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1.  Relationships Between Selected Gene Polymorphisms and Blood Pressure Sensitivity to Weight Loss in Elderly Persons With Hypertension 
Hypertension  2013;61(4):857-863.
Salt sensitivity, the heterogeneity in the response of blood pressure (BP) to alterations in sodium intake, has been studied extensively, whereas weight sensitivity, the heterogeneity in BP response to weight change, has received scant attention. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes mellitus, or obesity, with weight sensitivity in the Trial of Nonpharmacologic Interventions in the Elderly, where participants with hypertension were randomized to receive intensive dietary intervention of sodium reduction, weight loss, both, or attention control, whereas pharmacological therapy was kept constant. After correcting for multiplicity, we identified significant associations of 3 polymorphisms with weight sensitivity of systolic BP (rs4646994, rs2820037, and rs1800629) and 3 polymorphisms for diastolic BP (rs4646994, rs2820037, and rs5744292). A recursive partitioning algorithm selected the combination of rs4646994, rs1800629, rs1982073, and rs1800896 as the set associated with the highest weight sensitivity. Polymorphisms related to hypertension, obesity, and diabetes mellitus are associated with weight sensitivity of BP.
PMCID: PMC4636329  PMID: 23438931
blood pressure; genetics; obesity; sodium
2.  Comprehensive Stroke Centers May Be Associated With Improved Survival in Hemorrhagic Stroke 
Comprehensive stroke centers (CSCs) provide a full spectrum of neurological and neurosurgical services to treat complex stroke patients. CSCs have been shown to improve clinical outcomes and mitigate disparities in ischemic stroke patients. It is believed that CSCs also improve outcomes in hemorrhagic stroke.
Methods and Results
We used the Myocardial Infarction Data Acquisition System (MIDAS) database, which includes data on patients discharged with a primary diagnosis of intracerebral hemorrhage (ICH; International Classification of Diseases, Ninth Revision [ICD-9] 431) and subarachnoid hemorrhage (SAH; ICD-9 430) from all nonfederal acute care hospitals in New Jersey (NJ) between 1996 and 2012. Out-of-hospital deaths were assessed by matching MIDAS records with NJ death registration files. The primary outcome variable was 90-day all-cause mortality. The primary independent variable was CSC versus primary stroke center (PSC) and nonstroke center (NSC) admission. Multivariate logistic models were used to measure the effects of available covariates. Overall, 36 981 patients were admitted with a primary diagnosis of ICH or SAH during the study period, of which 40% were admitted to a CSC. Patients admitted to CSCs were more likely to have neurosurgical or endovascular interventions than those admitted to a PSC/NSC (18.9% vs. 4.7%; P<0.0001). CSC admission was associated with lower adjusted 90-day mortality (35.0% vs. 40.3%; odds ratio, 0.93; 95% confidence interval, 0.89 to 0.97) for hemorrhagic stroke. This was particularly true for those admitted with SAH.
Hemorrhagic stroke patients admitted to CSCs are more likely to receive neurosurgical and endovascular treatments and be alive at 90 days than patients admitted to other hospitals.
PMCID: PMC4599399  PMID: 25950185
comprehensive stroke center; intracerebral hemorrhage; subarachnoid hemorrhage
3.  Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms 
Breast cancer is a common diagnosis in women. Breast radiation has become critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation-induced heart disease (RIHD) comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation.
PMCID: PMC4332338  PMID: 25741474
breast cancer; radiation side effects; radiation therapy; radiation fibrosis
4.  The Effect of Hurricane Sandy on Cardiovascular Events in New Jersey 
Hurricane Sandy made landfall in New Jersey (NJ) on October 29, 2012. We studied the impact of this extreme weather event on the incidence of, and 30‐day mortality from, cardiovascular (CV) events (CVEs), including myocardial infarctions (MI) and strokes, in NJ.
