Women face more risk factors, suffer different symptoms, and get less research and treatment; could some blame belong to calcium? 06/06/2017
Cardiologist Bernadine Healy, M.D., was the first female director of the National Institutes of Health.
In 1991, she penned an editorial in the New England Journal of Medicine, addressing what she called the “Yentl syndrome”.
Yentl, the Isaac B. Singer story character portrayed on film by Barbra Streisand, disguises as a man to attend a religious school (yeshiva) barred to women.
As Dr. Healy wrote, “… women have all too often been treated less than equally in social relations, political endeavors, business, education, research, and in health care.”
Until recently, men made up most subjects in studies concerning heart disease and many other conditions.
Fortunately, that’s begun to change, accompanied by greater efforts to publicize heart-health differences between the sexes, like the Go Red for Women campaign.
But many women remain unaware of the differences between their typical symptoms of heart disease and attacks and men's.
Gender distinctions in heart symptoms
Cardiovascular disease (CVD) kills one out of three men and women alike.
Despite comparable risk rates, women get less aggressive treatment, and fewer get included in clinical trials.
Even after accounting for age, the available evidence reveals several disturbing disparities between the genders:
- Women are more likely to die within the first few weeks after suffering a heart attack.
- Survival rates within a year of a first heart attack are lower in women than in men: 38% of women will die, versus 25% of men
- Compared with men of the same age, women who suffer a heart attack under age 50 are twice as likely to die from it.
These are some of the likely explanations for these disparities:
- Women are more likely to have other debilitating conditions associated with heart disease.
- Women are less physically and mentally healthy prior to a heart attack, compared with male victims of the same age.
- After heart attack, women are less likely than men to receive therapies known to improve survival, such as beta blockers, ACE inhibitors, and aspirin. This disparity promotes a higher rate of complications after heart attacks in women.
Women also wait longer to go to an emergency room when having a heart attack, and physicians are slower to recognize the problem for two reasons:
- Women's typical patterns of chest pain are less obviously signs of a heart attack.
- Women are less likely to show changes on EKG tests that clearly signal a heart attack.
While the major risk factors for CVD are similar for men and women, women have higher rates of most risk factors.
And women face gender-specific risk factors, such as pregnancy-related health conditions and the hormonal disruptions related to the transition to menopause.
Gender differences, by the numbers
These are some of the gender related heart-disease disparities:
- Women represent only 38% of the participants in clinical trials.
- Women 45 and younger are more likely than men to die within a year of their first heart attack.
- Men are two to three times more likely to receive an implantable defibrillator for the prevention of sudden cardiac death.
- Within five years of a first heart attack, 47% of women will die, develop heart failure, or suffer from a stroke, compared with only 36% of men
- Only one-quarter of cardiovascular clinical trials report sex-specific results, making it difficult for doctors to draw conclusions about their implications for women.
Sadly, doctors are more likely to discuss heart disease prevention with men, and women’s symptoms are often attributed to other conditions, including stress, panic attacks or even hypochondria.
Sex-specific symptoms of heart trouble
Women are routinely misdiagnosed when they report symptoms of heart disease or a heart attack.
According to the American Heart Association (AHA), women experience symptoms distinct from men’s before and during a heart attack.
About 95% of women notice that something wasn’t right in the weeks before their heart attacks.
These are the symptoms women typically experience in the weeks before a heart attack, followed by the proportion who report them:
One month prior to heart attack
- Unusual fatigue – 71%
- Sleep disturbance – 48%
- Shortness of breath – 42%
- Indigestion – 39%
- Anxiety – 36%
- Racing heart – 27%
And these are women’s typical heart attack symptoms, in rough order of frequency:
During a heart attack
- Chest discomfort
- Shortness of breath
- Weakness, difficulty moving
- Unusual fatigue during/after activities
- Cold sweat, nausea, dizziness, or lightheadedness
- Weak or heavy-feeling arms
- Pain in one or both arms, the back, neck, jaw, or stomach
Like men, women’s most common heart attack symptom is chest discomfort.
However, recent evidence suggest that chest pain is much less common in women than in men.
We know that, compared with most men, most women experience diffuse chest discomfort — pressure, squeezing, or fullness — and perhaps don't perceive or report them as "pain".
