Sex differences in coronary artery disease: Pathological observations

doi:10.1016/j.atherosclerosis.2015.01.017

Atherosclerosis

Volume 239, Issue 1, March 2015, Pages 260-267

https://doi.org/10.1016/j.atherosclerosis.2015.01.017 Get rights and content

Highlights

•
We reviewed sex differences in coronary artery disease (CAD), with emphasis on coronary atherosclerotic disease.
•
CAD remains the most common cause of death in both men and women.
•
Most of the risk factors for CAD are similar for men and women, except smoking has a greater detrimental effect in women.
•
Young women tend to have plaque erosion while older women have plaque rupture.

Abstract

Cardiovascular disease (CVD) remains the most frequent cause of death in both men and women. Many studies on CVD have included mostly men, and the knowledge about coronary artery disease (CAD) in women has largely been extrapolated from studies primarily focused on men. The influence of various risk factors is different between men and women; untoward effects of smoking of CAD are greater in women than men. Furthermore, the effect of the menopause is important in women, with higher incidence of plaque erosion in young women versus greater incidence of plaque rupture in older women. This review focuses on differences in plaque morphology in men and women presenting with sudden coronary death and acute myocardial infarction.

Section snippets

Nonatherosclerotic coronary artery disease

Although a large prevalence of CVD in women is associated with coronary atherosclerosis, less common causes of acute coronary syndromes in women include spontaneous coronary dissections (SCAD), Takayasu's syndrome, and Takotsubo cardiomyopathy [7]. Takayasu's syndrome typically occurs in young women, which is predominantly associated with aortitis involving the aorta and its main branches, however coronary arteries may be less frequently involved; other rare causes include cocaine vasculitis

Risk factors

Most of the risk factors for coronary artery disease (CAD) are similar for men and women. These may be divided into modifiable risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, physical inactivity, obesity and diet, whereas the nonmodifiable are age, gender, and family history. However, the role of menopause is unique to women. CAD is unusual in premenopausal women, particularly in the absence of other risk factors [11]. On the other hand, the postmenopausal state as

Effect of menopause in coronary atherosclerosis

Coronary artery disease in women lags behind men by 10–15 years. This delay is believed to be caused by the protective effect of estrogen on coronary atherosclerosis and a decreased prevalence of coronary risk factors in young women [29]. We studied 51 cases of sudden coronary death and 47cases of non-coronary deaths in women and these were classified on the basis of histologic features including acute plaque rupture, healed plaque rupture, erosion, and vulnerable plaque (TCFA) [29]. An age of

Acute myocardial infarction in women

Arbustini et al., have reported the largest collection of patients dying from acute myocardial infarction (AMI) without thrombolytic therapy examined at one institution by one individual between 1985 and 1996 (Table 3) [32]. Of the 291 patients with AMI (women 107, men 184) 217 had rupture (mean age 68 ± 11 years) and 74 had erosion (mean age 70 ± 9 years). Erosions were more common in women (n = 40 [37%]) than in men (34 [18%]), while heart ruptures and scars were not significantly different

Conclusions

Cardiovascular disease remains the most common cause of death in both men and women in the world, and myocardial ischemia, stroke and peripheral vascular disease is by far the most frequent underlying mechanism. Most of the underlying systemic risk factors for coronary artery disease are similar between men and women. However, the impact of various risk factors is different between men and women, with smoking being a stronger risk in women than men, especially in younger women. Furthermore, the

Disclosures

Dr. Virmani receives research support from Abbott Vascular, BioSensors International, Biotronik, Boston Scientific, Medtronic, MicroPort Medical, OrbusNeich Medical, SINO Medical Technology, and Terumo Corporation; has speaking engagements with Merck; receives honoraria from Abbott Vascular, Boston Scientific, Lutonix, Medtronic, and Terumo Corporation; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. The other authors report no conflicts of interest relevant

Conflict of interest

None.

References (50)

L.J. Laslett et al.
The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American college of cardiology
J. Am. Coll. Cardiol.
(2012)
E. Rapsomaniki et al.
Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people
Lancet
(2014)
D.M. Lloyd-Jones et al.
Lifetime risk of developing coronary heart disease
Lancet
(1999)
J. Saw et al.
Nonatherosclerotic coronary artery disease in young women
Can. J. Cardiol.
(2014)
D.J. Lerner et al.
Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population
Am. Heart J.
(1986)
A.P. Burke et al.
Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis
Am. Heart J.
(2001)
A.P. Burke et al.
34th bethesda conference: task force #2–what is the pathologic basis for new atherosclerosis imaging techniques?
J. Am. Coll. Cardiol.
(2003)
F.D. Kolodgie et al.
Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death
Am. J. Pathol.
(2000)
R.S. Schwartz et al.
Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary death: relation to epicardial plaque histopathology
J. Am. Coll. Cardiol.
(2009)
M.C. Kramer et al.
Relationship of thrombus healing to underlying plaque morphology in sudden coronary death
J. Am. Coll. Cardiol.
(2010)

