Marty S. Player

Anxiety Disorders, Hypertension, and Cardiovascular Risk: A Review

Hypertension, coronary heart disease (CHD), and anxiety disorders all cause substantial morbidity to patients and costs to the healthcare system. Associations between these diseases have been hypothesized and studied for decades. In particular, psychosocial stressors associated with anxiety disorders raise autonomic arousal via the hypothalamic-pituitary axis which increases circulating catecholamines. This heightened arousal is associated with an increased risk of hypertension and a pro-inflammatory state and, consequently, development of coronary heart disease. This association holds across the spectrum of anxiety disorders (generalized anxiety, posttraumatic stress disorder, panic disorder, and obsessive compulsive disorder) and also when controlling for comorbid conditions such as depression and physical ailments. Multiple cross sectional studies reveal a positive association between anxiety and hypertension. These associations are bidirectional, with those with hypertension being more likely to have anxiety and those with anxiety being more likely to have hypertension. However, a few studies have shown no association. Longitudinal studies point to an increased risk of development of hypertension in patients who suffer from anxiety. More convincing studies show links between anxiety symptoms and disorders, including panic disorder and PTSD, and cardiovascular outcomes. Drawing broad conclusions from these studies is challenging, however, given the multiplicity of scales used to measure anxiety disorders. Anxiety, hypertension, and CHD are common conditions seen in primary care, and anxiety may be an important predictor of future CHD outcomes. Better recognition of the association of these conditions and the possible roles of each in development of the other should alert primary care providers to be vigilant in monitoring and treating anxiety, hypertension, and CHD.

Association of polychlorinated biphenyls with hypertension in the 1999–2002 National Health and Nutrition Examination Survey

The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.

Psychosocial Factors and Progression From Prehypertension to Hypertension or Coronary Heart Disease

PURPOSE This study explored the influence of trait anger and long-term psychological stress on progression to hypertension and incident coronary heart disease (CHD) in persons with prehypertension. METHODS A secondary data analysis was performed using the Atherosclerosis Risk in Communities (ARIC) study, a cohort of men and women aged 45 to 64 years at enrollment. Participants with blood pressures in the prehypertension range at the second visit conducted between 1990 and 1992, free of heart disease or stroke, and observed through the end of the ARIC study (1996–1998) were included (N = 2,334). The main outcomes were progression from prehypertension to hypertension and prehypertension to CHD or CHD death. RESULTS After adjusting for various covariates, high levels of trait anger, compared with low/moderate levels (odds ratio [OR] 1.53; 95% confidence interval [CI], 1.05–2.24), were associated with progression from prehypertension to hypertension. After stratifying on sex, trait anger was predictive for men only (OR 1.71; 95% CI 1.04–2.83). In survival analysis, trait anger was associated with progression to CHD for men (hazard ratio [HR] 1.92; 95% CI, 1.07–3.54). Long-term psychological stress was also associated with risk of incident CHD (HR 1.68; 95% CI 1.18–2.40). CONCLUSIONS High levels of trait anger in middle-aged prehypertensive men were associated with increased risk of progressing to hypertension and incident CHD. Long-term stress was also associated with increased risk of incident CHD in both men and women.

Leukocyte telomere length and coronary artery calcification.

OBJECTIVE Leukocyte telomere length is representative of biological aging and is associated with clinical coronary artery disease but its association with coronary atherosclerosis is unclear. The objective of this study was to examine the association of telomere length with coronary artery calcification in middle aged adults. METHODS Leukocyte telomere length was measured with a quantitative PCR-based technique and coronary artery calcification (CAC) scoring was performed on a dual-source CT scanner in a sample of 325 adults aged 40-64 years old free of previously diagnosed diabetes, CHD, stroke and cancer. We used logistic regression to determine the association of presence of CAC (Agatston score >0 versus 0) with telomere length adjusted for age, gender, race and metabolic syndrome. Finally, we examined the relation of telomere length to extensiveness of CAC. RESULTS The unadjusted odds ratio of having CAC for the shortest tertile of telomere length versus the longest was 3.39 (95% CI 1.85-6.20). After adjustment for age, race, gender and metabolic syndrome the odds decreased but remained significant (OR 2.36; 95% CI 1.23-4.52). Mean telomere length was significantly shorter with more extensive coronary calcification. The correlation between telomere length and chronological age was r=-0.19 (p<.001) while the correlation between telomere length and arterial age was r=-0.22 (p<.001). CONCLUSIONS In conclusion, telomere length is negatively associated with the presence of coronary atherosclerosis in a low risk cohort free of previously diagnosed CVD.

Association of urinary polycyclic aromatic hydrocarbons and serum C-reactive protein.

The association of 9 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) with serum C-reactive protein (CRP) was investigated using the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The unweighted number of participants included was 999, which represented 139,362,776 persons in the non-institutionalized US population. In adjusted logistic regressions, two OH-PAHs, 2-hydroxyphenanthrene and 9-hydroxyfluorene, were associated with elevated CRP (>3mg/l). Logistic regressions were adjusted for age, gender, race, exercise, body mass index, smoking status, diabetes, and hypertension. 2-Hydroxyphenanthrene >148ng/g creatinine had an odds ratio of 3.17 (95% CI 1.73-5.81) compared to 2-hydroxyphenanthrene < or =48ng/g creatinine, and 9-hydroxyfluorene >749ng/g creatinine had an odds ratio of 2.28 (95% CI 1.08-4.83) compared to 9-hydroxyfluorene < or =160ng/g creatinine. Intermediate levels of 2-hydroxyphenanthrene (49-148ng/g creatinine), and 9-hydroxyfluorene (161-749ng/g creatinine) were also significantly associated with elevated CRP compared to the respective reference categories. In a combined analysis, OH-PAHs were classified as low, medium, and high. Low OH-PAH was 2-hydroxyphenanthrene < or =48ng/g creatinine and 9-hydroxyfluorene < or =160ng/g creatinine. High OH-PAH was 2-hydroxyphenanthrene >148ng/g creatinine or 9-hydroxyfluorene >749ng/g creatinine. Participants not assigned to the low or high categories were classified as having medium OH-PAH concentrations. Compared to the low OH-PAH group, high OH-PAH had an odds ratio of 3.60 (95% CI 2.01-6.46) in an adjusted logistic regression. Given that inflammation (characterized here by CRP) is an important factor in the development of atherosclerosis and cardiovascular disease, these results suggest a role for OH-PAHs in the progression of atherosclerosis.

