Large meta-analysis links anger, hostility with CHD risk, particularly in men

Moral of the story: Take 10 deep breaths before you get angry, your heart will thank you later.

Heartwire - Prevention

Large meta-analysis links anger, hostility with CHD risk, particularly in men

March 10, 2009 | Deborah Wormser

London, UK - Anger and hostility were associated with a 19% increase in coronary heart disease (CHD) events in healthy individuals and a 24% increase in risk among those with preexisting CHD, researchers report in the first large, systematic meta-analysis to show significant links between those two mind states and CHD [1].

"The harmful effect of anger and hostility has been widely asserted, but previous reviews have been inconclusive," Dr Yoichi Chida and Dr Andrew Steptoe (both from University College London, UK) write in their review published in the March 17, 2009 issue of the Journal of the American College of Cardiology.

"Intriguingly, the harmful effect of anger and hostility on CHD events in the healthy populations was greater in men than women," the researchers write. In the healthy-population studies, the researchers found a strong association between anger and hostility and CHD in men (HR 1.22, p<0.001),>

"Previous meta-analyses failed to show significant associations of anger and hostility with CHD," Chida told heartwire. Chida added that this report includes several studies published since the last major meta-analytical review.

Chida's review included 21 articles (71 606 individuals) on CHD outcomes in healthy populations and 18 articles (n=8120) of people with preexisting CHD, from studies conducted in Australasia, Europe, and America. Anger and hostility were associated with increased CHD events in the healthy-population studies, with a combined HR of 1.19 (p=0.008), and those emotions were associated with poor prognosis in the population with existing CHD (HR 1.24, p=0.002). In the studies of individuals with baseline CHD, the poor prognosis associated with anger and hostility persisted after researchers fully controlled for basal disease status and treatment, the article states.

Although the body of research investigating the association between anger and hostility and CHD has grown during the past 25 years, several reviews of the literature have produced different findings, possibly because some looked at individual facets of the overall construct, such as hostility alone. Another possible confounder could be the inclusion of cross-sectional, retrospective, and prospective studies in previous reviews, the researchers write in their analysis, which was limited to prospective cohort investigations.

The analysis found that CHD risk appeared to be mediated through high-risk behaviors, with the association between anger/hostility and CHD becoming no longer significant after full adjustment for behavioral factors such as smoking, physical activity, body-mass index, or socioeconomic status.

Small but notable risk

In an accompanying editorial [2], Dr Johan Denollet and Dr Susanne S Pedersen (both from Tilburg University, the Netherlands) point out that while the overall size of the associations between anger and hostility and subsequent CHD reported by Chida et al might seem small, it appears notable when compared with the 11% increased risk associated with von Willebrand factor in the Reykjavik Study [3].

"This meta-analytic review is of high scientific quality and provides us with a reliable estimate of the risk associated with anger/hostility," Denollet told heartwire. "This review has important clinical implications, because it supports the notion that adverse psychological factors do matter in the development and progression of CHD. Moreover, these findings indicate that psychological factors, in this case anger/hostility, start to show their adverse effect after a couple of years, suggesting that these factors are especially of importance in the long run and that more long-term follow-up studies are needed."

Symptoms of anger/hostility should be taken seriously. "Clinicians may consider referring their coronary patients with high levels of anger for behavioral intervention," he said in the interview with heartwire.

Regarding the findings that the association between anger/hostility and CHD appears mediated by lifestyle behaviors and socioeconomic status, Denollet told heartwire, "I think that a number of these unhealthy lifestyles—smoking, overeating—may reflect attempts to downregulate feelings of tension associated with anger/hostility. Socioeconomic status may reflect a vulnerability factor for increased levels of anger/hostility."

One important direction for future research would be the role of emotion-regulation strategies that might moderate the effects of anger and hostility.

"There is some evidence that suppression of anger increases the risk of hypertension and coronary disease and that inhibition of emotion and behavior in general may further increase the risk of stress-related CHD. Future research should more often focus on the interplay between negative emotions and emotion-regulation strategies as a determinant of major coronary events," Denollet said.

"I think we need to be careful to not simply conclude that 'anger is bad for the heart.' After all, anger is a natural emotion that can be very adaptive (eg, as a warning signal), provided that this negative emotion is regulated and used in a socially meaningful and adaptive way," he added.

Chida receives support from the Kanae Foundation for the Promotion of Medical Science and the Medical Research Council. Steptoe receives support from the British Heart Foundation. Denollet and Pedersen report no disclosures.

