beyond age 90, while others become frail and fragile early. Survival is better predicted by biological age (state of health, status of reserves) rather than chronological age (age in years since date of birth). The frail group shows a higher mortality compared to the robust group. When assessing the elderly in underwriting, it is important to note the usual chronic diseases such as cardiovascular disease, COPD, cancer risk, and so on. But because of its strong impact on prognosis, it is also important to assess frailty. Key features of frailty are social isolation, dependency in managing life activities and self-care, cognitive decline, shrinking of bone and muscle mass, and slow weight loss.     

Modeling total cholesterol as predictor of mortality: the low-cholesterol paradox

Elevated total cholesterol is well-established as a risk factor for coronary artery disease and cardiovascular mortality. However, less attention is paid to the association between low cholesterol levels and mortality--the low cholesterol paradox. In this paper, restricted cubic splines (RCS) and complex survey methodology are used to show the low-cholesterol paradox is present in the laboratory, examination, and mortality follow-up data from the Third National Health and Nutrition Examination Survey (NHANES III). A series of Cox proportional hazard models, demonstrate that RCS are necessary to incorporate desired covariates while avoiding the use of categorical variables. Valid concerns regarding the accuracy of such predictive models are discussed. The one certain conclusion is that low cholesterol levels are markers for excess mortality, just as are high levels. Restricted cubic splines provide the necessary flexibility to demonstrate the U-shaped relationship between cholesterol and mortality without resorting to binning results. Cox PH models perform well at identifying associations between risk factors and outcomes of interest such as mortality. However, the predictions from such a model may not be as accurate as common statistics suggest and predictive models should be used with caution.     

On systematic mortality risk and risk-minimization with survivor swaps

A new market for so-called mortality derivatives is now appearing with survivor swaps (also called mortality swaps), longevity bonds and other specialized solutions. The development of these new financial instruments is triggered by the increased focus on the systematic mortality risk inherent in life insurance contracts, and their main focus is thus to allow the life insurance companies to hedge their systematic mortality risk. At the same time, this new class of financial contract is interesting from an investor's point of view, since it increases the possibility for an investor to diversify the investment portfolio. The systematic mortality risk stems from the uncertainty related to the future development of the mortality intensities. Mathematically, this uncertainty is described by modeling the underlying mortality intensities via stochastic processes. We consider two different portfolios of insured lives, where the underlying mortality intensities are correlated, and study the combined financial and mortality risk inherent in a portfolio of general life insurance contracts. In order to hedge this risk, we allow for investments in survivor swaps and derive risk-minimizing strategies in markets where such contracts are available. The strategies are evaluated numerically.     

Stroke--incidence, mortality, morbidity and risk

In the United States, 700,000 strokes, responsible for 165,000 deaths, occur each year. Worldwide, stroke is the 2nd leading cause of death. Stroke is a major health problem; and as the population ages, its significance will grow. This paper reviews the epidemiology of stroke, the identification of modifiable risk factors, and some of the options for intervention that can reduce stroke-related mortality and morbidity. Though the diagnosis and care of stroke patients has improved, mortality resultant from stroke remains significant, with only 50% 5-year survival in some clinical studies. The risk of stroke following a transient ischemic attack (TIA) or initial stroke is also significant-approximately 30% following either event. Stroke severity at onset and patient age are the most important factors for predicting prognosis. Stroke prevention focuses on management of the traditional cardiovascular risk factors especially control of blood pressure and smoking cessation. The role of diabetes and lipid control in stroke prevention continues to be studied. The optimum use of anticoagulation to reduce stroke risk has been explored by the Stroke in Patients with Atrial Fibrillation (SPAF) studies. Carotid endarterectomy is effective in stroke prevention for those with symptomatic carotid obstruction of 70%, but its role in other scenarios is less certain. Antiplatelet drugs continue to be an important therapy for the prevention of recurrent stroke. Centralized stroke centers that specialize in stroke diagnosis and care along with rapidly rendering appropriate treatment can improve mortality and morbidity of stroke by 20%.     

The Metabolic Syndrome and All-Cause Mortality in an Insured Lives Population

Abstract

Metabolic syndrome and its association with mortality have not been studied in insured lives populations. The Swiss Re Study evaluated metabolic syndrome prevalence and associated mortality from all causes and circulatory disease in a cohort of 35,470 predominantly healthy individuals, aged 18–83 years, who were issued life insurance policies between 1986 and 1997. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III guidelines. The NCEP obesity criteria were modified with a prediction equation using body mass index, gender, and age substituted for waist circumference. Adjustments also were made for nonfasting triglyceride and blood glucose values. Risk ratios for policyholders identified with metabolic syndrome were 1.16 (P = .156) for mortality from all causes and 1.45 (P = .080) for mortality from circulatory disease compared with individuals without the syndrome. Risk was proportional to the number of components, or score, of the metabolic syndrome present. Risk ratios for metabolic syndrome score were 1.14 (P < .001) for mortality from all causes and 1.38 (P < .001) for mortality from circulatory disease compared with individuals without metabolic syndrome factors. In both all-cause and circulatory death models, relative risk was highest for the blood pressure risk factor. Based on a modified NCEP definition, increased mortality risk is associated with metabolic syndrome in an insured lives cohort and has life insurance mortality pricing implications.     

