Original Article
Women With Early Menopause Have Higher Rates of Target Lesion Revascularization After Percutaneous Coronary Intervention
Angiology 1-6 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715589247 ang.sagepub.com
Linlin Zhang, MD1, Zhijian Wang, MD1, Xiaoli Liu, MD1, Zhiming Zhou, MD1, Yingxin Zhao, MD1, Dongmei Shi, MD1, Yuyang Liu, MD1, Jing Liang, MD1, Lixia Yang, MD1, Meng Chai, MD1, and Yujie Zhou, MD, PhD1
Abstract Early menopause has been found to be associated with higher risk of cardiovascular disease. Our objective was to investigate the impact of early menopause on clinical outcomes for women undergoing percutaneous coronary intervention (PCI). We observed female patients with coronary artery disease (CAD) undergoing PCI and found that women with early menopause (46 years old) were more likely to have CAD risk factors and more severe coronary lesions. During the 18-month follow-up, early menopause was associated with similar risk of death and myocardial infarction but higher risk of target lesion revascularization (TLR; 7.8% vs 5.3%, P ¼ .003) and major adverse cardiovascular events (MACEs; 11.3% vs 9.0%, P ¼ .007). After adjustment, early menopause was an independent risk factor for 18-month MACEs (hazard ratio [HR], 1.54; 95% confidence interval [CI] 1.18-2.00) and TLR (HR 1.61; 95% CI 1.21-2.13). In conclusion, for women undergoing PCI, early menopause is associated with higher risk of MACE, which is mainly driven by risk of TLR. Keywords early menopause, percutaneous coronary intervention, outcome
Introduction A rise in incidence of coronary artery disease (CAD) after the menopause and an increase in the severity of the presenting disease have been documented.1-5 Many studies reported that early menopause (EM) was associated with higher risk of cardiovascular (CV) diseases, heart failure, and mortality, which was independent of ethnicity and traditional risk factors.6-10 The risk of adverse outcomes increased with earlier age at the time of menopause.5,11-14 Every 1-year increase in age at menopause was reported to be associated with a mild but significant decreased hazard of incident heart failure in postmenopausal women.8 Although the adverse effect of EM has been widely reported, we know less on whether EM confers worse clinical outcomes in patients with established CAD, particularly those undergoing percutaneous coronary intervention (PCI). Therefore, we investigated the prevalence of EM in postmenopause female patients undergoing PCI and to compare the difference between EM and normal menopause (NM) in terms of baseline characteristics, clinical presentation, inhospital, and long-term outcomes.
Methods Population We screened female patients who were admitted in our hospital with CAD as initial diagnosis and underwent PCI from January 2010 to December 2012. Menopause status was evaluated in all these patients, and only women with postmenopausal status were included in this study. Those with perimenopause, premenopause, or those without accurate menstruation records were excluded. Other exclusion criteria included acute myocardial
1
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China
Corresponding Author: Yujie Zhou, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China. Email: [email protected]
Downloaded from ang.sagepub.com at FLORIDA INTERNATIONAL UNIV on November 13, 2015
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Angiology
infarction (MI), the detection of a rise in alanine aminotransferase/aspartate aminotransferase values with 5 times more above the 99th percentile upper reference limit, glomerular filtration rate < 60 mL/min per 1.73 m2, history of malignant disease, hematological system disease, and immune system disease. The menopause was defined as women not having experienced any menstrual flow for a minimum of 12 months.15 In our study, myocardial infarction was diagnosed according to the third universal definition.16 All patients were divided into 2 groups according to their menopause age: EM group (menopause age 46 years) and NM group (menopause age > 46 years). The study was approved by the institutional ethics committees at Beijing Anzhen Hospital and Capital Medical University, Beijing, China. All patients provided written informed consent.
