Non-fatal Cardiovascular Disease Events Research Articles

252-OR: Cardiorespiratory Fitness Predicts Lower Mortality Rates in Type 2 Diabetes

Look AHEAD was a randomized multi-center clinical trial comparing effects of an intensive lifestyle intervention (ILI) with diabetes support and education (DSE) on CVD events in 5145 adults aged 45-76 years who were overweight or obese and had type 2 diabetes. After 10 years of follow-up, the ILI had no significant effect on the primary outcome of fatal or non-fatal CVD events or on all-cause or CVD mortality rates. We now present a secondary analysis of the effects of cardiovascular fitness at baseline on mortality in 4865 participants. Fitness was defined as the metabolic equivalence (METs) level achieved during maximal workload on a treadmill. For all participants, the mean (SD) were 7.20 (1.97) METs. The all-cause death rate was 14% lower per 1 MET greater fitness at baseline, adjusted for age, sex, race/ethnicity, CVD history, BMI and treatment group (HR 0.86 95% CI 0.80 -0.92). In this model, CVD history (HR 1.82 95% CI 1.42-2.35) but not ILI (HR 0.87 95% CI 0.71-1.07) significantly predicted mortality. Similarly, CVD mortality was 28% lower per 1 MET (HR 0.72, 95% CI 0.62-0.83). Fitness was similarly protective from the other CVD outcomes. The Figure shows all-cause mortality rates modeled by history of CVD, treatment group, age 60 years, and white men not on beta blockers because they were the largest population in the dataset. In conclusion, fitness measured by maximal workload on a treadmill was highly predictive of CVD and mortality. Disclosure A.C. Wills: None. W.C. Knowler: None. J. Curtis: None. M.T. Olaiya: None. Funding National Institutes of Health

Gallstone Disease and the Risk of Cardiovascular Disease

Gallstone disease (GD) is one of the most common presentations to surgical units worldwide and shares several risk factors with cardiovascular disease (CVD). CVD remains the most common cause of death worldwide and results in considerable economic burden. Recent observational studies have demonstrated an association between GD and CVD with some studies demonstrating a stronger association with cholecystectomy. We present the findings of a meta-analysis assessing the relationship between GD and CVD. A total of fourteen cohort studies with over 1.2 million participants were included. The pooled hazard ratio (HR, 95% confidence interval [CI]) for association with GD from a random-effects model is 1.23 (95%CI: 1.16–1.30) for fatal and non-fatal CVD events. The association was present in females and males. Three studies report the relationship between cholecystectomy and CVD with a pooled HR of 1.41 (95%CI: 1.21–1.64) which compares to a HR of 1.30 (95%CI: 1.07–1.58) when cholecystectomy is excluded although confounding may influence this result. Our meta-analysis demonstrates a significant relationship between GD and CVD events which is present in both sexes. Further research is needed to assess the influence of cholecystectomy on this association.

Abstract 146: Evolving Clinical Benefits and Social Value of Lipid Lowering Therapies