Methods and Results
Data were obtained from the MI data acquisition system (MIDAS), a database of all inpatient hospital discharges with CV diagnoses in NJ, including death certificates. Patients were grouped by their county of residence, and each county was categorized as either high‐ (41.5% of the NJ population) or low‐impact area based on data from the Federal Emergency Management Agency and other sources. We utilized Poisson regression comparing the 2 weeks following Sandy landfall with the same weeks from the 5 previous years. In addition, we used CVE data from the 2 weeks previous in each year as to adjust for yearly changes. In the high‐impact area, MI incidence increased by 22%, compared to previous years (attributable rate ratio [ARR], 1.22; 95% confidence interval [CI], 1.16, 1.28), with a 31% increase in 30‐day mortality (ARR, 1.31; 95% CI, 1.22, 1.41). The incidence of stroke increased by 7% (ARR, 1.07; 95% CI, 1.03, 1.11), with no significant change in 30‐day stroke mortality. There were no changes in incidence or 30‐day mortality of MI or stroke in the low‐impact area.
In the 2 weeks following Hurricane Sandy, there were increases in the incidence of, and 30‐day mortality from, MI and in the incidence of stroke.
PMCID: PMC4338729  PMID: 25488295
cardiovascular diseases; epidemiology; myocardial Infarction; stroke
5.  The triggering of myocardial infarction by fine particles is enhanced when particles are enriched in secondary species 
Environmental science & technology  2013;47(16):10.1021/es4027248.
Previous studies have reported an increased risk of myocardial infarction (MI) associated with acute increases in PM concentration. Recently, we reported that MI/fine particle (PM2.5) associations may be limited to transmural infarctions. In this study, we retained data on hospital discharges with a primary diagnosis of acute myocardial infarction (using International Classification of Diseases 9th Revision [ICD-9] codes), for those admitted January 1, 2004 to December 31, 2006, who were ≥18 years of age, and were residents of New Jersey at the time of their MI. We excluded MI with a diagnosis of a previous MI and MI coded as a subendocardial infarction, leaving n=1563 transmural infarctions available for analysis. We coupled these health data with PM2.5 species concentrations predicted by the Community Multiscale Air Quality chemical transport model, ambient PM2.5 concentrations, and used the same case-crossover methods to evaluate whether the relative odds of transmural MI associated with increased PM2.5 concentration is modified by the PM2.5 composition/mixture (i.e. mass fractions of sulfate, nitrate, elemental carbon, organic carbon, and ammonium). We found the largest relative odds estimates on the days with the highest tertile of sulfate mass fraction (OR=1.13; 95% CI = 1.00, 1.27), nitrate mass fraction (OR=1.18; 95% CI = 0.98, 1.35), and ammonium mass fraction (OR=1.13; 95% CI = 1.00 1.28), and the lowest tertile of EC mass fraction (OR=1.17; 95% CI = 1.03, 1.34). Air pollution mixtures on these days were enhanced in pollutants formed through atmospheric chemistry (i.e., secondary PM2.5) and depleted in primary pollutants (e.g., EC). When mixtures were laden with secondary PM species (sulfate, nitrate, and/or organics) we observed larger relative odds of myocardial infarction associated with increased PM2.5 concentrations. Further work is needed to confirm these findings and examine which secondary PM2.5 component(s) is/are responsible for an acute MI response.
PMCID: PMC3856764  PMID: 23819750
6.  Cardiopulmonary bypass has a modest association with cancer progression: a retrospective cohort study 
BMC Cancer  2013;13:519.
Given their frequency of occurrence in the United States, cancer and heart disease often coexist. For patients requiring open-heart surgery, this raises concern that the use of cardiopulmonary bypass (CPB) may cause a transient immunosuppression with the potential to promote the spread and growth of coexisting cancer cells. This study examined the association of cardiopulmonary bypass with cancer progression in a large population-based setting using linked data from several state-wide registries.
A retrospective cohort study of cancer risk, stage, and mortality in 43,347 patients who underwent coronary artery bypass graft (CABG) surgery with and without CPB in New Jersey between 1998–2004 was conducted. A competing risk analogue of the Cox proportional hazards model with propensity score adjustment and regression on the cause-specific hazard was used to compute relative risk ratios (95% confidence intervals [CIs]) for patients undergoing CABG surgery with and without CPB.