Data Collection The information on demographic characteristics, risk factors, laboratory values, and angiographic variables was derived from patients’ files. Family history of CAD was defined as having a self-reported history of a first-degree relative (parent, sibling, or child) with heart attack. Ever smoking was as having smoked 100 or more cigarettes in a lifetime. Diabetes mellitus (DM) was defined as a fasting plasma glucose level 7.0 mmol/L (126 mg/dL), 2 hour-postprandial plasma glucose 11.1 mmol/L (200 mg/dL), casual plasma glucose 11.1 mmol/L (200 mg/dL), glycated hemoglobin 6.5%, and/or hypoglycemic therapy.17 Hypertension was defined as a systolic blood pressure (BP) > 140 mm Hg, diastolic BP >90 mm Hg (Joint National Committee VI18), or self-report of hypertension plus the use of antihypertensive medication.
stenosis within the stent or within 5-mm border proximal or distal to the stent, including PCI or coronary artery bypass grafting (CABG). The second end point was thrombolysis in myocardial infarction (TIMI) major bleeding, which was defined as intracranial hemorrhage or a 5 g/dL decrease in hemoglobin concentration or a 15% absolute decrease in hematocrit.20 Clinical follow-up was performed by either telephone contact or office visit. Investigators blinded to patient menopausal status performed follow-up interviews and medical event classification. If a patient had >1 procedure during the study period, only the initial procedure was included.
Statistical Analysis Continuous variables are presented as mean and standard deviation and were compared using Student t test. Categorical variables between the 2 groups were compared using chi-square and presented as frequencies and percentages. Event-free survival estimates were created using Kaplan-Meier methods and compared to the log-rank test with respect to menopausal status. Independent predictors of end points were identified using Cox proportional hazards regression model with forward variable selection with entry and exit criteria of a P < .10. Then, the remaining variables were refitted into the model manually to ensure all the confounders of EM were included. The candidate variables entered in the model included age, EM, previous MI, previous CABG, previous PCI, hypertension, DM, diastolic BP, bifurcation lesions, triple-vessel diseases, length of stent >20 mm, and diameter of stent
Women With Early Menopause Have Higher Rates of Target Lesion Revascularization After Percutaneous Coronary Intervention
Angiology 1-6 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715589247 ang.sagepub.com
Linlin Zhang, MD1, Zhijian Wang, MD1, Xiaoli Liu, MD1, Zhiming Zhou, MD1, Yingxin Zhao, MD1, Dongmei Shi, MD1, Yuyang Liu, MD1, Jing Liang, MD1, Lixia Yang, MD1, Meng Chai, MD1, and Yujie Zhou, MD, PhD1
Abstract Early menopause has been found to be associated with higher risk of cardiovascular disease. Our objective was to investigate the impact of early menopause on clinical outcomes for women undergoing percutaneous coronary intervention (PCI). We observed female patients with coronary artery disease (CAD) undergoing PCI and found that women with early menopause (46 years old) were more likely to have CAD risk factors and more severe coronary lesions. During the 18-month follow-up, early menopause was associated with similar risk of death and myocardial infarction but higher risk of target lesion revascularization (TLR; 7.8% vs 5.3%, P ¼ .003) and major adverse cardiovascular events (MACEs; 11.3% vs 9.0%, P ¼ .007). After adjustment, early menopause was an independent risk factor for 18-month MACEs (hazard ratio [HR], 1.54; 95% confidence interval [CI] 1.18-2.00) and TLR (HR 1.61; 95% CI 1.21-2.13). In conclusion, for women undergoing PCI, early menopause is associated with higher risk of MACE, which is mainly driven by risk of TLR. Keywords early menopause, percutaneous coronary intervention, outcome
Introduction A rise in incidence of coronary artery disease (CAD) after the menopause and an increase in the severity of the presenting disease have been documented.1-5 Many studies reported that early menopause (EM) was associated with higher risk of cardiovascular (CV) diseases, heart failure, and mortality, which was independent of ethnicity and traditional risk factors.6-10 The risk of adverse outcomes increased with earlier age at the time of menopause.5,11-14 Every 1-year increase in age at menopause was reported to be associated with a mild but significant decreased hazard of incident heart failure in postmenopausal women.8 Although the adverse effect of EM has been widely reported, we know less on whether EM confers worse clinical outcomes in patients with established CAD, particularly those undergoing percutaneous coronary intervention (PCI). Therefore, we investigated the prevalence of EM in postmenopause female patients undergoing PCI and to compare the difference between EM and normal menopause (NM) in terms of baseline characteristics, clinical presentation, inhospital, and long-term outcomes.