Background and Objectives: In 2013-14, approximately 30% of adults (20 years of age or older) in the United States (US) had high low-density lipoprotein cholesterol (LDL-C, LDL-C≥ 200 mg/dL). Elevated LDL-C is associated with an increased risk of cardiovascular disease (CVD) related events and death, and a key target for therapy. The lipid lowering treatment (LLT) landscape has evolved significantly over the course of the last 40 years with the introduction of statins, fibrates, ezetimibe, CETP inhibitors, and PCSK9 inhibitors (PCSK9i). Currently, statins are first-line therapy for LDL-C reduction. This study quantified the effect of LLT use since 1987 on CVD-related mortality and morbidity. Methods: Descriptive analyses of the rates of LLT use and LLT spending over time were conducted using both NHANES (1999-2014) and MEPS data (1996-2016), and the association between LDL-C levels and mortality and hospitalizations were identified in the literature. By using hazard ratios from published clinical trials, and NHANES data on the number of LLT users and frequency of non-fatal CVD events among these users, the total number of non-fatal CVD events prevented over time was calculated. Events avoided were calculated as the difference between CVD events observed among LLT users and events that would have occurred in the absence of LLT use. The latter was calculated using the difference in events between treated and untreated patients in LLT trials. The value associated with the prevention of non-fatal CVD events due to LLT use was calculated as the product of the costs associated with treating CVD events and the total number of CVD events prevented. The value of mortality reduction was calculated as the product of the value of a statistical life year ($150,000) and the life expectancy gain from the WOSCOPS and ODYSSEY clinical trials. This value was compared with LLT spending. Results: The uptake of statins and ezetimibe between 1999 and 2014 prevented an estimated total of 2.8M myocardial infarctions (MIs) and 1.7M strokes in the US. The cumulative value derived from MI and stroke events prevented through statin and ezetimibe use, though largely driven by statin use, from 1999–2012 amounted to approximately $258B (2018 USD) and $37B, respectively. The use of statins from 1999–2012 resulted in an additional 12.6 million life-years at a value of $1.9T, and we estimate that statin use could generate an additional $953.1B in value to society from 2018–2025 through reductions in CVD mortality, with patients retaining 94% of the value. Conclusions: Innovation in the LLT landscape, particularly through the introduction and uptake of statins, ezetimibe and PCSK9is, yields significant value to society through the reduction of costs associated with both fatal and non-fatal CVD events. Of the value that accrues to society from the utilization of statins, patients retain approximately 95%.

Nonfatal and fatal cardiovascular disease events in CPAP compliant obstructive sleep apnea patients

PurposeObstructive sleep apnea (OSA) is suggested to predispose to cardiovascular disease (CVD) events. It is uncertain whether compliance to continuous positive airway pressure (CPAP) treatment could attenuate the risk. We explored this issue in long-term CPAP users and untreated controls.MethodsRetrospective observational cohort of CPAP-treated and control patients were pairwise matched for gender, age, and apnea–hypopnea index (AHI). The study end point was a composite of nonfatal and fatal CVD events. Cox regression model was used to determine the association between CPAP treatment and event-free survival.ResultsA total of 2060 patients (75.8% male, mean age 56.0 ± 10.5 years), of which 76.4% had moderate–severe OSA, were included. In the CPAP-treated group (N = 1030), the median use of CPAP was 6.4 h/day during a median follow-up of 8.7 years. The control group (N = 1030) was followed for a median of 6.2 years after the CPAP treatment had ended. The study end point occurred in 14.4% (N = 148) of the CPAP-treated and in 18.8% (N = 194) of the control patients (p = 0.006). Using the Cox regression model adjusted for gender, age, AHI, body mass index, and history of CVD, hypertension, type 2 diabetes, and chronic obstructive pulmonary disease at baseline, a beneficial association between CPAP treatment and CVD risk was observed (hazard ratio 0.64, confidence interval 95% 0.5–0.8, p < 0.001).ConclusionsCPAP treatment was associated with a decreased risk of nonfatal and fatal CVD events. Majority of the patients were compliant to CPAP. The association was demonstrated independent from common cardiovascular risk factors and AHI.

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.

Abstract 127: Premenopausal Cardiovascular Disease is Associated With Early Natural Menopause

Introduction: Early menopause has been associated with an increased risk of cardiovascular disease (CVD), but few studies have examined the converse, i.e., whether CVD events that occurred before menopause were linked to early natural menopause. Methods: Pooled participant-level data (177 131 women) from nine studies that contributed to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of non-fatal premenopausal CVD events (including coronary heart disease (CHD) and stroke events) and age at natural menopause. Age at menopause was categorised as &lt;45 (early), 45-49, 50-51(reference), 52-53 and ≥54 years. Age at onset of premenopausal CVD events was grouped as &lt;35, 35-39 and ≥40 years. Women who experienced no premenopausal CVD event were used as the reference group. Results: Overall, there were 1561 (0.9%) non-fatal premenopausal CVD events (including 1130 CHD and 469 stroke events). The mean age at onset of premenopausal CVD was 41.3 years (standard deviation: 8.2 years, median 44.0 years). Compared with women without experiencing any premenopausal CVD events, women who experienced premenopausal CVD, CHD or stroke before age 35 years had 2-fold increased risk of experiencing early menopause (&lt;45 years), with adjusted RRR (95%CI) of 1.92 (1.17, 3.14), 1.86 (1.01, 3.43), 2.17 (1.43, 3.30) respectively, whereas women with premenopausal CVD after age 40 years were more likely to experience normal menopause at age around 51 years. The associations remained after adjusting for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension status and family history of CVD. Conclusions: In conclusion, women with premenopausal CVD events that occurred before age 35 years had twice the risk of having early menopause. Shared genetic and environmental factors, as well as compromised vasculature after CVD events may play a role.

