Is residential exposure to oil refineries a novel contextual risk factor for coronary heart disease?

Despite a multi-decade decrease in cardiovascular disease, geographic disparities have widened, with excess mortality concentrated within the United States (U.S.) South. Petroleum production and refining, a major contributor to climate change, is concentrated within the U.S. South and emits multiple classes of atherogenic pollutants. We investigated whether residential exposure to oil refineries could explain variation in self-reported coronary heart disease (CHD) prevalence among adults in southern states for the year 2018, where the majority of oil refinery activity occurs (Alabama, Mississippi, Louisiana, Arkansas, Texas, New Mexico, and Oklahoma). We examined census tract-level association between oil refineries and CHD prevalence. We used a double matching method to adjust for measured and unmeasured spatial confounders: one-to-n distance matching and one-to-one generalized propensity score matching. Exposure metrics were constructed based on proximity to refineries, activities of refineries, and wind speed/direction. For all census tracts within 10 km of refineries, self-reported CHD prevalence ranged from 1.2% to 17.6%. Compared to census tracts located at ≥5 km and <10 km, one standard deviation increase in the exposure within 5 km of refineries was associated with a 0.33 (95% confidence interval: 0.04, 0.63) percentage point increase in the prevalence. A total of 1119.0 (123.5, 2114.2) prevalent cases or 1.6% (0.2, 3.1) of CHD prevalence in areas within 5 km from refineries were potentially explained by exposure to oil refineries. At the census tract-level, the prevalence of CHD explained by exposure to oil refineries ranged from 0.02% (0.00, 0.05) to 47.4% (5.2, 89.5). Thus, although we cannot rule out potential confounding by other personal risk factors, CHD prevalence was found to be higher in populations living nearer to oil refineries, which may suggest that exposure to oil refineries can increase CHD risk, warranting further investigation.

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. OBJECTIVES: Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. METHODS: Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. RESULTS: Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of HR=1.14-1.44). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with ≤high school education, and workers with body mass index <30 kg/m2. No apparent positive association was observed for the BTEX-H mixture. CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

The burden of coronary heart disease and stroke attributable to dietary cadmium exposure in Chinese adults, 2017.

Cadmium (Cd) is a metal with a long biological half-life that could cause health issues, such as coronary heart disease (CHD), stroke, and other cardiovascular diseases (CVD). Recent studies showed an ascending trend in the dietary Cd intake in the Chinese population. The contribution of dietary Cd intake to CHD and stroke burden, on the other hand, remains to be established. To calculate the disease burden for CHD and stroke attributable to dietary Cd, we estimated dietary Cd intake by associating the Cd concentration in food with consumption frequency. The toxicokinetic (TK) model and dietary Cd consumption were used to simulate urinary cadmium (U-Cd) concentrations. The population attributable fraction (PAF) can be derived for the computation of the attributable disease burden expressed as Disability-Adjusted Life Years (DALYs) in provinces, genders, and age groups by combining the relative risk (RR) with the population distribution of U-Cd. The mean of dietary Cd consumption and the geometric mean of U-Cd in the Chinese adult population are 0.684 µg/kg bw/day and 0.88 µg/g creatinine. The CHD burden attributable to dietary Cd was 3.26 million DALYs, with a 9.69% proportion of the total CHD burden. The DALYs for stroke attributable to Cd in food was approximately 3.64 million, accounting for 8.22% of the overall stroke burden. Furthermore, the attributable disease burden of CHD and stroke are higher in the south, women, and middle-aged and older adults. Our study suggested that foodborne Cd exposure contributes a considerable proportion of the CHD and stroke burden. More attention is needed to control Cd in food in order to reduce the burden of CHD and stroke in the Chinese population.

Whole blood dynamic platelet aggregation counting and 1-year clinical outcomes in patients with coronary heart diseases treated with clopidogrel.

