Male survivors of allogeneic hematopoietic stem cell transplantation have a long term persisting risk of cardiovascular events.
ABSTRACT: Long-term survivors of allogeneic stem cell transplantation (SCT) have increased risk of cardiovascular disease. We retrospectively studied cardiovascular risk factors (CVRFs) in 109 SCT survivors (62 males, 47 females; median age 34 years) five years or more after bone marrow (15) or T cell-depleted peripheral blood (94) SCT for CML (56), acute leukemia (29), MDS (13), and others (11). One death and two cardiovascular events were reported. At five and ten years after SCT, respectively, 44% and 52% had abnormal lipid profiles; 23% of 5-year survivors met the Adult Treatment Panel III threshold for dyslipidemia treatment, which is substantially higher than the age-matched general population. There were significant increases in prevalence of hypertension (p < 0.001), diabetes (p = 0.018), and body mass index (p = 0.044) after SCT compared with baseline. The Framingham general cardiovascular risk score (FGCRS) in males at five years after SCT projected a doubling (median 10.4% vs. 5.4%) in the 10-year risk of cardiovascular events. Females received HRT after SCT, and none had increased FGCRS. Chronic GVHD and C-reactive protein were not associated with CVRF at any time. All CVRFs stabilized between five and ten years after SCT. Thus, SCT survivors have sustained elevations in CVRFs. Males have a significantly increased risk of cardiovascular events in their second and third decade after SCT.
Project description:BACKGROUND:Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities). METHODS:We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10?559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models. RESULTS:The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls >15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs. CONCLUSIONS:AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis.
Project description:Hematopoietic cell transplantation (HCT) recipients may be at an increased risk of developing hypertension, diabetes, and dyslipidemia (referred to as cardiovascular risk factors [CVRFs]); and these factors can potentially increase the risk of cardiovascular disease (CVD). We examined the incidence and predictors of CVRFs and subsequent CVD in 1885 consecutive 1+year survivors of HCT performed at City of Hope between 1995 and 2004. Ten-year cumulative incidence of hypertension, diabetes, dyslipidemia, and multiple (? 2) CVRFs was 37.7%, 18.1%, 46.7%, and 31.4%, respectively. The prevalence of CVRFs was significantly higher among HCT recipients compared with the general population; contributed to largely by allogeneic HCT recipients. Older age and obesity at HCT were associated with increased risk of CVRFs. History of grade II-IV acute graft versus host disease was associated with an increased risk for hypertension (relative risk [RR] = 9.1, P < .01), diabetes (RR = 5.8, P < .01), and dyslipidemia (RR = 3.2, P < .01); conditioning with total body irradiation was associated with an increased risk of diabetes (RR = 1.5, P = .01) and dyslipidemia (RR = 1.4, P < .01). There was an incremental increase in 10-year incidence of CVD by number of CVRFs (4.7% [none], 7.0% [1 CVRF], 11.2% [? 2 CVRFs], P < .01); the risk was especially high (15.0%) in patients with multiple CVRFs and pre-HCT exposure to anthracyclines or chest radiation.
Project description:To examine the relationship between cardiovascular risk factors (CVRFs) and cognitive performance in a multiethnic sample of older adults.We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project. A composite score including smoking, stroke, heart disease, diabetes, hypertension, and central obesity represented CVRFs. Multiple group parallel process multivariate random effects regression models were used to model cognitive functioning and examine the contribution of CVRFs to baseline performance and change in general cognitive processing, memory, and executive functioning.Presence of each CVRF was associated with a 0.1 SD lower score in general cognitive processing, memory, and executive functioning in black and Hispanic participants relative to whites. Baseline CVRFs were associated with poorer baseline cognitive performances among black women and Hispanic men. CVRF increase was related to baseline cognitive performance only among Hispanics. CVRFs were not related to cognitive decline. After adjustment for medications, CVRFs were not associated with cognition in Hispanic participants.CVRFs are associated with poorer cognitive functioning, but not cognitive decline, among minority older adults. These relationships vary by gender and medication use. Consideration of unique racial, ethnic, and cultural factors is needed when examining relationships between CVRFs and cognition.
