Residual Lifetime Risk Research Articles

Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy.

Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient's age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.

Potential lifetime benefit of applying two-step ESC prevention strategy

Abstract Background The 2021 ESC Prevention guideline recommends a two-step strategy for risk management in patients with atherosclerotic cardiovascular disease (ASCVD). We estimated the potential lifetime benefit of complete implementation of this approach, compared to current practice. Methods In a pooled cohort (N=1,937) of coronary patients >45 years, lifetime risk for recurrent events and gained event-free years with STEP 1 and STEP 2 were estimated using the SMART-REACH model. For all patients, STEP 1 included non-smoking, the use of antiplatelet therapy and specific targets for low-density lipoprotein cholesterol (LDL-C<1.8 mmol/L) and systolic blood pressure (SBP<140 mmHg), with use of diabetic medication if indicated. In patients with residual lifetime risk >30%, STEP 2 included stricter targets (LDL-C<1.4 mmol/L and SBP<130 mmHg) and intensified treatments (colchicine and dual antiplatelet therapy). Results With current treatment following a coronary event, 196 (10%) of patients (20% women, mean age 64) met targets of STEP 1 and 46 (2%) of STEP 2, indicating a lifetime risk of 52% [interquartile range (IQR) 45-59]. Implementing STEP 1 would lower lifetime risk to 37% [IQR 28-45] (Fig 1) and result in a gain of 3.2 [IQR 1.4-5.9] years without events (Fig 2). Intensified STEP 2 treatment was indicated in 70% (median residual risk 41% [36-48]), resulting in lifetime risk in all patients of 26% [21-31] and 5.5 [3.8-8.1] event-free years. Conclusion A two-step (residual) risk reduction strategy in ASCVD patients has the potential to lower lifetime risk of recurrent events and to approximately add three event-free years per step to their lifetime.Decrease in lifetime risk per stepGain of event-free years per step

Lifetime risk of developing peripheral arterial disease: a nationwide longitudinal study

Abstract Background Peripheral arterial disease (PAD) presents a substantial clinical and public health burden. It remains one of the most impactful cardiovascular conditions in terms of both number of affected individuals and its impact on the individual’s survival, functional ability, and quality of life. Nonetheless, comprehensive data on the risk of developing PAD in the general population is scant. Purpose We aimed to quantify the lifetime risk of physician-diagnosed PAD in an unselected, nationwide population. Methods We conducted analyses of the entire Danish population aged 40 years and older from 2000 through 2018 using nationwide health administrative data. All individuals free of PAD were followed for up to 19 years. The cumulative incidence and residual lifetime risk of PAD adjusted for the competing risk of death was estimated by a modified survival analysis technique. Results were stratified by age, sex, and socioeconomic status. Results The Danish population aged 40-99 years in 2000-2018 included 4,508,932 individuals, among whom 123,479 individuals were diagnosed with PAD during follow-up. The overall lifetime risk from age 40 years during the remaining lifetime was 19.9% (95% CI 19.8%-20.2%). Lifetime risk was higher in men than in women (22.7% vs. 17.8%) and among individuals living alone (22.4% among unmarried or divorced individuals vs. 19.4% among married individuals). The highest lifetime risks were observed among individuals of lower socioeconomic status, especially individuals receiving social welfare payments for whom the lifetime risk exceeded 26%. The residual risk of developing PAD fell with age; for example, a 50-year-old who had not been diagnosed with PAD would still have a 19.6% residual risk during the remaining lifetime, whereas it was 15.4% among individuals aged 70 years. Conclusions About one in five individuals are likely to be diagnosed and receive medical attention for PAD during their lifetime with substantial disparities among individual of lower socioeconomic status. This knowledge may be used in public health awareness campaigns and to promote effective strategies to prevent PAD and limit progression in those with the disease and ensure the highest life quality possible.

Genetic Prediction of Lifetime Risk of Fracture.

Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.

A comparison of statistical methods to predict the residual lifetime risk.

Lifetime risk measures the cumulative risk for developing a disease over one's lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.