Methods Population We screened female patients who were admitted in our hospital with CAD as initial diagnosis and underwent PCI from January 2010 to December 2012. Menopause status was evaluated in all these patients, and only women with postmenopausal status were included in this study. Those with perimenopause, premenopause, or those without accurate menstruation records were excluded. Other exclusion criteria included acute myocardial
1
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China
Corresponding Author: Yujie Zhou, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China. Email: [email protected]
Downloaded from ang.sagepub.com at FLORIDA INTERNATIONAL UNIV on November 13, 2015
2
Angiology
infarction (MI), the detection of a rise in alanine aminotransferase/aspartate aminotransferase values with 5 times more above the 99th percentile upper reference limit, glomerular filtration rate < 60 mL/min per 1.73 m2, history of malignant disease, hematological system disease, and immune system disease. The menopause was defined as women not having experienced any menstrual flow for a minimum of 12 months.15 In our study, myocardial infarction was diagnosed according to the third universal definition.16 All patients were divided into 2 groups according to their menopause age: EM group (menopause age 46 years) and NM group (menopause age > 46 years). The study was approved by the institutional ethics committees at Beijing Anzhen Hospital and Capital Medical University, Beijing, China. All patients provided written informed consent.
Data Collection The information on demographic characteristics, risk factors, laboratory values, and angiographic variables was derived from patients’ files. Family history of CAD was defined as having a self-reported history of a first-degree relative (parent, sibling, or child) with heart attack. Ever smoking was as having smoked 100 or more cigarettes in a lifetime. Diabetes mellitus (DM) was defined as a fasting plasma glucose level 7.0 mmol/L (126 mg/dL), 2 hour-postprandial plasma glucose 11.1 mmol/L (200 mg/dL), casual plasma glucose 11.1 mmol/L (200 mg/dL), glycated hemoglobin 6.5%, and/or hypoglycemic therapy.17 Hypertension was defined as a systolic blood pressure (BP) > 140 mm Hg, diastolic BP >90 mm Hg (Joint National Committee VI18), or self-report of hypertension plus the use of antihypertensive medication.
stenosis within the stent or within 5-mm border proximal or distal to the stent, including PCI or coronary artery bypass grafting (CABG). The second end point was thrombolysis in myocardial infarction (TIMI) major bleeding, which was defined as intracranial hemorrhage or a 5 g/dL decrease in hemoglobin concentration or a 15% absolute decrease in hematocrit.20 Clinical follow-up was performed by either telephone contact or office visit. Investigators blinded to patient menopausal status performed follow-up interviews and medical event classification. If a patient had >1 procedure during the study period, only the initial procedure was included.
Statistical Analysis Continuous variables are presented as mean and standard deviation and were compared using Student t test. Categorical variables between the 2 groups were compared using chi-square and presented as frequencies and percentages. Event-free survival estimates were created using Kaplan-Meier methods and compared to the log-rank test with respect to menopausal status. Independent predictors of end points were identified using Cox proportional hazards regression model with forward variable selection with entry and exit criteria of a P < .10. Then, the remaining variables were refitted into the model manually to ensure all the confounders of EM were included. The candidate variables entered in the model included age, EM, previous MI, previous CABG, previous PCI, hypertension, DM, diastolic BP, bifurcation lesions, triple-vessel diseases, length of stent >20 mm, and diameter of stent