Sources

1. Chida Y, Steptoe A. The association of anger and hostility with future Coronary Heart Disease. J Am Coll Cardiol 2009; 53:936-946. DOI:10.1016/j.jacc.2008.11.044.
2. Denollet J, Pedersen SS. Anger, depression, and anxiety in cardiac patients. J Am Coll Cardiol 2009; 53:947-9.
3. Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New Engl J Med 2004; 350:1387-97.

Very low LDL and normal BP result in slowest progression of atherosclerosis

Moral of the story: 2 thing - Blood Pressure, LDL. Worry about those two things. Get them back to normal and you will go a long way towards preventing heart disease.

Heartwire - Clinical cardiology

Very low LDL and normal BP result in slowest progression of atherosclerosis

March 23, 2009 | Michael O'Riordan

Cleveland, OH - Patients with coronary artery disease (CAD) who reduce LDL cholesterol to very low levels and achieve a normal systolic blood pressure have the slowest progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS), a new study has shown [1]. The findings, according to investigators, support the need for intensive management of global risk in patients with CAD.

"What's happened in recent years with the advent of more potent statins and all the education done around that is that getting people to LDL goal is achieved fairly well," senior investigator Dr Steven Nissen (Cleveland Clinic, OH) told heartwire. "But getting people to dual goals is not done well around the country. We wanted to tell people that there really is some pretty good evidence here that if you get your blood pressure down to normal and your LDL down below 70, this is a disease that can not only be halted, but potentially can even regress."

The results of the study are published in the March 24, 2009 issue of the Journal of the American College of Cardiology.

Seven studies rolled into one

To clarify the relationship between LDL cholesterol and systolic blood pressure and their effects on coronary plaque progression, the researchers, led by Dr Adnan Chhatriwalla (Cleveland Clinic) studied 3437 patients with established CAD enrolled in seven clinical trials. The studies included REVERSAL, CAMELOT, ACTIVATE, ASTEROID, ILLUSTRATE, PERISCOPE, and STRADIVARIUS, a group of trials that investigated statins, acyl coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester transfer protein (CETP) inhibitors, rimonabant, ACE inhibitors, and calcium-channel blockers, among others.

Patients were stratified into four groups based on their average on-treatment LDL-cholesterol levels and systolic blood pressure:

• LDL cholesterol <70 mg/dL and systolic blood pressure <120 mm Hg.
• LDL cholesterol <70 mg/dL and systolic blood pressure >120 mm Hg.
• LDL cholesterol >70 mg/dL and systolic blood pressure <120 mm Hg.
• LDL cholesterol >70 mg/dL and systolic blood pressure >120 mmHg.

Changes in atheroma burden were monitored by IVUS, which was measured at baseline and at 18 to 24 months.

Patients with very low LDL-cholesterol levels and normal systolic blood pressure, group 1, had the least progression in percent atheroma volume (PAV) and total atheroma volume (TAV). In addition, these patients also had less frequent atheroma progression and more frequent regression. In patients with systolic blood pressure >120 mm Hg who still had very low LDL cholesterol levels, group 2, less progression of PAV and TAV was also observed.

"It really makes a big difference if you can get both down," said Nissen. "It's a big payoff for patients if physicians are diligent about getting LDL and blood pressure under control."

Among patients with LDL-cholesterol levels >70 mg/dL, normal systolic blood pressure was associated with no greater reduction in PAV or TAV, suggesting that lipid lowering has a larger impact than blood-pressure control on plaque progression, findings supported by recent clinical trials.

The findings challenge current treatment recommendations for hypertension, noted Nissen, and he recommends treating prehypertensive patients with coronary disease, those with pressures of 120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic. In the CAMELOT study, he points out, the calcium-channel blocker amlodipine decreased the risk of cardiovascular events in patients with CAD and normal blood pressure, as did the ACE inhibitor enalapril, but to a lesser extent.

"Remember that these are all people who have coronary artery disease," said Nissen. "These are not your typical primary-prevention patients with hypertension. They already have atherosclerotic disease in their coronaries. We think the evidence is pretty strong that if you already have plaques in your coronaries, you really to have a lower blood-pressure target. . . . Our IVUS data suggest that there is opportunity here to help patients."

Nissen admitted that the issue needs to be studied further and that the ongoing AQUARIUS study will assess changes in atherosclerotic disease progression with aliskiren (Tekturna, Novartis) when given in addition to standard therapy in CAD patients with prehypertension.

More data still needed

In an editorial accompanying the published study, Drs Jonathan Tobis and Alice Perlowski (University of California, Los Angeles) write that human and animal data make clear that a combination of aggressive lipid and blood-pressure control are necessary for a maximum attenuation of plaque progression, improved endothelial function, and reduced inflammation caused by oxidative stress [2].