Cited by (216)

Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review
2024, Current Problems in Cardiology
Cardiovascular conditions in the spectrum of acute coronary syndromes are characterized by sex differences with regard to pathophysiology, risk factors, clinical presentation, invasive and pharmacologic treatment, and outcomes. This review delves into these differences, including specific subsets like myocardial infarction with non-obstructed coronary arteries or Spontaneous Coronary Artery Dissection, and alternative diagnoses like Takotsubo cardiomyopathy or myocarditis. Moreover, practical considerations are enclosed, on how a sex-specific approach should be integrated in clinical practice: in fact, personal history should focus on female-specific risk factors, and hormonal status and hormonal therapy should be assessed. Moreover, physical and psychological stressors should be investigated, particularly in the event of Spontaneous Coronary Artery Dissection or Takotsubo cardiomyopathy.
Sex differences in coronary atherosclerosis during the pre- and postmenopausal period: The Tampere Sudden Death Study
2024, Atherosclerosis
Women are believed to be protected from coronary heart disease (CHD) by the effects of estrogen but detailed studies on the vessel wall level are missing. We aimed to measure sex differences in atherosclerosis during the premenopausal and postmenopausal periods directly at the coronary arteries.
We analyzed statistics for sex differences in CHD mortality in Finland in 2020. Coronary atherosclerosis was measured using computer-assisted morphometry in 10-year age groups of 185 white Caucasian women and 515 men from the Tampere Sudden Death Study.
CHD mortality was rare in both women and men before 50 years of age. After 50 years of age, male mortality increased rapidly, with women reaching equal levels in the oldest age groups. In the autopsy series, there were no differences in fatty streak, fibrotic or calcified plaque areas, nor in the plaque area or stenosis percentage in coronary arteries between premenopausal women and men in the same age group. The plaque area remained 25 % smaller in both coronaries in postmenopausal women aged 51–70 years compared to men. In the oldest postmenopausal group (≥70 years), plaque area reached the level of men. In the postmenopausal period, coronary stenosis in the left anterior descending (LAD) artery remained lower among women.
We did not detect any major sex-difference in coronary atherosclerosis in the premenopausal period when women are considered to be protected from CHD. However, in line with CHD mortality statistics, postmenopausal women showed a slower speed of coronary atherosclerosis development compared to men.
Cilostazol addition to aspirin may worsen the short-term outcome in patients with large artery disease: ADS subanalysis
2024, Journal of the Neurological Sciences
Our previous acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of neurological deterioration in non-cardioembolic stroke patients. In this post-hoc analysis, we investigated whether the impact of dual antiplatelet therapy (DAPT) may depend on neurological severity, as represented by large artery disease.
Neurological deterioration was defined as neurological progression with an increment of the National Institutes of Health Stroke Scale (NIHSS) score of ≥2. NIHSS score subgroups were divided into that of 0–1, 2–4, 5–10, and >10.
Among 1014 patients, 203 (20%) had the large artery disease, and 811 (80%) did not. In the total cohort, the rate of neurological deterioration was 10.8% in the DAPT group and 8.3% in the aspirin group (P = 0.197). When we focused on the large artery disease group, DAPT group had a higher rate of neurological deterioration as 18.3% compared to 8.2% in the aspirin group (P = 0.036). Among patients with NIHSS score of 0–1 and 2–4, the rates of neurological deterioration were not different between the two group (both, P = 1.000). However, when NIHSS score elevated to 5–10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated (P = 0.013). Among the patients with NIHSS score of >10, 60% in the DAPT group and none (0%) in the aspirin group had the neurological deterioration (P = 0.045).
DAPT with aspirin and cilostazol was associated with higher rate of neurological deterioration when patients have large artery disease and not mild neurological deficits.
Sex differences in the genetic and molecular mechanisms of coronary artery disease
2023, Atherosclerosis
Sex differences in coronary artery disease (CAD) presentation, risk factors and prognosis have been widely studied. Similarly, studies on atherosclerosis have shown prominent sex differences in plaque biology. Our understanding of the underlying genetic and molecular mechanisms that drive these differences remains fragmented and largely understudied. Through reviewing genetic and epigenetic studies, we identified more than 40 sex-differential candidate genes (13 within known CAD loci) that may explain, at least in part, sex differences in vascular remodeling, lipid metabolism and endothelial dysfunction. Studies with transcriptomic and single-cell RNA sequencing data from atherosclerotic plaques highlight potential sex differences in smooth muscle cell and endothelial cell biology. Especially, phenotypic switching of smooth muscle cells seems to play a crucial role in female atherosclerosis. This matches the known sex differences in atherosclerotic phenotypes, with men being more prone to lipid-rich plaques, while women are more likely to develop fibrous plaques with endothelial dysfunction. To unravel the complex mechanisms that drive sex differences in CAD, increased statistical power and adjustments to study designs and analysis strategies are required. This entails increasing inclusion rates of women, performing well-defined sex-stratified analyses and the integration of multi-omics data.
Sex differences in diagnostic modalities of atherosclerosis in the macrocirculation
2023, Atherosclerosis
Asymptomatic atherosclerosis begins early in life and may progress in a sex-specific manner to become the major cause of cardiovascular morbidity and death. As diagnostic tools to evaluate atherosclerosis in the macrocirculation, we discuss imaging methods (in terms of computed tomography, positron emission tomography, intravascular ultrasound, magnetic resonance imaging, and optical coherence tomography), along with derived scores (Agatston, Gensini, Leaman, Syntax), and also hemodynamic indices of vascular stiffness (including flow-mediated dilation, shear stress, pulse pressure, augmentation index, arterial distensibility), assessment of plaque properties (composition, erosion, rupture), stenosis measures such as fractional flow reserve. Moreover, biomarkers including matrix metalloproteinases, vascular endothelial growth factors and miRNAs, as well as the impact of machine learning support, are described. Special attention is given to age-related aspects and sex-specific characteristics, along with clinical implications. Knowledge gaps are identified and directions for future research formulated.
Clinical factors distinguishing renal infarction from acute pyelonephritis: A randomly matched retrospective case-control study
2023, American Journal of Emergency Medicine
Renal infarction (RI) is rare but clinically important because the appropriate treatment depends on the time of diagnosis. RI is often misdiagnosed as acute pyelonephritis (APN) because both diseases have nonspecific symptoms such as flank pain and abdominal pain. We identified predictors for distinguishing RI from APN.
The data of patients visited the emergency department and diagnosed with RI or APN from March 2016 to May 2020 were prospectively collected and retrospectively analyzed. Patients aged under 18 years, with a history of trauma, or incomplete medical records were excluded. Using a matching ratio of 1:5, RI patients were randomly matched to APN patients. Multivariable logistic regression analysis was performed to identify factors that could distinguish RI from APN. In addition, we constructed a decision tree to identify patterns of risk factors and develop prediction algorithms.
The RI and APN groups included 55 and 275 patients, respectively. Multivariable logistic regression analysis showed that male sex (OR, 6.161; p = 0.009), atrial fibrillation (AF) (OR, 14.303; p = 0.021), costovertebral angle tenderness (CVAT) (OR, 0.106; p < 0.001), aspartate transaminase (AST) level > 21.50 U/L (OR, 19.820; p < 0.001), C-reactive protein (CRP) level < 19.75 mg/L (OR, 10.167; p < 0.001), and pyuria (OR, 0.037; p < 0.001) were significantly associated with RI distinguishing from APN.
Male sex, AF, no CVAT, AST level > 21.50 U/L, CRP level < 19.75 mg/L, and no pyuria were significant factors that could distinguish RI from APN.