Lifetime Risk of Heart Failure Among Participants in the Framingham Study

BackgroundThe residual lifetime risk (RLR) of developing heart failure (HF) may have changed over time because of the increasing population burden of hypertension, obesity, and diabetes; greater survival after myocardial infarction; and a greater lifespan. ObjectivesThe authors assessed changes in the RLR for HF in two 25-year epochs (1965-1989 and 1990-2014). MethodsWe compared the RLR of HF at age 50 years (adjusting for competing risk of death) in the 2 epochs in Framingham Study participants overall and in the following strata: sex, body mass index, blood pressure, and diabetes. ResultsMean life expectancy increased from 75.9 to 82.1 years in women and 72.5 to 78.1 years in men. We observed 624 HF events over 111,351 person-observations in epoch 1, and 875 HF events over 128,903 person-observations in epoch 2. The mean age at onset of HF increased across the epochs by 6.6 years (women) to 7.2 years (men). The RLR of HF at age 50 years increased across epochs from 18.86% to 22.55% (absolute increase 3.69; 95% CI: 0.90-6.49; P = 0.01) in women, and from 19.19% to 25.25% (absolute increase 6.06; 95% CI: 3.08-9.04; P < 0.001) in men. The increase in RLR of HF in the second epoch was consistent across strata with excess body mass index or higher blood pressure (relative increase of 28%-47%) and in participants without prior myocardial infarction (relative increase of 23%). ConclusionsThe RLR of HF has increased in our community-based sample of White individuals over the last 5 decades, possibly caused by an increase in life expectancy.

Lifetime Risk of Heart Failure and Trends in Incidence Rates Among Individuals With Type 2 Diabetes Between 1995 and 2018.

BackgroundThere are limited data on the lifetime risk of heart failure (HF) in people with type 2 diabetes and how incidence has changed over time. We estimated the cumulative incidence and incidence rates of HF among Danish adults with type 2 diabetes between 1995 and 2018 using nationwide data.Methods and ResultsIn total, 398 422 patients (49% women) with type 2 diabetes were identified. During follow‐up, 36 400 (9%) were diagnosed with HF and 121 459 (30%) were censored due to death. Using the Aalen‐Johansen estimators, accounting for the risk of death, the estimated residual lifetime risk of HF at age 50 years was calculated as 24% (95% CI 22%–27%) in women and 27% (25%–28%) in men. During the observational period, the proportion of patients treated with statins, angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers, and metformin increased from <30% to >60%. Similarly, the annual incidence rates of HF decreased significantly, with declines being greater in older versus younger individuals (5% versus 2% in age >50 versus ≤50 years, respectively; P<0.0001) and in women versus men (5% versus 4%, P=0.02), but similar in patients with and without IHD (4% versus 4%, P=0.53).ConclusionsThe current lifetime risk of HF in type 2 diabetes approximates 1 in 4 for men and women. Paralleled by an increase in use of evidence‐based pharmacotherapy over the past decades, the risk of developing HF has declined across several subgroups and regardless of underlying IHD, suggesting that optimal diabetes treatment can mitigate HF risk.

Modifiable lifetime risk for recurrent major cardiovascular events: observations in a contemporary pooled cohort

Abstract Introduction The major modifiable risk factors for atherosclerosis – lifestyle, hypertension, diabetes and cholesterol – collectively account for 80 to 90% of disease burden. Currently, the majority of coronary patients does not meet the guideline-directed treatment targets for these risk factors, resulting in high levels of residual risk. An increasing number of novel preventive drugs aims to reduce this residual risk, but are not considered cost-effective when added routinely to all patients. Quantifying the potential lifetime risk reduction one year after an acute coronary syndrome (ACS) may aid in optimum use of available treatment and value-based use of novel drugs. Purpose The purpose of this analysis was to quantify the loss of lifetime risk reduction due to suboptimal modifiable risk factor control in patients with prior ACS or revascularisation. Methods We pooled six recent prospective studies (Response 1 [1] and 2 [2], Opticare [3], EuroAspire IV [4] and V [5] and HELIUS [6]) with Dutch patients (n=3,230, 24% women) at mean age 61±8 years and follow-up at median 1.1 [IQR 1.0–1.8] years after an ACS or revascularisation. We investigated individual lifestyle- and drug-modifiable risk factors at guideline-directed targets. Using the SMART-REACH model [7], we calculated % reduction of individual residual lifetime risk for myocardial infarction, stroke, or cardiovascular death and event free years gained by the change from current treatment to a (simulated) guideline-directed optimal situation. Results Risk factor control was far from optimal: only 7% met all lifestyle-related risk targets, whereas 10% met none: 30% persist smoking, 79% was overweight (BMI ≥25 kg/m2), of which 40% obese (BMI ≥30 kg/m2), and 45% reported insufficient physical activity (&amp;lt;150 minutes per week). Systolic blood pressure ≥140 mmHg was found in 40%, and LDL-cholesterol ≥1.8 mmol/L or ≥2.5 mmol/L (depending on the target at that time) in 65%. Basic preventive medication use was, however, common: 87% used antithrombotic agents, 85% lipid lowering drugs and 86% any blood pressure lowering drugs. By the change from current to optimal guideline-directed treatment, residual lifetime risk for cardiovascular events and cardiovascular death would decrease from a mean of 54±11% to 25±10% (Figure 1), and a median of 7.4 [IQR 5.2–10.6] event free years would be gained (Figure 2). Conclusion Suboptimal risk factor control resulted in avoidable high residual lifetime risk of myocardial infarction, stroke, or cardiovascular death and loss of event free years in patients with prior ACS or revascularisation. This finding highlights the unexploited potential of optimised use of available lifestyle- and drug treatment to significantly reduce residual lifetime risk. Funding Acknowledgement Type of funding sources: None. Figure 1. Modifiable residual lifetime riskFigure 2. Lifetime benefit in CVD event free years