两因子随机死亡率状态空间模型及长寿风险测度

引入状态空间模型对传统两因子CBD模型拟合阶段和预测阶段进行联合建模,并基于卡尔曼滤波方法对模型参数进行估计。进一步考虑到死亡率数据的小样本特征,结合Bootstrap仿真技术和生存年金组合折现模型对长寿风险进行测度。利用1996~2011年数据展开实证研究,结果表明:结合模型解释能力、参数估计结果和误差项正态分布检验结果,两因子状态空间模型要优于传统CBD模型;年金组合规模的扩大可以消除微观长寿风险,但不能消除宏观长寿风险和参数风险;宏观长寿风险占据着不可分散风险的主导地位。     

Risk Classification by Fuzzy Inference

Traditionally, policyholders in life insurance are classified in simple mortality tables, most often according to only a few risk characteristics. Instead of a risk classification according to the numerical rating system, this article describes how to classify by using a fuzzy inference methodology. By defining risk factors as fuzzy sets, it is shown that an insurer can utilize multiple prognostic factors that are imprecise and vague. The presented fuzzy risk classification provides a more realistic way of modeling mortality risks since it allows for compensations and interactions between multiple risk factors.     

Update on coronary artery calcium imaging

This update of coronary calcium imaging discusses methods of detecting and measuring coronary artery calcium and their correlation to coronary artery disease risk. The value of EBCT to traditional non-invasive cardiovascular tests is compared. A negative EBCT test makes the presence of atherosclerotic plaque, including unstable plaque, very unlikely. Negative EBCT may be consistent with low risk of a cardiovascular event over the next 2-5 years. Conversely, positive EBCT confirms the presence of a coronary plaque. The greater the amount of calcium, the greater the likelihood of occlusive disease, but there is a not a 1:1 relationship and findings may not be site specific. A high calcium score may be consistent with moderate to high risk of cardiovascular event within the next 2-5 years. Limitations and cautions concerning the general use of EBCT for screening are discussed.     

Matters of the athletic heart

Frequently an underwriter or medical director will question whether an increase in left ventricular mass represents pathologic left ventricular hypertrophy (LVH) or physiologic changes related to exercise. The LVH condition reflects end-organ damage related to abnormal hemodynamic stresses and confers an increased morbidity and mortality risk. When left ventricular mass is increased because of exercise, measured changes represent a normal, healthy cardiovascular system responding to the demands of that exercise. This article summarizes medical findings that distinguish pathologic LVH from an "athletic heart."     

Modeling and Pricing Longevity Derivatives Using Stochastic Mortality Rates and the Esscher Transform

The Lee-Carter mortality model provides a structure for stochastically modeling mortality rates incorporating both time (year) and age mortality dynamics. Their model is constructed by modeling the mortality rate as a function of both an age and a year effect. Recently the MBMM model (Mitchell et al. 2013) showed the Lee Carter model can be improved by fitting with the growth rates of mortality rates over time and age rather than the mortality rates themselves. The MBMM modification of the Lee-Carter model performs better than the original and many of the subsequent variants. In order to model the mortality rate under the martingale measure and to apply it for pricing the longevity derivatives, we adapt the MBMM structure and introduce a Lévy stochastic process with a normal inverse Gaussian (NIG) distribution in our model. The model has two advantages in addition to better fit: first, it can mimic the jumps in the mortality rates since the NIG distribution is fat-tailed with high kurtosis, and, second, this mortality model lends itself to pricing of longevity derivatives based on the assumed mortality model. Using the Esscher transformation we show how to find a related martingale measure, allowing martingale pricing for mortality/longevity risk–related derivatives. Finally, we apply our model to pricing a q-forward longevity derivative utilizing the structure proposed by Life and Longevity Markets Association.     

A Two-Factor Model for Stochastic Mortality with Parameter Uncertainty: Theory and Calibration

In this article, we consider the evolution of the post‐age‐60 mortality curve in the United Kingdom and its impact on the pricing of the risk associated with aggregate mortality improvements over time: so‐called longevity risk. We introduce a two‐factor stochastic model for the development of this curve through time. The first factor affects mortality‐rate dynamics at all ages in the same way, whereas the second factor affects mortality‐rate dynamics at higher ages much more than at lower ages. The article then examines the pricing of longevity bonds with different terms to maturity referenced to different cohorts. We find that longevity risk over relatively short time horizons is very low, but at horizons in excess of ten years it begins to pick up very rapidly. A key component of the article is the proposal and development of a method for calculating the market risk‐adjusted price of a longevity bond. The proposed adjustment includes not just an allowance for the underlying stochastic mortality, but also makes an allowance for parameter risk. We utilize the pricing information contained in the November 2004 European Investment Bank longevity bond to make inferences about the likely market prices of the risks in the model. Based on these, we investigate how future issues might be priced to ensure an absence of arbitrage between bonds with different characteristics.     

Proteinuria as a mortality risk

This case report examines the factors involved in the mortality risk of low-grade proteinuria. Proteinuria and microalbuminuria are defined and the use of the protein-creatinine ratio is discussed. Studies from the medical literature suggest that albuminuria complements risk selection in diabetics and nondiabetics and may parallel or adversely modify other cardiovascular risk factors.     

Gene-environment interactions and the complexity of human genetic diseases

In the assessment of mortality and morbidity risk, the ability of family history and genetic test results to predict the age of occurrence, severity, and long-term prognosis of 'genetic' diseases is important. An increasing number of gene-gene and gene-environment interactions have been demonstrated in a number of monogenic Mendelian diseases. These interactions can significantly modify the clinical presentation (disease phenotype) of diseases previously regarded purely as 'genetic.' As a result, 'genetic' diseases can be positioned in a continuum between classic Mendelian and complex disease where the extremes, pure genetic or solely non-genetic, do not exist. The position of any given disease in this continuum is defined by three components: the major gene(s) contributing to the phenotype, the variability added by modifier genes and the significance of environmental factors influencing the phenotype. As the predictive value of genetic test results can be significantly influenced by additional genetic and environmental risk factors, a better understanding of these factors may influence the quantification of mortality and morbidity risk.