Subramaniam Karthik1, V P Vipin2, Aditya Kapoor3, Archana Tripathi4, Manoj Shukla4, Preeti Dabadghao4. 1. Department of Endocrinology, Silverline Hospital, Kochi, India. 2. Department of Endocrinology, Aster Medcity, Kochi, India. 3. Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. 4. Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Abstract
STUDY QUESTION: Do the siblings of Asian Indian women with polycystic ovary syndrome (PCOS) manifest increased cardiovascular disease (CVD) risk by carotid intima-media thickness (CIMT) and brachial artery flow-mediated dilatation (FMD)? SUMMARY ANSWER: Siblings had functional endothelial dysfunction (FMD was reduced) when compared to age and BMI-matched controls while sisters but not brothers had structural endothelial dysfunction (CIMT was increased). WHAT IS KNOWN ALREADY: Siblings of women with PCOS have increased metabolic risk but it varies with ethnicity. Among Asian Indians the only previous study has shown reduced FMD in brothers. STUDY DESIGN, SIZE, DURATION: This study was a tertiary care hospital-based cross-sectional case control study in the outpatient department of the endocrine clinic over 18 months. In total, 41 brothers and 35 sisters of women with PCOS (diagnosed by 2003 Rotterdam criteria) were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS: Age (±2 years), sex and BMI- (±1 kg/m2) matched controls were selected. Cases and controls underwent clinical and biochemical investigations. Cardiologists performed doppler ultrasonogram to determine CIMT and FMD in a blinded fashion. MAIN RESULTS AND THE ROLE OF CHANCE: FMD was decreased in brothers [median 12.3% interquartile range (5.1, 19) versus 18.4% (12.6, 21.5), P = 0.002] and in sisters [10.8% (5.8, 17.2) versus 14.7% (11.4, 18.2), P = 0.027] when compared to controls. CIMT was higher in sisters [median 0.4 mm (0.35, 0.5) versus 0.3 mm (0.3, 0.4), P= 0.002] when compared to controls but not in brothers. Metabolic syndrome was more common in brothers (27% versus 5% in controls, P = 0.007) even after matching for age and BMI. Insulin resistance (homeostatic model assessment for insulin resistance and acanthosis) was higher in brothers as compared to controls. Dehydroepiandrosterone sulphate was significantly elevated in brothers. LIMITATIONS, REASONS FOR CAUTION: There may have been referral bias of patients with PCOS in a tertiary care institute, and the radiological assessment was performed by two cardiologists serially on different time frames over the study duration. Power was only 50% in CIMT for brothers. WIDER IMPLICATIONS OF THE FINDINGS: Siblings of women with PCOS had higher CVD risk over and above the already pre-existing higher metabolic risk associated with Asian Indian ethnicity and therefore the siblings require vigilant management. Endothelial dysfunction and insulin resistance seems to be a heritable trait of PCOS independent of obesity, which if confirmed in other ethnicities would have important implications. STUDY FUNDING/COMPETING INTEREST(S): Funded by Intramural Research Grant (PGI/DIR/RC/943/2013) from the Sanjay Gandhi Postgraduate Institute of Medical Sciences. No competing interests.
STUDY QUESTION: Do the siblings of Asian Indian women with polycystic ovary syndrome (PCOS) manifest increased cardiovascular disease (CVD) risk by carotid intima-media thickness (CIMT) and brachial artery flow-mediated dilatation (FMD)? SUMMARY ANSWER: Siblings had functional endothelial dysfunction (FMD was reduced) when compared to age and BMI-matched controls while sisters but not brothers had structural endothelial dysfunction (CIMT was increased). WHAT IS KNOWN ALREADY: Siblings of women with PCOS have increased metabolic risk but it varies with ethnicity. Among Asian Indians the only previous study has shown reduced FMD in brothers. STUDY DESIGN, SIZE, DURATION: This study was a tertiary care hospital-based cross-sectional case control study in the outpatient department of the endocrine clinic over 18 months. In total, 41 brothers and 35 sisters of women with PCOS (diagnosed by 2003 Rotterdam criteria) were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS: Age (±2 years), sex and BMI- (±1 kg/m2) matched controls were selected. Cases and controls underwent clinical and biochemical investigations. Cardiologists performed doppler ultrasonogram to determine CIMT and FMD in a blinded fashion. MAIN RESULTS AND THE ROLE OF CHANCE: FMD was decreased in brothers [median 12.3% interquartile range (5.1, 19) versus 18.4% (12.6, 21.5), P = 0.002] and in sisters [10.8% (5.8, 17.2) versus 14.7% (11.4, 18.2), P = 0.027] when compared to controls. CIMT was higher in sisters [median 0.4 mm (0.35, 0.5) versus 0.3 mm (0.3, 0.4), P= 0.002] when compared to controls but not in brothers. Metabolic syndrome was more common in brothers (27% versus 5% in controls, P = 0.007) even after matching for age and BMI. Insulin resistance (homeostatic model assessment for insulin resistance and acanthosis) was higher in brothers as compared to controls. Dehydroepiandrosterone sulphate was significantly elevated in brothers. LIMITATIONS, REASONS FOR CAUTION: There may have been referral bias of patients with PCOS in a tertiary care institute, and the radiological assessment was performed by two cardiologists serially on different time frames over the study duration. Power was only 50% in CIMT for brothers. WIDER IMPLICATIONS OF THE FINDINGS: Siblings of women with PCOS had higher CVD risk over and above the already pre-existing higher metabolic risk associated with Asian Indian ethnicity and therefore the siblings require vigilant management. Endothelial dysfunction and insulin resistance seems to be a heritable trait of PCOS independent of obesity, which if confirmed in other ethnicities would have important implications. STUDY FUNDING/COMPETING INTEREST(S): Funded by Intramural Research Grant (PGI/DIR/RC/943/2013) from the Sanjay Gandhi Postgraduate Institute of Medical Sciences. No competing interests.