Hypertensive pregnancy disorders increase the risk of maternal cardiovascular disease after adjustment for cardiovascular risk factors

Background and aimHypertensive pregnancy disorders are associated with subsequent cardiovascular disease (CVD), but the extent to which this association is explained by shared risk factors is unknown. We aimed to evaluate whether hypertensive pregnancy disorder in first pregnancy is associated with increased subsequent risk of maternal CVD after adjustment for established CVD risk factors measured after pregnancy. Methods and resultsA total of 20,075 women with a first delivery registered in the Medical Birth Registry of Norway (1980–2003) participated in Cohort of Norway (CONOR) health surveys a mean (standard deviation) of 10.7 (5.5) years after delivery. They were then followed (median 11.4 years) for an incident fatal or non-fatal CVD event through linkage to the Cardiovascular Disease in Norway (CVDNOR) database and the Norwegian Cause of Death Registry. Hypertensive pregnancy disorders were associated with an increased risk of CVD [Hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.9–2.8], which remained significant after adjustment for established CVD risk factors including body mass index, smoking, hypertension, diabetes, serum glucose and lipid levels (HR 1.5; 95% CI 1.2–1.8). The population attributable fraction of CVD due to hypertensive pregnancy disorder was 4.3% (95% CI 1.9–6.6) after multivariable adjustment. ConclusionThe association between hypertensive pregnancy disorders and CVD risk was mediated in part by related CVD risk factors measured 10 years following delivery. These results underline the importance of post-pregnancy follow-up of women with hypertensive pregnancy disorders focusing on modifiable, lifestyle related risk factors to prevent future CVD.

Application of Cardiovascular disease (CVD) risk assessment equations to the Thai population

Objective: The objectives of this study are: 1.) To calculate the probability of Cardiovascular Disease (CVD) events by applying three different equations, which are: the Asia-Pacific Cohort Study (APCS) equation, the Framingham-Asia equation and the original Framingham equation, to the individual risk factors data from the NHESIV, Thailand. 2) To estimate the number of 8-10 years CVD events. 3) To validate and identify the most suitable CVD risk equations for the Thai population. The individual risk factors from the NHESIV dataset was entered into a Microsoft Excel spreadsheet as the baseline population. Methods: Asia-Pacific Collaborative Cohort Study (APCCS) equations, the Framingham-Asia equation and the original Framingham equation, are applied to calculate the probability of 8 to 10 years CVD events by age groups and gender. The CVD events in this analysis refer to all fatal and non-fatal CVD events (ICD10, I00-I99), which include Ischemic heart disease (IHD) (ICD10, I20-I25) and stroke (ICD10, I60-I69). Results: The 4th National Health Examination Survey IV 2009 (NHESIV) dataset has been entered into a Microsoft Excel spreadsheet as the baseline population. APCCS, the Framingham-Asia and the original Framingham equations, were applied to the NHESIV dataset. The APCCS equation calculated the average 8-years probability of getting CVD as 8.3% in men and 7.8% in women. The 8-year likelihood of CVD in the Framingham-Asia equation was 7.2% in men and 8.1% in women. The original Framingham equation showed the highest probability of 10-years CVD which were 18.8% in men and 11.1% in women. Conclusions: The original Framingham equation overestimated the risk of CVD in the Thai population in all age groups. The Asia-Pacific Cohort Study (APCCS) and the Framingham-Asia equations, both performed better estimation than the original Framingham equation in both men and women.

