Hysterectomy and Risk of Cardiovascular Disease

Hysterectomy Status and Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study Wanda Nicholson MD, MPH, Keiko Asao MD, Josef Coresh MD, PhD, Frederick Brancati MD, MHS, Neil R. Powe, MD, MPH, MBA Johns Hopkins University School of Medicine Johns Hopkins Bloomberg School of Public Health Women and Cardiovascular Disease • Coronary heart disease (CHD) and stroke are major causes of morbidity and death among women • Hysterectomy is common surgical procedure • • • Primarily performed for benign disease Approximately 600,000 cases annually Higher average blood pressures Worse CVD risk profiles • Prior studies show hysterectomy associated with: • • • • • Limitations of current studies Few population-based Limited geographical areas CVD is composite outcome Howard B et. Al. Circulation, 2005; Settnes A, Eur J Ob,Gyn, and Repro Biology, 2005 Conceptual Model Hysterectomy and CVD Independent? Hysterectomy Demographics age, race, marital status, income, education, smoking, family history BP= blood pressure BMI= body mass index HRT=hormone replacement therapy OCP=oral contraceptive pills CHD Stroke CVD risk factors BP, sport index, lipids, caloric intake, BMI, sport index Reproductive factors Parity menopausal status HRT use OCP use Hypothesis and Objectives Hypothesis: hysterectomy has an independent association with CHD and stroke Objectives: determine incidence of CVD in hysterectomy groups • describe differences in risk factors for CVD between hysterectomy groups • estimate association of hysterectomy with CVD • identify confounding factors that might account for this association Study Design • Longitudinal (cohort) study of African-American and White women • The Atherosclerosis Risk in Communities (ARIC) Study • • • • prospective epidemiological study of 15,792 adult men and women, aged 45 to 64 years at baseline recruitment between 1986 and 1989 four U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; Suburban Minneapolis; and Washington County, Maryland average 9.1 years of follow-up Study Design • Study sample: 7,399 women • Exposure: Hysterectomy status • • • no hysterectomy or oophorectomy hysterectomy alone or with unilateral oophorectomy hysterectomy with bilateral oophorectomy • Outcomes: incident CHD and stroke Statistical Analysis • Analysis I • Incident rates of CHD and stroke by hysterectomy status • Analysis II • Cox proportional regression analysis • estimate association of hysterectomy with incident CHD and stroke • Covariates • Demographics: age, race, income, education, family history • Clinical: Hypertension, diabetes, lipids, BMI, smoking status • Reproductive: parity, menopause status, birth control and hormone replacement therapy use Selected Characteristics at Baseline Characteristics ┼ No Hyst Hyst alone/USO Hyst/BSO n=4,596 n=1,529 n=1,274 Age (yrs.) Black, % Income < $16K, % Parity % (none) 1 or more ┼ 53.5 ± 5.7 25 24 8 92 --46 5.4 ± 5.6 33* 27* 5 95* 39.3 ± 6.5 49* 54.0* ± 5.4 46* 34* 9 91* 42.3 ± 7.3 45* Age at hyst Smoking,% (current or past) Ever use HRT, % 78 53* 27* **No-hysterectomy group does not include women who underwent bilateral oophorectomy without hysterectomy * p<0.05 compared to “No Hysterectomy” group by Tukey’s Studentized range test for continuous variables and chi-squared test for categorical variables. ┼Reported as mean (standard deviation) Selected Characteristics at Baseline Characteristics ┼ No Hyst 27.7± 6.2 2.34 (0.76) 10 31 5.0 (1.09) BMI Sport index Hyst alone/USO 27.8 ± 5.8 2.31 (0.73) 10 35 * 5.6* (1.15) Hyst/BSO 28.7 ± 6.1 2.26 * (0.74) 15 * 43 * 5.8* (1.15) ┼ Diabetes, % Hypertension, % ┼ Total cholesterol ┼ Triglycerides 1.35 (0.85) 40 1.44* (0.94) 43 1.49* (0.90) 