Electronic Journal Club 2008

This journal club is a part of the education component of Women's Heart Health at Stanford and serves to keep all of us informed and up to date on sex differences in cardiovascular disease.

The key feature of the articles is that they will address sex differences related to cardiovascular disease, but they can come from any discipline (ie, mental health, genetics, ob/gyn, heart failure, nutrition, etc.) Sex-specific articles will also be considered.

JANUARY 2008: Article and the analysis
Impact of Impaired Fasting Glucose on Cardiovascular Disease
Levitsky et al. J Am Coll Cardiol 2008;51:264-70.

This month's article joins a growing body of literature suggesting that elevated fasting glucose levels and the presence of diabetes confer a greater relative risk of CHD in women than in men. This article focuses on impaired fasting glucose values from 100mg/dl to 125mg/dl, demonstrating that IFG is predictive of CHD in women, but not in men, and that women with an IFG of 110 to 125 have nearly the same risk of CHD as women who already have diabetes. It raises the questions of whether these sex differences are due to intrinsic biologic differences or differences in risk factor management, and if sex-specific cut points for IFG should exist.

As a reminder, February is American Heart Month (proclaimed such by the President since 1963) and February 1 is National Wear Red Day (part of the AHA's Go Red for Women campaign to raise awareness of heart disease in women).

FEBRUARY 2008: Article and the analysis
Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease
Berends et al. Hypertension 2008;51:1-8 (published online first in special Go Red for Women issue).

I had the pleasure of giving Ob/Gyn Grand Rounds a couple of weeks ago. This month's article was chosen not because it involves ground-breaking research, but because it highlights an important finding that may get lost in a gap between the fields of Ob/Gyn and Cardiovascular Medicine. There are several pregnancy-related disorders (such as preeclampsia and IUGR) that are associated with a future risk of cardiovascular disease. It is felt by many that this association is a result of multiple common risk factors, including insulin resistance, hypertension, abdominal obesity, and dyslipidemia, and that endothelial dysfunction may serve as a common pathogenic link.

A collaboration between Cardiovascular Medicine and Ob/Gyn may aid in the identification, screening, and treatment of these patients through aggressive primary prevention. This may, in turn, result in a reduction of both pregnancy-related disorders and future cardiovascular disease.

MARCH 2008: Article and the analysis
Prevalence of Angina in Women Versus Men: A Systematic Review and Meta-Analysis of International Variations Across 31 Countries
Hemingway et al. Circulation 2008;117:1526-1536

Several studies have suggested that MI is more common in men and angina is more common in women. This month's article substantiates the latter suspicion on a global scale. In doing so, it suggests that such a stable, robust finding across multiple countries is evidence for a biologic basis of this sex difference. We are left with (at least) two very important questions:
What is unique about women that they would differentially have angina rather than MI? Likewise, what is unique about men that they would differentially have MI rather than angina?
Given global evidence of a female excess in angina, might we serve the more prevalent population better by shifting away from randomized trials and clinical guidelines in angina that are male-focused?

APRIL 2008: Article and the analysis
Risk factors for myocardial infarction in women and men: insights from the INTERHEART study Anand et al. Eur Heart J 2008;29:932-940

This month we have another global perspective on sex differences, this time dealing with risk factors for acute MI. The article also looks at aged-based sex differences, an added dimension of importance that is often overlooked. Sex differences are not static across age, but influence men and women variably as they age.

Another important point that is reiterated by this article is that the traditional cardiac risk factors are applicable to both sexes, although they often impact them to different degrees. Novel risk factors in one sex and not the other remain elusive and likely do not exist.

MAY 2008: Article and the analysis
Changes in Insulin Resistance and Cardiovascular Risk During Adolescence
Moran et al. Circulation 2008;117:2361-2368

JUNE 2008: Article and the analysis
Gender Differences in Coronary Heart Disease and Health-Related Quality of Life: Findings from 10 States from the 2004 Behavioral Risk Factor Surveillance System
Ford et al. J Womens Health 2008;17:757-768

This month we look at quality of life--considered a "soft" endpoint in clinical trials, but presumably as important as mortality to your patients. Not surprisingly, patients with CHD report more physically and mentally unhealthy days than patients without CHD, but between the sexes, women report an even lower quality of life than men. There a multiple possible reasons for this. Women have more comorbidities, more angina, more anxiety and depression, and less social support. They may also be more surprised to have their illness or feel less confident in their treatment. A better understanding of why women report a lower quality of life may contribute to an improvement in their care and outcomes.

There was another notable article published this month on sex differences in the June 17 edition of JACC. This looked at a single center's experience with sex differences in short- and long-term mortality following PCI.

JULY 2008: Article and the analysis
Reduction in Sex-Based Mortality Differences with Implementation of New Cardiology Guidelines
Novack et al. Am J Med 2008;121:597-603

There are two seemingly discordant sayings I've seen in the cardiovascular sex differences literature. One is that we need to treat women more like women, and the other is that we need to treat women more like men. These are actually both true, but at different times. In those situations where women are unique (higher bleeding complications after cath), they need to be treated according to guidelines derived specifically for women, but in situations where women are simply being undertreated (statins post-MI), they need to be treated according to the same guidelines used for men.