“Chest pain” is a bit misleading, because it covers a range of symptoms from uncomfortable pressure, squeezing, fullness or pain, anywhere in the chest. The signs may last more than a few minutes, and disappear and return.
The Cleveland Clinic also cites these women-specific symptoms:
- Sudden pain that awakens you from sleep.
- Sudden pain unrelated to physical exertion.
- Pain specific to the left, lower side of the jaw.
- Pain in either arm — not just the left, like many men.
- Pain in the lower or upper back that starts in the chest.
More risk factors = greater risks
The American Heart Association says that women over 65 are more likely than men to have one or more risk factors in the years leading up to developing cardiovascular disease.
These are the proportions of women who suffer from underlying health conditions, compared with for men:
- Diabetes – 40% vs. 27%
- Obesity – 55% vs. 48%
- Heart failure – 6% vs. 2%
- History of stroke – 6% vs. 3%
- Renal (kidney) failure – 13% vs. 9%
And women experience gender-specific risk factors that put them at additional risk:
- Higher blood pressure during menopause
- Higher testosterone levels before menopause
- Autoimmune diseases, which afflict more women
- Depression, anxiety, and/or stress, which afflict more women
The underlying difference between genders
Cardiovascular disease (CVD) takes different forms in women and men.
In fact, C. Noel Bairey Merz, M.D. — director of the Women’s Heart Center at the Cedars-Sinai Heart Institute — believes that CVD in women and men should be given different names.
As she says, “The more we find out, the more it becomes clear that men and women can experience different [cardiovascular] diseases and the medical names for those diseases should reflect the differences.”
Cardiovascular disease is characterized by “ischemia”, which simply means constricted blood flow, in this case to the heart.
Over time, lack of blood flow weakens heart muscles and causes irregular heart rhythms, both of which contribute to heart attacks and rhythm-related sudden cardiac death.
Women with CVD suffer from restricted blood flow (ischemia) through smaller coronary blood vessels.
Men with CVD typically accumulate clumps of plaque in major coronary arteries, but women’s plaque distributes evenly throughout artery walls.
This difference results in women’s angiographic studies being misinterpreted as “normal”.
Both blood-constriction problems fall under the umbrella of “ischemic heart disease”, but Dr. Bairey Merz believes that label should apply only to CVD in women.
In contrast, she says, cardiovascular disease in men should be called “coronary artery disease”.
Because women often don’t show significant plaque build-up in their coronary arteries, their form of cardiovascular disease is harder to diagnose with conventional cardiac tests.
Could the gender difference be partially explained by calcium?
Excess calcium in the blood can promote development of arterial plaque.
And differences in the activity or "expression" levels of genes in men and women may explain differences in plaque buildup.
Earlier this year, an Israeli research team identified some 6,500 genes that are expressed differently in men and women, meaning that they’re more active in one or the other gender.
These included genes that express only in the left ventricles (pumping chambers) of women’s hearts — one of which is related to calcium uptake.
That gene showed very high expression (activity) levels in younger women, but it becomes much less active after menopause.
So, this gene may help prevent plaque buildup in younger women by reducing the amount of calcium in the blood, while boosting the amounts in bones.
And they suspect that expression of this calcium-uptake gene fades or end after menopause, leading to higher risk for both heart disease and osteoporosis.
As Dr. Bairey Merz says, “We are just at the beginning of understanding the differences between the sexes when it comes to heart disease.”
- American Heart Association. Heart Attack Risk Factors: Women vs. Men - Go Red For Women. Go Red For Women, 16 Sept. 2013. Accessed at https://www.goredforwomen.org/about-heart-disease/heart_disease_research-subcategory/heart-attack-risk-factors-women-vs-men/
- American Heart Association. Heart Attack Symptoms in Women. Accessed at http://www.heart.org/HEARTORG/Conditions/HeartAttack/WarningSignsofaHeartAttack/Heart-Attack-Symptoms-in-Women_UCM_436448_Article.jsp#.WTrV92grLIV
- Appelman Y, van Rijn BB, Ten Haaf ME, Boersma E, Peters SA. Sex differences in cardiovascular risk factors and disease prevention. Atherosclerosis. 2015 Jul;241(1):211-8. doi: 10.1016/j.atherosclerosis.2015.01.027. Epub 2015 Jan 28. Review
- Barouch L. Heart Disease: Differences in Men and Women. Johns Hopkins Medicine. The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System, 15 Apr. 2016. Web. 10 Mar. 2017.