Lifetime Risk of Lower-Extremity Peripheral Artery Disease Defined by Ankle-Brachial Index in the United States.

BackgroundThere are no available lifetime risk estimates of lower‐extremity peripheral artery disease (PAD).Methods and ResultsUsing data from 6 US community‐based cohorts and the vital statistics, we estimated the prevalence and incidence of PAD, defined as an ankle‐brachial index < 0.90, at each year of age from birth to 80 years for white, black, and Hispanic men and women. Then, we used Markov Monte Carlo simulations in a simulated cohort of 100 000 individuals to estimate lifetime risk of PAD. On the basis of odds ratios of PAD for traditional atherosclerotic risk factors (eg, diabetes mellitus and smoking), we developed a calculator providing residual lifetime risk of PAD. In an 80‐year horizon, lifetime risks of PAD were 30.0% in black men and 27.6% in black women, but ≈19% in white men and women and ≈22% in Hispanic men and women. From another perspective, 9% of blacks were estimated to develop PAD by 60 years of age, while the same proportion was seen at ≈70 years for whites and Hispanics. The residual lifetime risk within the same race/ethnicity varied by 3.5‐ to 5‐fold according to risk factors (eg, residual lifetime risk in 45‐year‐old black men was 19.9% when current smoking, diabetes mellitus, and history of cardiovascular disease were absent versus 70.4% when all were present).ConclusionsIn the United States, ≈30% of blacks are estimated to develop PAD during their lifetime, whereas the corresponding estimate is ≈20% for whites and Hispanics. The residual lifetime risk within the same race/ethnicity substantially varies according to traditional risk factors.

Estimation of the individual residual risk of cervical cancer after vaccination with the nonavalent HPV vaccine

ABSTRACTBackground: The nonavalent HPV (9vHPV) vaccine is indicated for active immunisation of individuals from the age of 9 years against cervical, vulvar, vaginal and anal premalignant lesions and cancers causally related to vaccine HPV high risk types 16, 18, 31, 33, 45, 52 and 58, and to the HPV low risk types 6 and 11, causing genital warts.Objective: To estimate the lifetime risk (up to the age of 75 years) for developing cervical cancer after vaccinating a HPV naïve girl (e.g. 9 to 12 years old) with the 9vHPV vaccine in the hypothetical absence of cervical cancer screening.Methods: We built Monte Carlo simulation models using historical pre-screening age-specific cancer incidence data and current mortality data from Denmark, Finland, Norway, Sweden and the UK. Estimates of genotype contribution fractions and vaccine efficacy were used to estimate the residual lifetime risk after vaccination assuming lifelong protection.Results: We estimated that, in the hypothetical absence of cervical screening and assuming lifelong protection, 9vHPV vaccination reduced the lifetime cervical cancer and mortality risks 7-fold with a residual lifetime cancer risks ranging from 1/572 (UK) to 1/238 (Denmark) and mortality risks ranging from 1/1488 (UK) to 1/851 (Denmark). After decades of repetitive cervical screenings, the lifetime cervical cancer and mortality risks was reduced between 2- and 4-fold depending on the country.Conclusion: Our simulations demonstrate how evidence can be generated to support decision-making by individual healthcare seekers regarding cervical cancer prevention.