In the setting of coronary heart diseases (CHDs) on treatment with clopidogrel, ADP-induced platelet aggregation has been demonstrated with ischemic events. However, there were very limited data for predicting ischemic events by platelet function test via dynamic platelet aggregation counting (DPAC). The present study aimed to evaluate the relationship between adenosine diphosphate (ADP)-induced whole blood platelet aggregation rates (PARs) and clinical outcomes in patients with CHDs on treatment with clopidogrel. We have retrospectively analyzed the clinical data of consecutive patients with CHDs based on the electronic medical records between May 2016 and December 2018. The primary endpoint was a composite endpoint events (CEEs) of ischemic cardiovascular events (including acute coronary syndrome, heart failure, transient ischemic attack, and cerebral infarction) and all-cause death. A total of 490 patients (mean age 66.6 years, 71% man) were received ADP-induced PARs via DPAC. On follow-up (mean 374 days), 107 subjects (21.8%) developed CEEs. Cox regression analysis indicated that the risk of CEEs was independently associated with ADP-induced whole blood PARs [HR: 1.023, 95% CI: 1.005-1.041, P = .011]. The distribution of CYP2C19 loss of function gene was higher in patients with on-treatment platelet hyperresponsiveness (10/12 vs 38/75, P = .042). In conclusion, ADP-induced whole blood PARs via DPAC is feasible, which can predict the incidence of 1-year CEEs in patients with CHDs on treatment with clopidogrel. CYP2C19 gene polymorphism was associated with clopidogrel on-treatment platelet hyperresponsiveness.

Association of long-term inhalation of caffeine-sodium benzoate with coronary heart disease in men.

OBJECTIVE: A possible correlation between caffeine and coronary heart disease (CHD) is controversial. The objective of this study was to explore the effect of long-term inhalation of caffeine-sodium benzoate (CSB) on the development of CHD in men, the severity of coronary artery lesions and the possible contributing effects of smoking. MATERIALS: A retrospective analysis was performed on 2,001 consecutive men who underwent selective coronary angiography. These men were assigned to a CSB inhalation group (CSB; 1 - 6 times/d, 274 - 1,644 mg/d, > 10 years; n = 326) or a non-inhalation group (non-CSB; n = 1,675). METHODS: The two groups were compared for the prevalence, onset age, and risk factors of CHD. The men were also stratified as CSB-only, smoking-only, combined CSB+ smoking, and the control (non-CSB+non-smoking). The prevalence, onset age, risk factors of CHD, and severity of coronary artery lesions and major adverse cardiovascular events (MACE) were compared among these groups. RESULTS: The prevalence of CHD in the CSB group was higher compared with the non-CSB group (91.72 vs. 86.09%, p < 0.01). In the CSB+smoking group, the percentages of men with CHD (93.11%) or > 70% stenosis of the coronary artery lesion (64.92%) were significantly higher than that of the smoking-only group (88.19 and 54.29%, respectively) or control (83.20 and 52.90%), while the percentage with stenosis involving the anterior descending branch was lower (62.30 vs. 72.29% and 74.17%, p < 0.01). CONCLUSION: Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

Tobacco smoking and risk of all-cause mortality in Indonesia.

Tobacco is well known as a risk factor for early morbidity and mortality worldwide. However, the relative risk of mortality and the effects of smoking vary among the countries. Indonesia, as one of the world's largest market for smoking tobacco, is significantly affected by tobacco-related illness. Previous research has shown that smoking causes several diseases, including stroke, neoplasm and coronary heart disease. There has to date been no research on the hazard risk of smoking for all-cause mortality in Indonesia. This study aimed to identify the association between smoking and all-cause mortality rates in Indonesia. Information from a total of 3,353 respondents aged 40 years and older was collected in this study. The data were taken from the Indonesian Family Life Survey (IFLS) Wave 4 (2007) to collect personal information and determine smoking status and from Wave 5 (2015) to collect information about deaths. Current smokers make up 40.3% of Indonesia's population. Current smokers were more likely to have a higher risk of all-cause death (hazard ratio = 1.48, 95% confidence interval = 1.11 to 1.98) than non-current smokers. The number of smokers in Indonesia remains high and is expected to increase gradually every year. A firm government policy is needed to reduce the number of smokers in Indonesia which would automatically reduce the health problem of smoking-related illness in the future.