An increased risk for overall cancer incidence (17%) and cancer-specific mortality (16% overall, 12% case fatality) was observed; yet these results did not reach statistical significance. Of 11 tumor-specific analyses, an increased risk of skin melanoma (1.66 [95% CI, 1.08-2.55: p=0.02]) and lung cancer (1.36 [95% CI, 1.02-1.81: p=0.03]) was observed for patients with pump versus off-pump open-heart surgery. No association was found with cancer stage.
These results suggest that there may be a relationship between CPB and cancer progression. However, if real, the effect is likely modest at most. Further research may still be warranted with particular focus on skin melanoma and lung cancer which had the strongest association with CPB.
PMCID: PMC3831257  PMID: 24180710
Cardiopulmonary bypass; Cancer progression; Population-based cohort study
7.  The Relationship Between Cognitive Function and Physical Performance in Older Women: Results From the Women’s Health Initiative Memory Study 
Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear.
In the Women’s Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change.
Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS—gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p ≤ .01 both). Changes in 3MS and PPM were associated, particularly with chair stands and grip strength (p < .003 both). Baseline PPMs were not associated with subsequent 3MS change.
Baseline global cognitive function and change in global cognitive function were associated with physical performance change, but baseline physical performance was not associated with cognitive change in this cohort. These analyses support the hypothesis that cognitive decline on average precedes or co-occurs with physical performance decline.
PMCID: PMC2822281  PMID: 19789197
Cognitive function; Physical performance; Cognition; Physical function
8.  Triggering of Transmural Infarctions, but Not Nontransmural Infarctions, by Ambient Fine Particles 
Environmental Health Perspectives  2010;118(9):1229-1234.
Previous studies have reported increased risk of myocardial infarction (MI) after increases in ambient particulate matter (PM) air pollution concentrations in the hours and days before MI onset.
We hypothesized that acute increases in fine PM with aerodynamic diameter ≤ 2.5 μm (PM2.5) may be associated with increased risk of MI and that chronic obstructive pulmonary disease (COPD) and diabetes may increase susceptibility to PM2.5. We also explored whether both transmural and nontransmural infarctions were acutely associated with ambient PM2.5 concentrations.
We studied all hospital admissions from 2004 through 2006 for first acute MI of adult residents of New Jersey who lived within 10 km of a PM2.5 monitoring site (n = 5,864), as well as ambient measurements of PM2.5, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone.
Using a time-stratified case-crossover design and conditional logistic regression showed that each interquartile-range increase in PM2.5 concentration (10.8 μg/m3) in the 24 hr before arriving at the emergency department for MI was not associated with an increased risk of MI overall but was associated with an increased risk of a transmural infarction. We found no association between the same increase in PM2.5 and risk of a nontransmural infarction. Further, subjects with COPD appeared to be particularly susceptible, but those with diabetes were not.
This PM–transmural infarction association is consistent with earlier studies of PM and MI. The lack of association with nontransmural infarction suggests that future studies that investigate the triggering of MI by ambient PM2.5 concentrations should be stratified by infarction type.
PMCID: PMC2944082  PMID: 20435544
air pollution; epidemiology; myocardial infarction
9.  Aspirin Use, Dose, and Clinical Outcomes in Postmenopausal Women with Stable Cardiovascular Disease: The Women’s Health Initiative Observational Study 
Despite compelling evidence that aspirin reduces fatal and non-fatal vascular events among the overall population in various settings, women have frequently been underrepresented and their data underreported. We sought to evaluate the relationship between aspirin use, dose (81 or 325mg) and clinical outcomes among postmenopausal women with stable cardiovascular disease.
Women with cardiovascular disease (n=8928) enrolled in the Women’s Health Initiative Observational Study were used for this analysis. The primary outcome was the incidence of all-cause mortality and cardiovascular events (myocardial infarction, stroke and cardiovascular death).