SSA 01-4 THE CHARACTERISTICS OF ARTERIAL STIFFNESS IN EAST ASIA

Aging causes progressive changes in the structure and function of the large arteries that adversely impact the heart and vital organs. Vascular aging is a major independent risk factor for the development of cardiovascular diseases and events. Arterial stiffening is the dominant hemodynamic manifestation of vascular aging and a major independent predictor for incident hypertension. Arterial stiffening is therefore responsible for the very high residual lifetime risk for hypertension for middle-aged and elderly individuals. Asian populations may have a predisposition to increased central aortic pulse pressure because of the relatively larger diameter and thinner media at the proximal aorta that affect the interaction between ventricular ejection and arterial load. Increased arterial stiffness with aging was confirmed in several Asian populations, using either carotid-femoral pulse wave velocity (cf-PWV) or brachial-ankle pulse wave velocity (ba-PWV). Both cf-PWV and ba-PWV have been recognized as an independent predictor for cardiovascular events and all-cause mortality in Asian populations. In Asian populations, vascular aging-related medial degeneration but not atherosclerosis is the dominant factor associated with increased arterial stiffness with age. Salt intake has an independent effect on arterial wall properties contributing to increased arterial stiffness with age. Systolic hypertension is a consequence and an accelerator of the vascular aging related arterial stiffness. Asian subjects with systolic hypertension may be more prone to risks of cardiovascular disease, mortality and renal function decline than Western subjects. Strategies to prevent arterial stiffness and control systolic hypertension are urgently needed for the rapidly aging Asian populations.

Residual lifetime risk of chronic kidney disease.

An accurate estimation of the lifetime risk of chronic kidney disease (CKD) can aid in patient education while also informing the development of public health screening programs and educational campaigns. Framingham Offspring Study participants were included if they were free of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at age 50 years and had at least two serum creatinine measures during follow-up (mean 16 years, 49 506 person-years). We estimated the lifetime risk of CKD to age 90 years adjusting for the competing risk of death in the overall cohort and in population subgroups with known CKD risk factors including hypertension, obesity and diabetes. Overall 3362 individuals (52% women) were included in the study. Mean age at study baseline was 54 years. By the end of the study, 729 individuals (21.7%) developed CKD and 618 (18.4%) died. At age 50 years, the cumulative lifetime risk of CKD was 41.3% [95% confidence interval (CI) 38.5-44.0]. The risk was increased in those with risk factors at baseline including diabetes (52.6%, 95% CI 44.8-60.4), hypertension (50.2%, 95% CI 46.1-54.3) and obesity (46.5%, 95% CI 41.1-52.0). For those individuals without any risk factors at baseline, the lifetime risk of CKD was lower (34.2%, 95% CI 29.4-39.0) relative to those with 1, 2 or 3 risk factors (45.0, 51.5 and 56.1% respectively, P < 0.01 for all compared with those with no risk factors). Four out of 10 individuals without CKD at age 50 years will eventually develop CKD. This risk is modified by the presence of hypertension, diabetes and obesity at baseline. This demonstrates the importance of early identification of CKD risk factors, to aid in patient education, and potentially to reduce the future risk of disease.

Impact of hypertension on the lifetime risk of coronary heart disease.

The lifetime risk estimate conveys the probability of disease in the remaining lifetime for an index age. These estimates may be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on the impact of hypertension on the lifetime risk of cardiovascular events. The Suita Study, a cohort study of urban residents, was established in 1989. We included all participants who were coronary heart disease (CHD) free at baseline. Age (in years) was used as the timescale. Age-specific incidence rates were calculated with the person-year method within 5-year bands. We estimated the sex- and index-age-specific lifetime risk of first-ever CHD, taking the competing risk of death into account. We followed 5834 participants from 1989 to 2007 for a total of 75 387.5 person-years. At age 45 years, the competing risk of death-adjusted lifetime risk for all CHD for men was 14.12% for normotensive men and 26.95% for hypertensive men. The competing risk of death-adjusted lifetime risk for all CHD at 45 years of age for women was 6.21% for normotensive women and 14.85% for hypertensive women. This increased lifetime risk of CHD for hypertensive patients was observed among both men and women across all index ages. Although the overall lifetime risk of CHD was lower than in the Western population, hypertension showed a significant effect on the residual lifetime risk of CHD among Japanese middle-aged men and women. This easy-to-understand knowledge may be used as an important index to assist public health education and planning.