A risk-based model to assess environmental justice and coronary heart disease burden from traffic-related air pollutants.

BACKGROUND: Communities need to efficiently estimate the burden from specific pollutants and identify those most at risk to make timely informed policy decisions. We developed a risk-based model to estimate the burden of black carbon (BC) and nitrogen dioxide (NO2) on coronary heart disease (CHD) across environmental justice (EJ) and non-EJ populations in Allegheny County, PA. METHODS: Exposure estimates in census tracts were modeled via land use regression and analyzed in relation to US Census data. Tracts were ranked into quartiles of exposure (Q1-Q4). A risk-based model for estimating the CHD burden attributed to BC and NO2 was developed using county health statistics, census tract level exposure estimates, and quantitative effect estimates available in the literature. RESULTS: For both pollutants, the relative occurrence of EJ tracts (> 20% poverty and/or > 30% non-white minority) in Q2 - Q4 compared to Q1 progressively increased and reached a maximum in Q4. EJ tracts were 4 to 25 times more likely to be in the highest quartile of exposure compared to the lowest quartile for BC and NO2, respectively. Pollutant-specific risk values (mean [95% CI]) for CHD mortality were higher in EJ tracts (5.49 × 10- 5 [5.05 × 10- 5 - 5.92 × 10- 5]; 5.72 × 10- 5 [5.44 × 10- 5 - 6.01 × 10- 5] for BC and NO2, respectively) compared to non-EJ tracts (3.94 × 10- 5 [3.66 × 10- 5 - 4.23 × 10- 5]; 3.49 × 10- 5 [3.27 × 10- 5 - 3.70 × 10- 5] for BC and NO2, respectively). While EJ tracts represented 28% of the county population, they accounted for about 40% of the CHD mortality attributed to each pollutant. EJ tracts are disproportionately skewed toward areas of high exposure and EJ residents bear a greater risk for air pollution-related disease compared to other county residents. CONCLUSIONS: We have combined a risk-based model with spatially resolved long-term exposure estimates to predict CHD burden from air pollution at the census tract level. It provides quantitative estimates of effects that can be used to assess possible health disparities, track temporal changes, and inform timely local community policy decisions. Such an approach can be further expanded to include other pollutants and adverse health endpoints.

Isoflavone Intake and the Risk of Coronary Heart Disease in US Men and Women: Results From 3 Prospective Cohort Studies.

BACKGROUND: Whether soy products confer health benefits related to coronary heart disease (CHD) remains controversial because of inconsistent evidence. METHODS: A total of 74 241 women from the NHS (Nurses' Health Study; 1984-2012), 94 233 women from the NHSII (Nurses' Health Study II; 1991-2013), and 42 226 men from the Health Professionals Follow-Up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline, were included in the present analysis. Dietary data were updated every 2 to 4 years using a validated food frequency questionnaire. Nonfatal myocardial infarction and CHD deaths were adjudicated through reviewing medical records, death certificates, and other medical documents. RESULTS: In these cohorts, 8359 incident CHD cases were documented during 4 826 122 person-years of follow-up. In multivariable-adjusted analyses, isoflavone intake was inversely associated with CHD (pooled hazard ratio [HR] comparing the extreme quintiles: 0.87 [95% CI, 0.81-0.94]; P=0.008). Consumption of tofu, but not soy milk, was inversely associated with the risk of CHD, with pooled HRs (95% CIs) of 0.82 (0.70-0.95; P=0.005) and 0.87 (0.69-1.10; P=0.41), respectively, comparing ≥1 serving/week with <1 serving/month. Further analyses showed that, in women, the favorable association of tofu was primarily driven by stronger inverse association of tofu intake observed in younger women before menopause and postmenopausal women without hormone use (Pinteraction=0.002). CONCLUSIONS: Higher intake of isoflavones and tofu was associated with a moderately lower risk of developing CHD, and in women the favorable association of tofu were more pronounced in young women or postmenopausal women without hormone use.