41 Family history, % No-hysterectomy group =no removal of uterus or ovaries; * p<0.05 compared to “No Hysterectomy” group by Tukey’s Studentized range test for continuous variables and chi-squared test for categorical variables ┼Reported as mean (standard deviation); Cholesterol and triglycerides reported as mmol/L Incident CHD and Stroke Outcome Incident CHD (n) Incidence rate* No Hyst 312 5.0 (4.5, 5.6) Hyst alone or USO ┼ 108 5.3 (4.4, 6.4) Hyst with BSO ┼ 99 5.8 (4.8, 7.1) Incident Stroke (n) Incidence rate* 144 2.3 (1.9, 2.7) 57 2.7 (2.1, 3.6) 58 3.4 (2.6-4.4) ┼ ┼ Hyst alone or USO = hysterectomy alone or with removal of one ovary; with BSO = hysterectomy with removal of both ovaries * Per 1,000 p-y Hyst Hysterectomy and Risk of CHD Coronary Heart Disease Unadjusted model Adjusted model* ┼ Hyst alone or USO┼ HR (95% CI) 1.02 (0.81, 1.27) 0.88 (0.68, 1.14) Hyst with BSO┼ HR (95% CI) 1.12 (0.89, 1.42) 0.82 (0.62, 1.09) Hyst alone or USO = hysterectomy alone or with removal of one ovary; ┼ Hyst with BSO = hysterectomy with removal of both ovaries HR = hazard ratio; 95% CI = 95 % Confidence Interval *Model adjusted for age, race, income, education, family history, hypertension, diabetes, lipids, BMI, smoking status, parity, menopause status, birth control and HRT use Hysterectomy and Risk of Stroke Incident stroke Hyst alone or USO┼ HR (95% CI) 1.18 (0.86, 1.60) 1.09 (0.76, 1.57) Hyst with BSO┼ HR (95% CI) 1.50 (1.10, 2.04) 1.17 (0.80, 1.71) Unadjusted model Adjusted model* ┼ Hyst alone or USO = hysterectomy alone or with removal of one ovary; ┼ Hyst with BSO = hysterectomy with removal of both ovaries HR = hazard ratio; 95% CI = 95 % Confidence Interval *Model adjusted for age, race, income, education, family history, hypertension, diabetes, lipids, BMI, smoking status, parity, menopause status, birth control and HRT use Conclusions • Women with hysterectomy have a worse CVD risk profile • • Blood pressure and cholesterol levels Lower physical activity • Hysterectomy associated with higher risk for stroke, but not CHD in unadjusted analysis • After adjustment for confounders, risk of stroke with hysterectomy is attenuated and not significant Limitations • Sample is limited to African-American and white women • Insufficient power for race-specific analysis • Hysterectomy status based on self-report • No adjustment for physiologic measures related to CVD Strengths • Population-based sample • Established method for data collection and clinical measures • Prospective study with an average of 9.1 years of follow-up Policy Implications • Hysterectomy and conditions leading to this procedure deserve further attention as a potential risk factor for CVD • Future research should focus on     confirmation of findings in longer follow-up studies mechanism of effect of hysterectomy on development of CVD risk factors development of strategies for surveillance of CVD risk factors in women undergoing hysterectomy collaboration between primary care and gynecologic practitioners Acknowlegements • Co-authors  Keiko Asao  Josef Coresh  Frederick Brancati  Neil R. Powe • ARIC Publications Committee • Funding Sources supported through NHLBI  NIDDK  ARIC Stepwise Model Hysterectomy and Stroke Incident stroke Model 1 Model 2 Covariates Hyst alone/USO Hyst/BSO None 1.20 (0.88, 1.63) 1.50 (1.10, 2.04) 1.19 (0.86, 1.65) Demographics 1.12 (0.80,1.56) Model 3 Model 4 Model 2 + clinical factors Model 3 + reproductive factors 1.11 (0.77, 1.54) 1.12 (0.79, 1.60) 1.18 (0.85, 1.64) 1.25 (0.86,1.80) Demographics: age, race, income, education, family history; Clinical: hypertension, diabetes, cholesterol, triglycerides, BMI, smoking; Reproductive: parity, hormone therapy, oral contraceptive use