The cost-effectiveness of canakinumab for secondary prevention of cardiovascular disease: The Australian healthcare perspective

BackgroundCanakinumab is a fully human monoclonal antibody targeting interleukin-1β. It is currently indicated for use in those with rheumatologic disorders due to its anti-inflammatory properties, and was recently shown to be beneficial for the secondary prevention of cardiovascular disease (CVD). However, the cost-effectiveness of canakinumab used to treat CVD is unknown. MethodsA Markov state transition model was developed and populated with a hypothetical sample of 1000 individuals profiled on the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS); with a history of myocardial infarction (MI) and blood concentrations of high-sensitivity C-reactive protein (hsCRP) of >2 mg/L. With each annual cycle, individuals could have a recurrent non-fatal CVD event (MI or stroke), or die from a CVD event or die from other causes based on data from CANTOS. Individuals continued to cycle through the model for 20 years or until death. Cost and utility data was applied. Outcomes were discounted (5% annually). ResultsOver a 20-year time horizon, canakinumab is predicted to prevent 40 recurrent cardiovascular events and save 287 (discounted) years of life and 239 (discounted) quality-adjusted life years (QALYs) in 1000 individuals. At an annual cost of AUD36,049 (USD25,590, GBP19,662) per person, canakinumab would not be considered cost-effective within the Australian healthcare system, with an incremental cost-effectiveness ratio (ICER) of AUD1,221,170 per QALY gained. ConclusionsCanakinumab is an attractive treatment option to reduce recurrent CVD among patients with high hsCRP. It would be considered cost-effective in this treatment setting within the perspective of the Australian public healthcare system if its annual costs do not exceed AUD1500 (USD1065, GBP818) per person.

Cardiovascular disease-related mortality and factors associated with cardiovascular events in the TREAT Asia HIV Observational Database (TAHOD).

With aging of the HIV-positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD-related and other causes of death (CODs) and factors associated with CVD in a multi-country Asian HIV-positive cohort. Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries. The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.

Primary prevention of cardiovascular disease: an umbrella review.

The aim of this study is to determine the effectiveness of non-pharmacological interventions for prevention of cardiovascular disease (CVD) events and mortality in healthy adults or those at high risk of CVD. An umbrella review about primary prevention of non-pharmacological interventions was undertaken in key databases as PubMed Health, Effective Health Care Program AHRQ, McMaster University and the Cochrane Plus until July 2017. The primary outcomes were the relative risk of fatal and non-fatal CVD events, and mortality. Secondary outcomes were adverse events. Twenty-four reviews were included of which thirteen reported outcomes of interest. Four of these found a pooled statistically significant risk reduction: dietary supplements of vitamin D, increased consumption of omega 3 fatty acids, Qigong, and counselling or education to modify more than one cardiovascular risk factor. Seven studies reported adverse events but minor or insignificant with respect to the control group. Four non-pharmacological interventions have been shown to provide a statistically significant reduction in risk of CVD events or overall mortality, with minor adverse events if any. Further research should aim for higher methodological quality and longer follow-up of interventions to establish if these interventions, alone or in combination, translate into definite long-term health benefits.

Modelling the cost-effectiveness of pay-for-performance in primary care in the UK

BackgroundIntroduced in 2004, the United Kingdom’s (UK) Quality and Outcomes Framework (QOF) is the world’s largest primary-care pay-for-performance programme. Given some evidence of the benefits and the substantial costs associated with the QOF, it remains unclear whether the programme is cost-effective. Therefore, we assessed the cost-effectiveness of continuing versus stopping the QOF.MethodsWe developed a lifetime simulation model to estimate quality-adjusted life years (QALYs) and costs for a UK population cohort aged 40–74 years (n = 27,070,862) exposed to the QOF and for a counterfactual scenario without exposure. Based on a previous retrospective cross-country analysis using data from 1994 to 2010, we assumed the benefits of the QOF to be a change in age-adjusted mortality of −3.68 per 100,000 population (95% confidence interval –8.16 to 0.80). We used cost-effectiveness thresholds of £30,000/QALY, £20,000/QALY and £13,000/QALY to determine the optimal strategy in base-case and sensitivity analyses.ResultsIn the base-case analysis, continuing the QOF increased population-level QALYs and health-care costs yielding an incremental cost-effectiveness ratio (ICER) of £49,362/QALY. The ICER remained >£30,000/QALY in scenarios with and without non-fatal outcomes or increased drug costs, and under differing assumptions about the duration of QOF benefit following its hypothetical discontinuation. The ICER for continuing the programme fell below £30,000/QALY when QOF incentive payments were 36% lower (while preserving QOF mortality benefits), and in scenarios where the QOF resulted in substantial reductions in health-care spending or non-fatal cardiovascular disease events. Continuing the QOF was cost-effective in 18%, 3% and 0% of probabilistic sensitivity analysis iterations using thresholds of £30,000/QALY, £20,000/QALY and £13,000/QALY, respectively.ConclusionsCompared to stopping the QOF and returning all associated incentive payments to the National Health Service, continuing the QOF is not cost-effective. To improve population health efficiently, the UK should redesign the QOF or pursue alternative interventions.