Exposure to Total Hydrocarbons During Cleanup of the Deepwater Horizon Oil Spill and Risk of Heart Attack Across 5 Years of Follow-up.

Exposure to total hydrocarbons (THC) and volatile organic compounds from air pollution is associated with risk of coronary heart disease. THC exposure from oil spills might be similarly associated, but no research has examined this. We assessed the relationship between THC exposure during the response and cleanup of the Deepwater Horizon oil spill (Gulf of Mexico) and heart attack risk among 24,375 oil spill workers enrolled in the Gulf Long-Term Follow-up Study. There were 312 first heart attacks (self-reported physician-diagnosed myocardial infarction, or fatal coronary heart disease) ascertained during the study period (2010-2016). THC exposures were estimated using a job-exposure matrix incorporating self-reported activities and personal air measurements. We used Cox proportional hazards regression to estimate hazard ratios, with inverse-probability weights to account for confounding and censoring. Maximum THC levels of ≥0.30 parts per million (ppm) were associated with heart attack risk, with a 1.8-fold risk for exposure of ≥3.00 ppm versus <0.30 ppm (hazard ratio = 1.81, 95% confidence interval: 1.11, 2.95). The risk difference for highest versus lowest THC level was 10 excess cases per 1,000 workers. This is the first study of the persistent health impacts of THC exposure during oil spill work, and results support increased protection against oil exposure during cleanup of future spills.

Malignancy and mortality rates in patients with severe psoriatic arthritis requiring tumour-necrosis factor alpha inhibition: results from the British Society for Rheumatology Biologics Register.

Objective: The aim of this study was to compare the incidence of cancer and all-cause and cause-specific mortality rates among a cohort of patients with severe PsA receiving TNF inhibitor (TNFi) with those of the general UK population. Methods: Cancers and deaths were identified from the national cancer and the national death registers in patients with PsA included in the British Society for Rheumatology Biologics Register from start of TNFi until 31 December 2012. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated using published cancer and death rates for the general population. SIRs were calculated for both overall cancer risk and non-melanoma skin cancer. SMRs were calculated for (1) all-cause mortality, (2) death from malignancy and (3) death from circulatory disease. Gender-specific analyses were also performed. Results: Thirty-four cancers and 41 deaths among 709 patients were observed. The risk of malignancy overall was not increased (SIR 0.94; 95% CI: 0.65, 1.34). However, there was a significantly increased incidence of non-melanoma skin cancer (SIR 2.12; 95% CI: 1.19, 3.50). The all-cause mortality rate in our cohort was increased (SMR 1.56; CI: 1.12, 2.11). Death from malignancy was not increased, but death from coronary heart disease was increased (SMR 2.42; 95% CI: 1.11, 4.59). Conclusion: In our cohort of patients with severe PsA, the overall incidence of malignancy was similar to that of the general population, although the incidence of non-melanoma skin cancer was increased. All-cause mortality was significantly increased, in part due to excess of deaths attributed to coronary heart disease.

Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents.

