Department of Endocrinology, Silverline Hospital, Kochi, India.
Department of Endocrinology, Aster Medcity, Kochi, India.
Hum Reprod. 2019 Aug 1;34(8):1559-1566. doi: 10.1093/humrep/dez104.
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)?
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).
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.
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.
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.
多囊卵巢综合征（PCOS）女性的兄弟姐妹是否通过颈动脉内膜中层厚度（CIMT）和肱动脉血流介导的扩张（FMD）表现出心血管疾病（CVD）风险增加？
与年龄和 BMI 匹配的对照组相比，兄弟姐妹存在功能性内皮功能障碍（FMD 降低），而仅姐妹存在结构性内皮功能障碍（CIMT 增加）。
PCOS 女性的兄弟姐妹存在代谢风险增加，但存在种族差异。在亚洲印第安人中，唯一的先前研究表明兄弟的 FMD 降低。
研究设计、规模、持续时间：这是一项三级保健医院为基础的门诊内分泌诊所的横断面病例对照研究，持续了 18 个月。总共招募了 41 名 PCOS 女性的兄弟和 35 名姐妹（根据 2003 年鹿特丹标准诊断）。
参与者/材料、地点、方法：选择年龄（±2 岁）、性别和 BMI（±1kg/m2）匹配的对照组。病例和对照组接受了临床和生化检查。心脏病专家以盲法方式进行多普勒超声检查以确定 CIMT 和 FMD。
与对照组相比，兄弟的 FMD 降低[中位数 12.3%（5.1，19）与 18.4%（12.6，21.5），P=0.002]，姐妹的 FMD 也降低[中位数 10.8%（5.8，17.2）与 14.7%（11.4，18.2），P=0.027]。与对照组相比，姐妹的 CIMT 更高[中位数 0.4mm（0.35，0.5）与 0.3mm（0.3，0.4），P=0.002]，但兄弟的 CIMT 没有增加。代谢综合征在兄弟中更为常见（27%与对照组的 5%，P=0.007），即使在年龄和 BMI 匹配后也是如此。与对照组相比，兄弟的胰岛素抵抗（稳态模型评估的胰岛素抵抗和棘皮症）更高。脱氢表雄酮硫酸盐在兄弟中显著升高。
局限性、谨慎的原因：在三级保健机构中，PCOS 患者可能存在转诊偏倚，并且在研究期间，放射学评估由两名心脏病专家在不同的时间框架上连续进行。在兄弟中，CIMT 的功率仅为 50%。
PCOS 女性的兄弟姐妹的 CVD 风险高于已经存在的与亚洲印第安人种族相关的更高的代谢风险，因此兄弟姐妹需要进行警惕性管理。内皮功能障碍和胰岛素抵抗似乎是 PCOS 的遗传特征，独立于肥胖，如果在其他种族中得到证实，将具有重要意义。
研究资助/利益冲突：由 Sanjay Gandhi 研究生医学科学研究所的内部研究拨款（PGI/DIR/RC/943/2013）资助。没有竞争利益。