IPrevent®: a tailored, web-based, decision support tool for breast cancer risk assessment and management.

We aimed to develop a user-centered, web-based, decision support tool for breast cancer risk assessment and personalized risk management. Using a novel model choice algorithm, iPrevent® selects one of two validated breast cancer risk estimation models (IBIS or BOADICEA), based on risk factor data entered by the user. Resulting risk estimates are presented in simple language and graphic formats for easy comprehension. iPrevent® then presents risk-adapted, evidence-based, guideline-endorsed management options. Development was an iterative process with regular feedback from multidisciplinary experts and consumers. To verify iPrevent®, risk factor data for 127 cases derived from the Australian Breast Cancer Family Study were entered into iPrevent®, IBIS (v7.02), and BOADICEA (v3.0). Consistency of the model chosen by iPrevent® (i.e., IBIS or BOADICEA) with the programmed iPrevent® model choice algorithm was assessed. Estimated breast cancer risks from iPrevent® were compared with those attained directly from the chosen risk assessment model (IBIS or BOADICEA). Risk management interventions displayed by iPrevent® were assessed for appropriateness. Risk estimation model choice was 100 % consistent with the programmed iPrevent® logic. Discrepant 10-year and residual lifetime risk estimates of >1 % were found for 1 and 4 cases, respectively, none was clinically significant (maximal variation 1.4 %). Risk management interventions suggested by iPrevent® were 100 % appropriate. iPrevent® successfully integrates the IBIS and BOADICEA risk assessment models into a decision support tool that provides evidence-based, risk-adapted risk management advice. This may help to facilitate precision breast cancer prevention discussions between women and their healthcare providers.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3726-y) contains supplementary material, which is available to authorized users.

Expected lifetime numbers, risks, and burden of osteoporotic fractures for 50-year old Chinese women: a discrete event simulation incorporating FRAX.

This work was undertaken to provide an estimation of expected lifetime numbers, risks, and burden of fractures for 50-year-old Chinese women. A discrete event simulation model was developed to simulate the lifetime fractures of 50-year-old Chinese women at average risk of osteoporotic fracture. Main events in the model included hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture. Fracture risks were calculated using the FRAX® tool. Simulations of 50-year-old Chinese women without fracture risks were also carried out as a comparison to determine the burden of fractures. A 50-year-old Chinese woman at average risk of fracture is expected to experience 0.135 (95% CI: 0.134-0.137) hip fractures, 0.120 (95% CI: 0.119-0.122) clinical vertebral fractures, 0.095 (95% CI: 0.094-0.096) wrist fractures, 0.079 (95% CI: 0.078-0.080) humerus fractures, and 0.407 (95% CI: 0.404-0.410) other fractures over the remainder of her life. The residual lifetime risk of any fracture, hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture for a 50-year-old Chinese woman is 37.36, 11.77, 10.47, 8.61, 7.30, and 27.80%, respectively. The fracture-attributable excess quality-adjusted life year (QALY) loss and lifetime costs are estimated at 0.11 QALYs (95% CI: 0.00-0.22 QALYs) and US $714.61 (95% CI: US $709.20-720.02), totaling a net monetary benefit loss of US $1,104.43 (95% CI: US $904.09-1,304.78). Chinese women 50years of age are at high risk of osteoporotic fracture, and the expected economic and quality-of-life burden attributable to osteoporotic fractures among Chinese women is substantial.

Vitamin D und postmenopausale Knochengesundheit

Fractures contribute significantly to morbidity and mortality of postmenopausal women. Among postmenopausal women aged 60 years and older, the mortality-adjusted residual lifetime risk of fracture has been estimated to be 44–65 %. Thus, effective strategies are urgently needed to prevent fractures among postmenopausal women. This review summarizes the available evidence that supports vitamin D3 supplementation at a dose of 800 IU per day as a strategy to reduce falls and fractures, including hip fractures, among postmenopausal women by about 20–30 %. This recommendation is supported by the Position Statement on Vitamin D of the International Osteoporosis Foundation, the 2011 World Osteoporosis Day Report, and the US Endocrine Society. Further, this recommendation is supported by the high prevalence of vitamin D deficiency among postmenopausal women. The prevalence of vitamin D deficiency (serum levels below 50 nmol/l or 20 ng/ml) among younger and older postmenopausal women has been found to be about 50 % in many countries around the world, with the highest prevalence (80 %) in older women with hip fractures.