The cost-effectiveness of PCSK9 inhibitors - The Australian healthcare perspective

BackgroundFor patients in whom statins are not tolerated or effective as monotherapy, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid lowering therapies that may reduce low-density lipoprotein cholesterol (LDL-C) levels by up to 50% and lower cardiovascular events. While an important treatment option, the cost-effectiveness of PCSK9i in Australia remains unknown. This study aimed to determine the cost-effectiveness of PCSK9i compared to placebo in the prevention of atherosclerotic cardiovascular disease (CVD). Methods and resultsA Markov cohort state-transition model was developed in Microsoft Excel. A hypothetical sample of 1000 individuals based on subjects in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial populated the model. With each five-year cycle, model subjects could have non-fatal CVD events (myocardial infarction and/or stroke), or die from CVD or other causes. Follow-up was simulated for 25 years. CVD risk reduction, cost and utility data were gathered from published sources. At current acquisition prices (AU$8174 per person per year), the incremental cost effectiveness ratio (ICER) was AU$308,558 per quality-adjusted life year (QALY) saved. Acquisition prices would need to be reduced to approximately AU$1500 per person per annum for PCSK9i to reach the arbitrary cost-effectiveness threshold of AU$50,000 per QALY saved. Conclusion(s)PCSK9i are an effective alternative for those with existing CVD or at high risk of CVD in whom statin therapy alone is ineffective, but are not cost-effective to the Australian healthcare system based on current prices.

Ideal cardiovascular health metrics and its association with 20-year cardiovascular morbidity and mortality in a Chinese population

BackgroundThe American Heart Association (AHA) developed a simplified assessment tool based on seven ideal cardiovascular health (CVH) metrics, but the relationship between the AHA defined ideal CVH metrics and cardiovascular...

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent.

AimsThe data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals.Methods and resultsA total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass.ConclusionIncreasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged. Take home figureThe obesity paradox is mainly due to the effect of confounding on BMI and disappears on other adiposity measures.

Diabetes and number of years of life lost with and without cardiovascular disease: a multi-state homogeneous semi-Markov model.

We quantified the impact of type 2 diabetes on incidence of non-fatal cardiovascular disease (CVD) and mortality, considering CVD as a continuum from occurrence of diabetes to the end point, and estimated the 15-year life expectancy with and without CVD. A total of 7239 Iranian adults (3246 men), aged ≥30years, were followed from 1999 to 2014. We applied a multi-state semi-Markov model with three transitions including CVD-free to non-fatal CVD, CVD-free to death and non-fatal CVD to death, and studied the influence of diabetes on each transition rate, stratifying by sex and adjusting for confounders. Diabetes was significantly associated with increased risk of non-fatal CVD in men [hazard ratio, 1.70 (1.36-3.53)] and women [2.19 (1.74-2.77)], and of all-cause death [2.72 (2.03-3.63) and 1.92 (1.37-2.67) in men and women, respectively]. An increased risk of mortality was found only among diabetic men, when non-fatal CVD was occurred [2.19 (1.36-3.53)]. Men with diabetes experienced first non-fatal CVD and death without CVD 1.7 and 1.4years, respectively, earlier than those without diabetes; the corresponding values were 1.4 and 0.7years for women. Moreover, diabetic men lived 1.3years less than non-diabetic counterparts when non-fatal CVD was occurred. Diabetes increased the risk of non-fatal CVD events and all-cause mortality and consequently decreased the number of years lived without CVD. A decrease in LE was found only among diabetic men compared to non-diabetics after non-fatal CVD occurred.

Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD – A comparative analysis from the KAROLA study

High-sensitivity Troponins (hs-cTnT and hs-cTnI) are established biomarkers to identify patients with an acute myocardial infarction. However, data comparing the capacity of these two subtypes in predicting recurrent cardiovascular disease (CVD) events in a population with stable coronary heart disease (CHD) after adjustment for several other modern biomarkers are lacking. We measured both troponins at baseline in 1068 CHD patients, followed them for 13years, assessed a combined CVD endpoint, and adjusted for multiple traditional and novel risk factors. Both troponins correlated significantly with age, low and high BMI, male gender, statin therapy, and emerging biomarkers (e.g. cystatin C, NT-proBNP, GDF-15, hsCRP or galectin 3). During follow-up of 13years, 267 fatal and non-fatal CVD events occurred. Top quartiles of both troponin concentrations were significantly associated with CVD events compared to the bottom quartile after adjustment for age, gender and established CVD risk factors (hs-cTnT: hazard ratio (HR) 2.54 (95% CI, 1.60-4.03), p for trend: <0.0001; hs-cTnI: HR 2.20 (95% CI, 1.44-3.36), p for trend: <0.0002 and 0.0003). However, after adjustment for other emerging biomarkers, the associations were no longer statistically significant (hs-cTnT: HR 1.63 (95% CI, 0.97-2.73), p for trend: 0.17; hs-cTnI: HR 1.61 (95% CI, 1.00-2.60), p for trend: 0.067). Both troponins are reliable biomarkers of recurrent cardiovascular events, especially if other novel, important markers such as NT-proBNP, GDF-15 and galectin 3 are not available. Nevertheless, a further workup is still needed to explain the complex interaction of biomarkers indicating vascular and myocardial function.

The relation between gallstone disease and cardiovascular disease

Gallstone disease (GD) is a common digestive disorder that shares many risk factors with cardiovascular disease (CVD). CVD is an important public health issue that encompasses a large percentage of overall mortality. Several recent studies have suggested an association between GD and CVD, while others have not. In this report, we present a meta-analysis of cohort studies to assess the association between GD and CVD. We included eight studies published from 1980 to 2017, including nearly one million participants. The pooled relative risk (RR, 95% confidence interval [CI]) from the random-effects model associates with GD is 1.23 (95% CI: 1.17–1.30) for fatal and nonfatal CVD events. The pooled RR from the random-effects model of CVD events in female patients with GD is 1.24 (95% CI: 1.16–1.32). In male GD patients, the pooled RR from the random-effects model for CVD is 1.18 (95% CI: 1.06–1.31). Our meta-analysis demonstrates a substantially increased risk of fatal and nonfatal CVD events among patients with a medical history of GD. We suggest that interested investigators should further pursue the subject. In addition, both male and female patients with GD have a risk of CVD, and women have a higher risk than men.

Risk of cardiovascular disease among women with endometrial cancer compared to cancer-free women in the Women’s Health Initiative

BackgroundThe majority of women diagnosed with endometrial cancer (EC) have low cancer-specific mortality; however, a high prevalence of cardiovascular disease (CVD) risk factors places EC patients at high risk of developing CVD. In the Women’s Health Initiative (WHI), we assessed the hypothesis that CVD risk was higher among women who developed EC compared with women who did not develop EC. MethodsWe compared the incidence of fatal and non-fatal CVD events among 1,179 women who developed Type I EC, 211 women who developed Type II EC, and 92,217 women who did not develop EC. We first estimated univariable cause-specific hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association between an EC diagnosis (overall and by EC type) with CVD risk using Cox proportional hazards regression. Potential confounders were examined using a risk factor modeling approach; final multivariable-adjusted models included covariates that changed univariable CHRs for EC diagnosis by≥5%. ResultsIn multivariable-adjusted models, CVD risk did not significantly differ between women who developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87–1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98, 95% CI=0.84–1.14); however, there was a positive but statistically nonsignificant association for Type II EC (CHR=1.32, 95% CI=0.88–1.97). ConclusionDespite our null findings, women with EC should still receive counseling and support to make lifestyle changes aimed at reducing weight as appropriate, given the high prevalence of CVD risk factors at diagnosis.