Among 8928 women with stable cardiovascular disease, 4101 (46%) reported taking aspirin, of whom 30% were on 81 and 70% were on 325mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, aspirin use was associated with a significantly lower all-cause (adjusted HR 0.86, [0.75-0.99], P=0.04) and cardiovascular related mortality (adjusted HR 0.75, [0.60-0.95], P=0.01) compared with no aspirin. Aspirin use was associated with a lower risk of cardiovascular events (adjusted HR 0.90, [0.78-1.04], P=0.14) which did not meet statistical significance. Compared with 325mg, use of 81mg was not significantly different for all-cause mortality, cardiovascular events or any individual endpoint.
After multivariate adjustment, aspirin use was associated with significantly lower risk of all-cause mortality, specifically cardiovascular mortality, among postmenopausal women with stable cardiovascular disease. No significant difference was noted between 81 and 325mg of aspirin. Overall, aspirin use was low in this cohort of women with stable cardiovascular disease.
PMCID: PMC2801891  PMID: 20031819
Aspirin; Dose; Women; Cardiovascular Disease; Observational Study
10.  Heart Failure with Preserved and Reduced Left Ventricular Ejection Fraction in ALLHAT 
Circulation  2008;118(22):2259-2267.
Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction [PEF (≥50%) or REF (<50%)]. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42,418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF.
Methods and Results
HF diagnostic criteria were pre-specified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography or radionuclide study was available in 910 (66.6%) of 1367 patients with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case-fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios [HRs] and 95% CIs were 0.69 (0.53-0.91; p=0.009), 0.74 (0.56-0.97; p=0.032), and 0.53 (0.38-0.73; p<0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; HRs were 0.74 (0.59-0.94; p=0.013) and 0.61 (0.47-0.79; p<0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF; HR=1.07 (0.82-1.40; p=0.596). Following HF onset, death occurred in 29.2% of participants (chlorthalidone/amlodipine/lisinopril) with new-onset HFPEF versus 41.9% in those with HFREF, p<0.001 (median follow-up 1.74 years); and in the terminated early chlorthalidone/doxazosin comparison 20.0% (HFPEF) versus 26.0% (HFREF), p=0.185 (median follow-up 1.55 years).
In the ALLHAT trial, using adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF.
PMCID: PMC2775475  PMID: 19001024
antihypertensive therapy; hypertension, detection and control; diuretics; angiotensin-converting enzyme inhibitors; calcium channel blockers; heart failure; ejection fraction
11.  Questionable Hospital Chart Documentation Practices by Physicians 
Journal of General Internal Medicine  2008;23(11):1865-1870.
Physicians, influenced by various pressures, may document information in patient records that they did not personally observe.
To evaluate the hospital chart documentation practices of internists and internal medicine sub-specialists in the Northeastern United States.
An anonymous mail survey questionnaire.
One thousand one hundred twenty-six randomly selected internists and internal medicine sub-specialists.
Responses to questions describing their own hospital chart documentation practices, those they observed among their colleagues, and ratings of the importance of possible influences.
Response rate was 43%. Fifty-nine percent (59%) of physicians reported personally engaging in one or more of six questionable documentation scenarios. Forty percent (40%, CI; 37%-43%) indicated that they recorded laboratory notes in patient records based on information that they did not personally obtain, while 6% (CI; 5%-8%) admitted to writing notes on patients not personally seen or examined. The corresponding percentages reported for their colleagues were 52% (CI; 49%-56%) and 22% (CI; 20%-25%), respectively. Increased rates of documentation lapses were significantly associated with working directly with residents and/or fellows (OR = 1.71, CI; 1.30–2.25), younger age (OR for 10 year age decrease = 1.35, CI; 1.19–1.53), white race (OR = 1.47, CI; 1.08–2.00), and graduation from US medical schools (OR = 1.75, CI; 1.31–2.34).
Most physicians report having engaged in questionable hospital chart documentation. This practice is more common among physicians who are younger, working with house staff, and graduates of US medical schools.
PMCID: PMC2585683  PMID: 18751759
survey research; hospital medicine; medical education-professionalism

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