Osteoporotic Hip Fracture in the Elderly Patients: Physicians' Views

Osteoporotic hip fracture is a major healthcare problem, which is associated with a significant mortality, morbidity and socioeconomic burden in elderly patients (1). Recently, this type of fracture affects about 20,000 adults annually in Korea (2). The incidence in 2008 was 139/100,000 men, and 286/100,000 women (3). The residual lifetime risk of osteoporosis-related fracture for individuals over age 50 was 23.8% in men and 59.5% in women. That risk of osteoporotic hip fracture was 5.3% in men and 12.3% in women (2,3). These rates in Korea are compatible with those in Japan; 5.6% in men and 20.0% in women (4). Unlike other developed countries (5), the incidence of osteoporotic hip fracture seems to increase in Korea (6). Usually, the initial care of the hip fracture starts with a medical evaluation at the emergency room. Hip fractures almost always require a surgical intervention, which should be performed as early as possible, because delayed surgery is associated with excess mortality and prolonged hospitalization. However, a cautious medical evaluation and immediate clearance should be performed to reduce perioperative complications. Internal fixation and hip replacement arthroplasty are common surgical treatments. The proportion of hip replacement arthroplasty increased while that of internal fixation decreased annually during the 5 yr in Korea. The surgery usually is followed by a comprehensive multidisciplinary management including rehabilitation and/or nursing home care. Pneumonia, urinary tract infection, and sore develop in more than 20% of patients after a hip fracture operation. To prevent these complications, the patients should ambulate as early as possible after the operation. The risk of complications increases especially in patients who have predisposing factors such as old age, malignancy, and previous history of venous thromboembolism. Additionally, venous thromboembolism is a life-threatening complication. In western countries, this complication is a common cause of death and medical prophylaxis is routinely recommended. However, the medication frequently causes a serious bleeding and infection. Korean patients have a low incidence of symptomatic venous thromboembolism and quite a few fatal pulmonary embolism. Thus, medical thromboprophylaxis should be done cautiously in patients at risk. In most patients, mechanical prophylaxis using intermittent pneumatic compression can prevent venous thromboembolism (7). Delirium is another frequent complication affecting 20% to 30% of elderly patients after hip fracture surgery (8), which is frequently undetected in clinical practice. The rate of non-detection ranges from 30% to 60%. Delirium may have serious consequences for the patient and the family members if not promptly diagnosed and treated. It is frequently prolonged or persistent, resulting in increased morbidity and mortality. Therefore, an early diagnosis by close monitoring and prompt treatment should be performed to reduce hospital stay and cost. Sufficient pain management is important to decrease the risk of delirium as well as to encourage early ambulation. About 50% of senile patients, who experience a hip fracture, will have a second fracture within 3 to 5 yr. Immediate initiation of osteoporosis treatment and educational program decrease the risk of subsequent fracture. Therefore, osteoporosis treatment is important even after hip fracture treatment. However, only 25% to 33% of patients are prescribed for osteoporosis treatment after the first hip fracture. Internationally, a comprehensive systematic approach has been suggested to prevent the secondary fracture (9, 10). Physicians should check vitamin D-25 level and dual-energy X-ray absorptiometry (DXA) if these tests were not done in the last 2 yr. If the patient has osteoporosis, start the osteoporosis treatment immediately. Physicians should check and modify medications, which can make a patient more prone to falls, and discuss environmental modifications of poor lighting and trip hazards at home with patients and their family members. Although an interest on the secondary prevention has been increased in Korea (11), the preventive programs are not been activated well yet. The 30-day mortality rate after hip fracture surgery is about 10%. Approximately 15% of patients die within 6 months and 20% within 1 yr, which are about 3.5 fold higher compared with those of general population (6). Moreover, the mortality rate increases far much higher, if the patient already had medical comorbidities or has postoperative complications. In conclusion, Korean populations are rapidly aging and osteoporotic hip fractures are projected to increase drastically. Osteoporotic hip fracture appears as a significant public health problem with serious socioeconomic burden. Physicians should aware that a comprehensive approach reduces incidence, morbidity and mortality of hip fractures.