- Bucholz EM, Butala NM, Rathore SS, Dreyer RP, Lansky AJ, Krumholz HM. Sex differences in long-term mortality after myocardial infarction: a systematic review. Circulation. 2014 Aug 26;130(9):757-67. doi: 10.1161/CIRCULATIONAHA.114.009480. Epub 2014 Jul 22. Review.
- Cho L, M.D. Women: Don’t Ignore These 3 Subtle Heart Attack Symptoms. The Cleveland Clinic. March 3, 2016. Accessed at https://health.clevelandclinic.org/2016/03/women-dont-ignore-3-subtle-heart-attack-symptoms/
- Claassen M, Sybrandy KC, Appelman YE, Asselbergs FW. Gender gap in acute coronary heart disease: Myth or reality? World J Cardiol. 2012 Feb 26;4(2):36-47. doi: 10.4330/wjc.v4.i2.36.
- Gijsberts CM, Agostoni P, Hoefer IE, Asselbergs FW, Pasterkamp G, Nathoe H, Appelman YE, de Kleijn DP, den Ruijter HM. Gender differences in health-related quality of life in patients undergoing coronary angiography. Open Heart. 2015 Aug 27;2(1):e000231. doi: 10.1136/openhrt-2014-000231. eCollection 2015.
- Healy B. The Yentl syndrome. N Engl J Med. 1991 Jul 25;325(4):274-6.
- Maas AH, Appelman YE. Gender differences in coronary heart disease. Neth Heart J. 2010 Dec;18(12):598-602
- Maas AH, van der Schouw YT, Regitz-Zagrosek V, Swahn E, Appelman YE, Pasterkamp G, Ten Cate H, Nilsson PM, Huisman MV, Stam HC, Eizema K, Stramba-Badiale M. Red alert for women's heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010. Eur Heart J. 2011 Jun;32(11):1362-8. doi: 10.1093/eurheartj/ehr048. Epub 2011 Mar 15. Review.
- McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin BJ. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003 Nov 25;108(21):2619-23. PubMed PMID: 14597589.
- Mosca L, Barrett-Connor E, Wenger NK. Sex/gender differences in cardiovascular disease prevention: what a difference a decade makes. Circulation. 2011 Nov 8;124(19):2145-54. doi: 10.1161/CIRCULATIONAHA.110.968792.
- Ten Haaf ME, Rijndertse M, Cheng JM, de Boer SP, Garcia Garcia HM, van Geuns RM, Regar E, Lenzen MJ, Appelman Y, Boersma E. Sex differences in plaque characteristics by intravascular imaging in patients with coronary artery disease. EuroIntervention. 2016 Nov 22. pii: EIJ-D-16-00361. doi: 10.4244/EIJ-D-16-00361. [Epub ahead of print]
- von Haehling S. Recent developments in the treatment of heart failure: highlights from the American Heart Association’s Scientific Sessions, Los Angeles, California, 3 - 7 December 2012. Expert Opin Investig Drugs. 2013 Jul;22(7):933-7. doi: 10.1517/13543784.2013.798301. PubMed PMID: 23656525.
- When It Comes to Heart Disease, Women and Men Are Not Equal. Cedars-Sinai. Accessed at https://www.cedars-sinai.edu/About-Us/HH-Landing-Pages/When-it-comes-to-heart-disease-women-and-men-are-not-equal.aspx
- Weizmann Institute of Science. Researchers Identify 6,500 Genes That Are Expressed Differently in Men and Women. March 5, 2017. Accessed at http://wis-wander.weizmann.ac.il/life-sciences/researchers-identify-6500-genes-are-expressed-differently-men-and-women
- Women's Heart Foundation, Inc. Women and heart disease facts. Accessed at http://www.womensheart.org/content/heartdisease/heart_disease_facts.asp