Project description:BACKGROUND:Cardiovascular disease (CVD) is a heavy burden on cancer patients worldwide. This study aimed to evaluate the prevalence and influence of cardiovascular risk factors (CVRF) and CVD on the all-cause mortality among Chinese cancer patients. RESULTS:Overall, 13.0% of all cancer patients had at least one type of CVRFs and 5.0% with CVDs. Patients with CVRF or CVD presented more frequently at later stages and received higher percentage of oncotherapy. During 1,782,527 person-years of follow-up, the all-cause mortality in cancer patients with CVDs and with CVRFs was higher compared with those without (182.6/1000, 109.5/1000 and 93.3/1000 person-years, respectively). Cox regression analysis showed that patients with heart failure (HR 1.79, 95% CI 1.61-1.99), myocardial infarction (HR 1.50, 95% CI 1.16-1.95), atrial fibrillation (HR 1.30, 95% CI 1.09-1.53), stroke (HR 1.21, 95% CI 1.11-1.32), hypertension (HR 1.10, 95% CI 1.04-1.16) and diabetes (HR 1.16, 95% CI 1.08-1.24) had increased all-cause mortality, whereas dyslipidemia patients had better prognosis (HR 0.73, 95% CI 0.64-0.83). Stratified by cancer type, the prognostic impact of specific CVRF or CVD varied. METHODS:We consecutively recruited 710,170 cancer patients between Feb. 1995 and Jun. 2018. A stratified Cox proportional hazards model was used to analyze the effect of comorbidities on the overall survival of patients stratified by cancer type. CONCLUSIONS:Cancer patients are vulnerable to comorbidity related to heart and cerebral disease. The influence of comorbidities on prognosis is noticeable and specific both for the type of cancer and comorbidities.
Project description:BACKGROUND:Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. METHODS AND RESULTS:In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol. CONCLUSIONS:Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.
Project description:OBJECTIVE:Although emerging evidence indicates that increased variability in cardiovascular risk factors (CVRFs) among populations at midlife or later is a reliable predictor of adverse health outcomes, it is unknown whether intraindividual CVRF variability during childhood or adolescence is an independent predictor of later-life diabetes. We aimed to examine the association of CVRF variability during childhood with diabetes in later life. RESEARCH DESIGN AND METHODS:We included 1,718 participants who participated in the Bogalusa Heart Study and had measures at least four times during childhood (aged 4-19 years). The mean follow-up period was 20.5 years. Intraindividual CVRF variabilities during childhood were calculated using SD, coefficient of variation, deviation from age-predicted values, and residual SD based upon four to eight serial measurements in childhood. RESULTS:Increased variability in BMI or HDL cholesterol (HDL-C) during childhood, irrespective of the indices used, was significantly positively associated with later-life diabetes risk independent of their respective mean levels in childhood and other possible confounding factors. In combined analysis, the magnitude of the association with diabetes risk was similar for high childhood BMI variability and high childhood HDL-C variability. After adjustments for potential confounding variables, other CVRF variabilities including systolic/diastolic blood pressure, total cholesterol, triglycerides, and LDL cholesterol were not significantly associated with diabetes. CONCLUSIONS:Increased BMI and HDL-C variabilities during childhood were significant risk factors for the development of diabetes independently of diverse risk factors, which may offer new insights into the childhood origin of adult-onset diabetes.
Project description:Little is known regarding the effects of environmental lead exposure on cardiovascular risk factors in the adolescent population. We studied 11,662 subjects included in the National Health and Nutrition Examination Survey (NHANES) 1999-2012. Blood lead levels were analysed for their association with cardiovascular risk factors (CVRF). Regression coefficients (Beta) and 95% confidence intervals (CIs) of blood lead in association with CVRF (e.g., total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure) were estimated using multivariate and generalized linear regression after adjusting for age, gender, ethnicity, serum cotinine, body mass index (BMI), physical activity, and household income. We identified a strong positive association between blood lead (coefficient?=?0.022, 95% CI 0.003, 0.041; P?=?0.022) and LDL-cholesterol in adolescents (age 12-19 years). However, no associations with other CVRFs were found in the overall population. In the generalized linear models, participants with the highest lead levels demonstrated a 1.87% (95% CI 0.73%, 3.02%) greater increase in serum LDL-cholesterol (p for trend?=?0.031) when compared to participants with the lowest lead levels. These results provide epidemiological evidence that low levels of blood lead are positively associated with LDL-cholesterol in the adolescent population.