Telomere length and adiposity in a racially diverse sample.

Objective:To evaluate the cross-sectional relationship of anthropometric measures (body mass index (BMI) and visceral fat and the adipokines leptin and adiponectin) with telomere length in a racially diverse sample.Design:Cross-sectional study of participants recruited from a health science university.Subjects:Participants include 317 men and women aged 40–64 years without diagnosed diabetes, cardiovascular disease (defined as coronary heart disease or stroke/transient ischemic attack) or cancer.Results:Study participants were 54.9% female, 58% non-Hispanic white (NHW) and 42% non-Hispanic Black (NHB). Of the sample, 76% were either overweight or obese. Linear regressions showed no association between the anthropometric measures (BMI (kg m−2), visceral fat (cm2), adiponectin (μg ml−1), leptin (ng ml−1) or adiponectin to leptin ratio (μg ng−1)) assessed in a continuous manner and telomere length assay ratio, either for the whole sample or when stratified by race or by gender.Conclusion:This study finds no linear associations between telomere length and several measures of obesity in a sample of NHB and NHW men and women. Further studies are needed to identify factors that influence telomere length in diverse populations.

Prehypertension and Insulin Resistance in a Nationally Representative Adult Population

Prehypertension is associated with increased risk of cardiovascular disease and progression to hypertension. Insulin resistance (IR) is also related to cardiovascular risk. It is unknown whether individuals with prehypertension also have higher IR. The purpose of this study was to examine the association between prehypertension and IR. The National Health and Nutrition Examination Survey 1999–2002 was used to determine odds of IR by fasting insulin level >12.2 μU/mL or homeostasis model assessment (HOMA) ≥2.6 among nondiabetic adults aged 20 to 80 years across blood pressure categories. Compared with normotensives, odds of IR were over 60% higher for prehypertensive individuals by both IR measures: fasting insulin (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.12–2.48) and HOMA (OR, 1.67; 95% CI, 1.22–2.30). After stratifying by sex, IR was associated with prehypertension in only men for both IR measures. In conclusion, prehypertension is associated with higher IR in men, which may confer additional cardiovascular disease risk.

Impact of EHR-based clinical decision support on adherence to guidelines for patients on NSAIDs: a randomized controlled trial.

PURPOSE Electronic health records (EHRs) with clinical decision support hold promise for improving quality of care, but their impact on management of chronic conditions has been mixed. This study examined the impact of EHR-based clinical decision support on adherence to guidelines for reducing gastrointestinal complications in primary care patients on nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS This randomized controlled trial was conducted in a national network of primary care offices using an EHR and focused on patients taking traditional NSAIDs who had factors associated with a high risk for gastrointestinal complications (a history of peptic ulcer disease; concomitant use of anticoagulants, anti-platelet medications [including aspirin], or corticosteroids; or an age of 75 years or older). The offices were randomized to receive EHR-based guidelines and alerts for high-risk patients on NSAIDs, or usual care. The primary outcome was the proportion of patients who received guideline-concordant care during the 1-year study period (June 2007–June 2008), defined as having their traditional NSAID discontinued (including a switch to a lower-risk medication), having a gas-troprotective medication coprescribed, or both. RESULTS Participants included 27 offices with 119 clinicians and 5,234 high-risk patients. Intervention patients were more likely than usual care patients to receive guideline-concordant care (25.4% vs 22.4%, adjusted odds ratio = 1.19; 95% confidence interval, 1.01–1.42). For individual high-risk groups, patients on low-dose aspirin were more likely to receive guideline-concordant care with the intervention vs usual care (25.0% vs 20.8%, adjusted odds ratio = 1.30; 95% confidence interval, 1.04–1.62), but there was no significant difference for patients in other high-risk groups. CONCLUSIONS This study showed only a small impact of EHR-based clinical decision support for high-risk patients on NSAIDs in primary care offices. These results add to the growing literature about the complexity of EHR-based clinical decision support for improving quality of care.

Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

Objective: To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. Methods: We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45–84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). Results: A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80–1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. Conclusions: These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

Antihypertensive prescribing practices: impact of the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

This national study examines the impact of the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on the prescribing of thiazide‐type diuretics and other antihypertensive medications for patients with newly diagnosed hypertension. A cross‐sectional analysis was conducted using data from a national network of electronic health records for 2 groups with newly diagnosed hypertension and started on antihypertensive medications: one a year before and the other a year after the publication of ALLHAT. The percentage of new hypertensives started on thiazides increased from 29% pre‐ALLHAT to 39% post‐ALLHAT. An increase was also seen for angiotensin receptor blockers, while prescribing for angiotensin‐converting enzyme inhibitors, calcium channel blockers, and β‐blockers declined. There was no significant change in prescriptions for α‐blockers. Prescriptions for thiazides for patients with newly diagnosed hypertension increased after the publication of ALLHAT. Data from large national trials can have a considerable impact on prescribing practices.