In 1965, the Sugar Research Foundation (SRF) secretly funded a review in the New England Journal of Medicine that discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease (CHD). SRF subsequently funded animal research to evaluate sucrose's CHD risks. The objective of this study was to examine the planning, funding, and internal evaluation of an SRF-funded research project titled "Project 259: Dietary Carbohydrate and Blood Lipids in Germ-Free Rats," led by Dr. W.F.R. Pover at the University of Birmingham, Birmingham, United Kingdom, between 1967 and 1971. A narrative case study method was used to assess SRF Project 259 from 1967 to 1971 based on sugar industry internal documents. Project 259 found a statistically significant decrease in serum triglycerides in germ-free rats fed a high sugar diet compared to conventional rats fed a basic PRM diet (a pelleted diet containing cereal meals, soybean meals, whitefish meal, and dried yeast, fortified with a balanced vitamin supplement and trace element mixture). The results suggested to SRF that gut microbiota have a causal role in carbohydrate-induced hypertriglyceridemia. A study comparing conventional rats fed a high-sugar diet to those fed a high-starch diet suggested that sucrose consumption might be associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans. SRF terminated Project 259 without publishing the results. The sugar industry did not disclose evidence of harm from animal studies that would have (1) strengthened the case that the CHD risk of sucrose is greater than starch and (2) caused sucrose to be scrutinized as a potential carcinogen. The influence of the gut microbiota in the differential effects of sucrose and starch on blood lipids, as well as the influence of carbohydrate quality on beta-glucuronidase and cancer activity, deserve further scrutiny.

Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice.

BACKGROUND: Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) are being developed for several biomedical applications including drug delivery and imaging. However, little is known about their possible adverse effects on thrombosis and cardiac oxidative and DNA damage. METHODS: Presently, we investigated the acute (1 h) effect of intravenously (i.v.) administered USPIO in mice (0.4, 2 and 10 µg/kg). Diesel exhaust particles (DEP; 400 µg/kg) were used as positive control. RESULTS: USPIO induced a prothrombotic effect in pial arterioles and venules in vivo and increased the plasma plasminogen activator inhibitor-1 (PAI-1). Both thrombogenicity and PAI-1 concentration were increased by DEP. The direct addition of USPIO (0.008, 0.04 and 0.2 µg/ml) to untreated mouse blood dose-dependently induced in vitro platelet aggregation. USPIO caused a shortening of activated partial thromboplastin time (aPTT) and prothrombin time (PT). Similarly, DEP administration (1 µg/ml) triggered platelet aggregation in vitro in whole blood. DEP also reduced PT and aPTT. The plasma levels of creatine phosphokinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and troponin-I were increased by USPIO. DEP induced a significant increase of CK-MB, LDH and troponin I levels in plasma. The cardiac levels of markers of oxidative stress including lipid peroxidation, reactive oxygen species and superoxide dismutase activity were increased by USPIO. Moreover, USPIO caused DNA damage in the heart. Likewise, DEP increased the markers of oxidative stress and induced DNA damage in the heart. CONCLUSION: We conclude that acute i.v. administration of USPIO caused thrombosis and cardiac oxidative stress and DNA damage. These findings provide novel insight into the pathophysiological effects of USPIO on cardiovascular homeostasis, and highlight the need for a thorough evaluation of their toxicity.

[Cardiovascular risks of androgen deprivation therapy for prostate cancer]. / Kardiovaskuläre Risiken der Androgendeprivationstherapie beim Prostatakarzinom.

Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. It has increasingly been used in other stages of the disease as well. Besides well-known side effects caused by the lack of testosterone (impotency, osteoporosis, fatigue, loss of muscle mass), an increase of cardiovascular (CV) morbidity and mortality has recently been discussed in association with ADT. Cardiovascular side effects cannot be sufficiently explained by low testosterone levels. This review gives an overview of the recent literature, interprets the results, and offers clinical consequences.

Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due To Combined Estrogen Plus Progestin Therapy.

OBJECTIVE: To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. APPROACH AND RESULTS: Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. CONCLUSIONS: Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Epidemiology of coronary heart disease in HIV-infected versus uninfected individuals in developed countries.

The widespread use of combination antiretroviral therapy (cART) among people living with HIV in developed countries has lead to significantly improved life expectancy. However, extensive use of the effective cART coincides with increasing reports of coronary heart disease (CHD) among people living with HIV, and CHD has become a major cause of death. CHD results from a complex and multifactorial atherosclerotic process involving the over-representation of traditional cardiovascular risk factors, particularly smoking, uncontrolled viral replication, chronic inflammation, immune activation, and exposure to antiretroviral drugs. Consequently careful selection of antiretroviral drugs, cardiovascular risk reduction, and lifestyle modifications are needed. In individuals living with HIV, cardiovascular risk assessment is becoming an important element of care.

Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials.

OBJECTIVES: Five randomized, phase-3 trials demonstrated the efficacy and safety of conjugated estrogens/bazedoxifene (CE/BZA) in treating menopausal symptoms and preserving bone. This pooled analysis of these studies describes the cardiovascular safety of CE/BZA. METHODS: We pooled cardiovascular adjudicated safety data from healthy, non-hysterectomized, postmenopausal women who received ≥ 1 dose of CE 0.45 mg/BZA 20 mg (n = 1585), CE 0.625 mg/BZA 20 mg (n = 1583), any CE/BZA dose (n = 4868), or placebo (n = 1241) for up to 2 years in five trials. Venous thromboembolic events (VTEs), coronary heart disease (CHD), and cerebrovascular events were reviewed by three different independent adjudication committees and summarized using a meta-analytic approach. RESULTS: The rate of VTEs per 1000 woman-years (95% confidence interval, CI) was 0.3 (0.0-2.0) in women taking CE 0.45 mg/BZA 20 mg, 0 (0.0-1.5) in those taking CE 0.625 mg/BZA 20 mg, 0.7 (0.0-1.5) among women taking any CE/BZA dose, and 0.6 (0.0-2.9) with placebo. The incidence of stroke per 1000 woman-years (95% CI) was 0.4 (0.0-2.4), 0.2 (0.0-1.9), 0.44 (0.0-1.1), and 0.0 (0.0-1.7), respectively. The CHD rate per 1000 woman-years was 2.6 (0.0-5.6), 1.4 (0.0-3.9), 2.4 (1.00-3.7) and 2.0 (0.0-5.2). Compared with placebo, relative risk (95% CI) with any CE/BZA dose was 0.5 (0.1-1.8) for VTE, 0.5 (0.1-2.6) for stroke, and 0.63 (0.23-1.74) for CHD. CONCLUSIONS: Up to 2 years of CE 0.45 or CE 0.625 mg with BZA 20 mg had an acceptable cardiovascular safety profile, with rates of stroke and CHD comparable to placebo in healthy postmenopausal women. VTE risk was low.

Postmenopausal hormone therapy and the risks of coronary heart disease, breast cancer, and stroke.

The principal findings are briefly reviewed from the Women's Health Initiative trials of the most commonly used postmenopausal hormone regimens in the United States-conjugated equine estrogens and these same estrogens plus medroxyprogesterone acetate. A more detailed review is presented for three major clinical outcomes: coronary heart disease (CHD), the primary trial outcome for which a major benefit was hypothesized; invasive breast cancer, the primary safety outcome for which some adverse effect was expected; and stroke which surfaced as an important adverse effect with both regimens, and one that is influential in decisions concerning the continued use of postmenopausal estrogens alone. The review for these outcomes includes an update on interactions of treatment effects with study subject characteristics and exposures and with prerandomization biomarker levels. It also includes a focus on timing issues that are important to the understanding of treatment effects. Specifically, with combined estrogen plus progestin, CHD risk was elevated early with the elevation dissipating after a few years of treatment, whereas breast cancer elevations increased during the treatment period, and climbed to about a threefold increase following 5 years of adherence. Importantly, breast cancer risk elevations appear to be higher among women who initiate treatment at the menopause, or soon thereafter, compared with women having a longer gap time. Stroke effects, on the contrary, did not seem to vary appreciably with these timing issues. The adverse effect was evidently localized to ischemic strokes, for which there was an approximate 50% increase with either regimen. The rather limited knowledge concerning the biomarkers and biological pathways that mediate the hormone therapy effects on these diseases is also briefly reviewed.

Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

Risks and benefits of hormone therapy: has medical dogma now been overturned?

BACKGROUND: In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. OBJECTIVES: To evaluate those claims. METHODS: Epidemiological criteria of causation were applied to the evidence. RESULTS: A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. CONCLUSIONS: Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.