Project description:BACKGROUND:In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs. METHODS:SAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200?mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects. RESULTS:In this pooled analysis, a total of 4439 patients received ?1 dose of study drug. A total of 3500 patients (78.8%) had ?1 CVRF, and 1833 patients (41.3%) had ?2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2?h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ?1, ? 2, ? 3, or???4 CVRFs was palpitations. CONCLUSIONS:When analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION:ClinicalTrials.gov NCT02439320 (SAMURAI), registered 18 March 2015 and ClinicalTrials.gov NCT02605174 (SPARTAN), registered 11 November 2015.
Project description:Background: The brain atrophy and lesion index (BALI) has been developed to assess whole-brain structural deficits that are commonly seen on magnetic resonance imaging (MRI) in aging. It is unclear whether such changes can be detected at younger ages and how they might relate to other exposures. Here, we investigate how BALI scores, and the subcategories that make the total score, compare across adulthood and whether they are related to the level of cardiovascular risks, in both young and old adulthood. Methods: Data were from 229 subjects (72% men; 24-80 years of age) whose annual health evaluation included a routine anatomical MRI examination. A BALI score was generated for each subject from T2-weighted MRI. Differences in the BALI total score and categorical subscores were examined by age and by the level of cardiovascular risk factors (CVRFs). Regression analysis was used to evaluate relationships between continuous variables. Relative risk ratios (RRRs) of CVRF on BALI were examined using a multinomial logistic regression. The area under the receiver operating characteristic (ROC) curve was used to estimate the classification accuracy. Results: Nearly 90% of the participants had at least one CVRF. Mean CVRF scores increased with age (slope = 0.03; r = 0.36, 95% confidence intervals: 0.23-0.48; p < 0.001). The BALI total score was closely related to age (slope = 0.18; r = 0.69, 95% confidence intervals: 0.59-0.78; p < 0.001), as so were the categorical subscores (r's = 0.41-0.61, p < 0.001); each differed by the number of CVRF (t-test: 4.16-14.83, ? 2: 6.9-43.9, p's < 0.050). Multivariate analyses adjusted for age and sex suggested an independent impact of age and the CVRF on the BALI score (for each year of advanced age, RRR = 1.20, 95% CI = 1.11-1.29; for each additional CVRF, RRR = 3.63, 95% CI = 2.12-6.23). The CVRF and BALI association remained significant even in younger adults. Conclusion: The accumulation of MRI-detectable structural brain deficits can be evident from young adulthood. Age and the number of CVFR are independently associated with BALI score. Further research is needed to understand the extent to which other age-related health deficits can increase the risk of abnormalities in brain structure and function, and how these, with BALI scores, relate to cognition.
Project description:We aimed to describe diagnosed acute coronary syndrome (ACS) and its care management and outcomes in emergency departments (EDs) and to determine related cardiovascular risk factors (CVRFs). We conducted a cross sectional multicenter study that included 1173 adults admitted to EDs for acute chest pain (ACP) in 2015 at 14 sites in Tunisia. Data included patients' baseline characteristics, diagnosis, treatment and output. ACS represented 49.7% of non-traumatic chest pain [95% CI: 46.7-52.6]; 74.2% of ACS cases were unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI). Males represented 67.4% of patients with ACS (p?<?0.001). The median age was 60?years (IQR 52-70). Emergency medical service transportation was used in 11.9% of cases. The median duration between chest pain onset and ED arrival was two hours (Inter quartile ranges (IQR) 2-4?h). The age-standardized prevalence rate was 69.9/100,000 PY; the rate was 96.24 in men and 43.7 in women. In the multivariable analysis, CVRFs related to ST segment elevation myocardial infarction were age correlated to sex and active smoking. CVRFs related to UA/NSTEMI were age correlated to sex, familial and personal vascular history and type 2 diabetes. We reported 27 cases of major adverse cardiovascular events (20.0%) in patients with STEMI and 36 in patients with UA/NSTEMI (9.1%). Half of the patients consulting EDs with ACP had ACS. Emergency medical service transportation calls were rare. Management delays were acceptable. The risk of developing an UA/NSTEMI was equal to the number of CVRFs +?1. To improve patient outcomes, it is necessary to increase adherence to international management guidelines.