Association between modifiable lifestyle factors and residual lifetime risk of diabetes

Background and aimsWhile clinical trials have reported beneficial effects of diet, exercise, and weight loss on incident diabetes in subjects with obesity or impaired glucose tolerance, little is known about the incremental benefit of not smoking and moderate drinking on diabetes risk. We sought to examine the association between modifiable lifestyle factors and residual lifetime risk of diabetes. Methods and ResultsProspective cohorts involving 20,915 men (1982–2008) and 36,594 women (1992–2008). Modifiable lifestyle factors and adiposity were ascertained at baseline in each cohort and incident diabetes was ascertained during follow up. The mean age at baseline was 53.5 y in men and 54.6 y in women. During an average follow up of 22.6 y in men and 13.0 y in women, 2096 men and 2390 women developed diabetes. At age 45 y, the residual lifetime risk of diabetes (95% CI) for men with 0, 1, 2, 3, and 4 + healthy lifestyle factors was 30.5 (27.3–33.7); 21.5 (19.9–23.0); 15.1 (13.9–16.3); 10.3 (9.1–11.5); and 7.3 (5.7–8.9) percent; respectively. Corresponding values for women were 31.4 (28.3–34.5); 24.1 (21.8–26.5); 14.2 (12.7–15.7); 11.6 (9.7–13.5); and 6.4 (4.2–8.6) percent, respectively. ConclusionsThese data show an inverse and graded relation between desirable lifestyle factors and residual lifetime risk of diabetes in men and women. Not smoking and moderate drinking may have additional benefits when added to exercise, weight control, and diet.

The incidence and residual lifetime risk of osteoporosis-related fractures in Korea

Although the Korean population does not have high risk for osteoporosis, the numbers of osteoporosis-related fractures represent a considerable economic burden to society. The purpose of this study was to determine the incidence and residual lifetime risk of osteoporosis-related fractures in Korea, using data from the Health Insurance Review and Assessment Service (HIRA), which includes nationwide information compiled by the Korean government. All new visits or admissions to Korean clinics or hospitals for fractures were recorded prospectively in a nationwide cohort by the Korean HIRA using the International Classification of Diseases, 10th revision, codes and procedure codes. These data were retrospectively evaluated to determine the incidence and residual lifetime risk of osteoporosis-related fractures (hip, spine, distal radius, and humerus fractures), in men and women aged 50 years or more between 2005 and 2008. The annual incidences of osteoporosis-related fractures were 1,661, 1,646, 1,623, and 1,614 per 100,000 person-years in men and women aged 50 years or more from the year 2005 to 2008. The annual incidence of osteoporosis-related fracture in women was three times that of men. The incidence of osteoporosis-related fractures increased with advancing age. In Korea, at the age of 50 years, the residual lifetime probabilities of osteoporosis-related fractures are 59.5% for women and 23.8% for men. This study presents the baseline data for treatment and research on osteoporosis and provides an estimate of osteoporosis-related fractures in Korea.

Hip Fracture in Men-Survival and Subsequent Fractures: A Cohort Study with 22-Year Follow-Up

To evaluate the influence of age on survival and risk of subsequent fracture in men with hip fracture, applying a residual lifetime perspective. Retrospective cohort study with 22-year follow-up. Skåne University Hospital, Malmö, Sweden. Men aged 60 and older (N = 226) with an index hip fracture during 1984/85. Twenty-two-year survival (mortality) and risk of new fractures evaluated in 5-year age bands and age groups (<75, 75-84, ≥ 85). Mean age was 78 ± 9. Mortality at 22 years was 98%. Survivors were all younger than 75 at inclusion. Mortality was dependent on age at all time points (18%, 38%, 69% at 1 year, increasing to 71%, 93%, 100% by 10 years in <75, 75-84, ≥ 85, respectively). Median survival was 5.4 years, 2.0 years, and 3 months, respectively, in these age groups, and 33%, 27%, and 13% of each age-group sustained subsequent fractures, generally within 5 years. Overall 10-year fracture risk was 29% (95% confidence interval (CI)=19-38%), increasing to 44% (95% CI=30-58%) when adjusted for mortality. Residual lifetime risk of new fracture was 33% (95% CI=23-43%), and mortality-adjusted risk was 63% (95% CI=45-81%). Participants younger than 75 at index hip fracture were at greatest risk of new fracture (hazard ratio=2.7, 95% CI=1.1-6.4, P=.03). Almost one-third of men with hip fracture have subsequent fractures during their remaining lifetime. Time at risk is highly dependent on age. Most new fractures occur in relatively younger men and within 5 years, whereas most aged 75 and older die before experiencing a new fracture.