Regarding the treatment of prehypertensive patients, Tobis and Perlowski write that a lack of data has contributed to a delayed acceptance of the need for drug therapy. In addition to AQUARIUS, the ongoing SPRINT, which is comparing intensive blood-pressure control (<120>130 mm Hg who have one additional risk factor, will help answer those questions.

The editorialists note that plaque progression/regression on IVUS is helpful in determining whether or not clinicians are helping their patients, but hard clinical end points are still needed, especially as they are shown to correspond with predictions based on the IVUS surrogates. Until then, "conclusions derived from these trials should be considered inferential, to be used as guides for future trials focused on clinical-outcomes measures," they write.

Asked about the polypill, Nissen told heartwire that he was not an initial fan, but with these and other data, he is starting to warm up to it. "The idea of having something that you go and get for $10 for three months that would control your blood pressure and your lipids, this study makes the case that it might make some sense."

New results about a polypill approach for primary prevention, combining a BP-lowering drug, a statin, and aspirin in a single pill, will be presented at the American College of Cardiology 2009 meeting next week.

Nissen reports receiving research support from AstraZeneca, Eli Lilly, Pfizer, Takeda, Sankyo, and Sanofi-Aventis and that he donates honoraria, consulting fees, and other payments directly to charity. Chhattriwalla reports no conflicts.

Sources

1. Chhatriwalla AK, Nicholls SJ, Wang TH, et al. Low levels of low-density lipoprotein cholesterol and blood pressure and progression of coronary atherosclerosis. J Am Coll Cardiol 2009; 53: 1110-1115.
2. Tobis JM, Perlowski A. Atheroma volume by intravascular ultrasound as a surrogate for clinical endpoints. J Am Coll Cardiol 2009; 53: 1116-1118.

Short Sleep Duration and Incident Coronary Artery Calcification

Moral of the story: We have all heard that sleep is good for you, and this is yet another reason that statement is extremely true. Sleeping more will decrease your risk for developing atherosclerosis, plaque development and hardening of the arteries (AHA explanation).

Short Sleep Duration and Incident Coronary Artery Calcification

Christopher Ryan King, BS; Kristen L. Knutson, PhD; Paul J. Rathouz, PhD; Steve Sidney, MD, MPH; Kiang Liu, PhD; Diane S. Lauderdale, PhD

JAMA. 2008;300(24):2859-2866.(http://jama.ama-assn.org/cgi/content/abstract/300/24/2859)

Context Coronary artery calcification is a subclinical predictor of coronary heart disease. Recent studies have found that sleep duration is correlated with established risk factors for calcification including glucose regulation, blood pressure, sex, age, education, and body mass index.

Objective To determine whether objective and subjective measures of sleep duration and quality are associated with incidence of calcification over 5 years and whether calcification risk factors mediate the association.

Design, Setting, and Participants Observational cohort of home monitoring in a healthy middle-aged population of 495 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort Chicago site (black and white men and women aged 35-47 years at year 15 of the study in 2000-2001 with follow-up data at year 20 in 2005-2006). Potential confounders (age, sex, race, education, apnea risk, smoking status) and mediators (lipids, blood pressure, body mass index, diabetes, inflammatory markers, alcohol consumption, depression, hostility, self-reported medical conditions) were measured at both baseline and follow-up. Sleep metrics (wrist actigraphy measured duration and fragmentation, daytime sleepiness, overall quality, self-reported duration) were examined for association with incident calcification. Participants had no detectable calcification at baseline.

Main Outcome Measure Coronary artery calcification was measured by computed tomography in 2000-2001 and 2005-2006 and incidence of new calcification over that time was the primary outcome.

Results Five-year calcification incidence was 12.3% (n = 61). Longer measured sleep duration was significantly associated with reduced calcification incidence (adjusted odds ratio, 0.67 per hour [95% confidence interval, 0.49-0.91 per hour]; P = .01). No potential mediators appreciably altered the magnitude or significance of sleep (adjusted odds ratio estimates ranged from 0.64 to 0.68 per sleep hour; maximum P = .02). Alternative sleep metrics were not significantly associated with calcification.

Conclusion Longer measured sleep is associated with lower calcification incidence independent of examined potential mediators and confounders.

Author Affiliations: Department of Health Studies, University of Chicago, Chicago, Illinois (Mr King and Drs Knutson, Rathouz, and Lauderdale); Division of Research, Kaiser Permanente, Oakland, California (Dr Sidney); and Department of Preventive Medicine, Northwestern University, Chicago, Illinois (Dr Liu).