This proves true in this month's article that shows a relative improvement in the diagnosis, treatment, and outcomes of women with acute coronary syndrome compared with men after the adoption of the 2000 ACC guidelines that improved our diagnostic and management strategies with the use of troponins and early invasive cath, regardless of sex. Certain caveats exist, however, that are not addressed in this article. First, we know that troponin is more apt to diagnose myocardial ischemia in both sexes, but it is likely a better biomarker in men than women (TIMI-18 data). Second, we know that an early invasive strategy is of benefit to all men, but only of benefit to high-risk women (generally defined by cardiac biomarkers). A meta-analysis confirming this was published this month. Having a different set of guidelines for low-risk woman is a situation where we need to treat a woman like a woman rather than like a man. Third, we know that existing secondary prevention guidelines are equally effective in women and men, which is why improved diagnostic methods, if followed by appropriate secondary prevention, will have a more beneficial effect on women, and reflect a situation where we need to treat a women more like a man.

I have included two other articles this month. One is an important updated review on MI and pregnancy, and the other is about the use of coronary calcium as a predictor of all-cause mortality in women and men. The latter article does not have any major conclusions based on sex, but is a nice demonstration of how sex differences can be displayed in an article.

AUGUST 2008: Article and the analysis
Impact of Gender on the Myocardial Metabolic Response to Obesity
Peterson et al. J Am Coll Cardiol Imag 2008;1:424-33

Our article this month explores the complex interplay between sex and obesity in the development of cardiovascular disease. The study suggests that obesity affects women more adversely than men, with women developing a less efficient myocardial metabolism. It doesn’t address the effect of body fat distribution, which would likely complicate matters further, but does remind us that studies focused on sex-related outcomes need to take into account the role of obesity on the outcome, and vice versa.

I have added a publication from JACC this month regarding the continued underrepresentation of women in mixed-sex NIH-sponsored cardiovascular randomized clinical trials.

SEPTEMBER 2008: Article and the analysis
Sex-specific Programming of Cardiovascular Physiology in Children
Jones et al. Eur Heart J 2008;29:2164-2170

This month's article explores sex differences in cardiovascular physiology that may be set into motion even before birth. Such findings have implications for maternal health and add to our understanding of adult cardiovascular risk in low birth weight children.

OCTOBER 2008: Article and the analysis
Gender Differences among Hardcore Smokers: An Analysis of the Tobacco Use Supplement of the Current Population Survey
Auguston et al. J Women’s Health 2008;17:1167-1173

This month we take a look at sex differences in smokers, particularly hardcore smokers. Because women have more healthcare provider visits than men, we have more opportunity to assist this group with smoking cessation. However, their history of heavy smoking, nicotine dependence, and social circumstances make them in need of additional strategies for smoking cessation than those currently used on typical female smokers. Male hardcore smokers pose a particular challenge due to less healthcare visits, as well as continued smoking even in the face of more smoking restrictions at home and in the workplace. I have included two other articles of interest.

The first article compares peripheral arterial response to mental stress in men versus women with coronary artery disease, concluding that men have a higher susceptibility to peripheral vasoconstriction in response to mental stress than women, and is a correlate to last month's article where we learned about sex differences in response to stress among children who were born small. The second article investigates sex differences in DVT with men having a higher prevalence, but women presenting with more extensive thrombosis associated with entire leg swelling.

NOVEMBER 2008: Article and the analysis
Gender Differences in Clinical Manifestations of Brugada Syndrome
Benito et al. J Am Coll Cardiol 2008;52:1567-73

This month's article elaborates on one of the striking sex differences in electrophysiology. Brugada syndrome is more common and lethal in men, and likewise, the predictors of a poor outcome are more clearly defined. On the other hand, women diagnosed with Brugada Syndrome have a lower risk of sudden cardiac death, but for the few that have the syndrome, we still lack clear markers to help categorize their risk. Because of the genetic and cellular basis of the syndrome, Brugada serves as a good example of where sex-based research should be the modus operandi, both at the clinical and basic science levels. There was another EP article that came out a few days ago on alcohol consumption and the risk of incident atrial fibrillation in women. I've included it for your reference.

December 2008: Article and the analysis
Sex Differences in Medical Care and Early Death After Acute Myocardial Infarction
Jneid et al. Circulation 2008;118:2803-2810

Using the American Heart Association's Get with the Guidelines-Coronary Artery Disease database, this month's article demonstrates that women presenting with an acute myocardial infarction are less likely to receive early aspirin treatement, early b-blocker treatment, revascularization procedures, or timely reperfusion compared with men. Even in the current era, women presenting with an ST-elevation myocardial infarction have a higher adjusted in-hospital mortality rate than men. This disparity in mortality is accounted for by women having an excess of very early deaths (within the initial 24 hours of hospitalization).

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