View all citing articles on Scopus

View full text

ReviewSex differences in coronary artery disease: Pathological observations

Highlights

Abstract

Section snippets

Nonatherosclerotic coronary artery disease

Risk factors

Effect of menopause in coronary atherosclerosis

Acute myocardial infarction in women

Conclusions

Disclosures

Conflict of interest

J. Am. Coll. Cardiol.

Lancet

Lancet

Can. J. Cardiol.

Am. Heart J.

Am. Heart J.

J. Am. Coll. Cardiol.

Am. J. Pathol.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. Heart J.

Heart disease and stroke statistics–2013 update: a report from the American heart association

Circulation

Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults

JAMA: J. Am. Med. Assoc.

Fifteen-year trends in awareness of heart disease in women: results of a 2012 American heart association national survey

Circulation

Mechanisms of stress (Takotsubo) cardiomyopathy

Nat. Rev. Cardiol.

Spontaneous coronary artery dissection: aggressive vs. conservative therapy

J. Invasive Cardiol.

Takotsubo cardiomyopathy after cesarean: a case report and published work review of pregnancy-related cases

J. Obstetrics Gynaecol. Res.

Guidelines for cholesterol management: recommendations of the national cholesterol education Program's Adult treatment panel II

Heart Dis. Stroke: J. Prim. Care Physicians

Association between estrogen receptor alpha gene variation and cardiovascular disease

JAMA: J. Am. Med. Assoc.

Coronary risk factors and plaque morphology in men with coronary disease who died suddenly

N. Engl. J. Med.

Coronary risk factors and plaque morphology in men with coronary disease who died suddenly

N. Engl. J. Med.

Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women

Circulation

Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study

Circulation

Plaque rupture and sudden death related to exertion in men with coronary artery disease

JAMA: J. Am. Med. Assoc.

Review
Sex differences in coronary artery disease: Pathological observations