At the Fifth Annual Heart in Diabetes (HiD) Conference, held in New York 10-12 September 2021, a variety of topics were addressed related to the cardiovascular disease (CVD) risks and CV complications of diabetes. This is the first of a two-part summary of some of the presentations at the meeting, reviewing risk factors.

Brendan Everett, Boston, MA, reviewed a biomarker approach to risk stratification, pointing out that age, sex, cigarette use, blood pressure, total and high-density lipoprotein (HDL) cholesterol, a variety of markers of glycemia, and use of aspirin, statins, and antihypertensive agents can all be considered markers to be used in assessment of atherosclerotic CVD (ASCVD) risk, with familial hypercholesterolemia and family history of premature CVD, and elevated triglyceride, apolipoprotein B, and lipoprotein (a) levels additional factors. He termed high-sensitivity cardiac troponin (hs-cTnT), C-reactive protein (hsCRP), and B-type natriuretic peptides, such as the N-terminal prohormone of brain natriuretic peptide (NT-proBNP), novel “risk enhancing factors.” Everett compared these with the coronary artery calcium (CAC) score in guiding discussion of risk and of intensity of therapy with patients having borderline or intermediate (5%-20%) 10-year event rate risk. He showed evidence using the C-statistic, the area under the curve of sensitivity vs specificity, that NT-proBNP gives modest additional improvement in ASCVD risk prediction, similar to that of the CAC score.1, 2 Ambarish Pandey, Dallas, TX, discussed the identification of persons with diabetes at risk for heart failure based on hs-cTnT, NT-proBNP, hsCRP, and left ventricular hypertrophy on the electrocardiogram, showing that having two or more of these markers abnormal vs just one, and using this information to initiate sodium-glucose cotransporter-2 inhibitors (SGLT2i), would allow prevention of 103 heart failure events per 1000 persons over a decade.3 Norman Lepore, Los Angeles, CA, expanded on the discussion of use of risk markers and risk factors to allow personalization of risk for a given individual. CAC screening, he suggested, gives a specific and reproducible means of assessing risk, mechanistically based on production of a variety of local factors in the inflamed atherosclerotic plaque, including bone morphogenetic protein, leading to ectopic bone formation. The CAC score can be used in recommending statin and aspirin therapy and in recommending higher or lower statin intensity.4

Leslee Shaw, New York, NY, reviewed evidence that risk scores may be less useful in women in the identification of ASCVD, pointing out that the commonly accepted 7.5% 10-year risk threshold would lead to nearly a two thirds reduction in statin use for women. The finding of a positive CAC test in women as an index both of atherosclerotic plaque and of the likelihood of more extensive CVD, although lower than that in men, is still sizable and increases in prevalence after menopause.5 Furthermore, nonobstructive CAD prevalence is greater in women than in men6 and is associated with plaque erosion leading to thrombus formation, increasing risk of adverse outcome.7 Use of computed tomography (CT) angiogram-guided treatment to increase use of antiplatelet agents and statins improves outcome,8 further evidence of the importance of imaging approaches.

Matthew Budoff, Los Angeles, CA, discussed a variety of noninvasive technologies as options for assessment of CV risk of asymptomatic persons with diabetes. He opined that the exercise tolerance test (ETT) has more false positive than true positive results, making it not useful for this purpose, that carotid intima-media thickness (IMT) has low cost but poor reproducibility, although the finding of an atherosclerotic plaque is important evidence of CVD. CT and magnetic resonance imaging coronary angiography have not been widely studied, and the echocardiographic ETT does not have favorable evidence of benefit in screening asymptomatic patients, leading him to conclude that the strongest evidence is in support of CAC measurement. Compared with a clinical risk score alone, CAC score improves discrimination of CVD risk more than the ankle-brachial index, hsCRP, or carotid IMT,9 particularly among persons with diabetes,10 and Budoff showed evidence from his study of adults with diabetes that there is a direct relationship between the CAC score and total and CV mortality rates. He also pointed out the usefulness of biomarkers such as albuminuria and NT-proBNP in assessment of risk in type 2 diabetes (T2D), stressing the importance of imaging in disease prevention rather than treatment of disease that has already become full blown.

Elizabeth Selvin, Baltimore, MD, discussed issues of the associations of obesity and diabetes with heart failure, reviewing the strong evidence from the Atherosclerosis Risk In Communities (ARIC) Study of a nonlinear relationship of diabetes duration with heart failure risk, particularly during the first decade of the disease, as well as the (lesser) increase in heart failure risk associated with prediabetes.11 She reviewed further ARIC studies using hs-cTnT, which may reflect chronic subclinical myocardial damage. In asymptomatic persons without CVD history, hs-cTnT ≥14 ng/L was associated with 6-fold, 4-fold, and 2.3-fold increases in likelihoods of heart failure, total mortality, and coronary heart disease (CHD).12, 13 Her studies further showed diabetes and prediabetes associations with elevated hs-cTnT. This relationship is further influenced by obesity, with body mass index and hs-cTnT independently associated with heart failure.14 Furthermore, in 17-year follow-up of 9477 persons in the ARIC population, “metabolically healthy” obesity was associated with higher overall CVD risk and, in particular, with higher heart failure risk in comparison with metabolically healthy normal weight. Erin Michos, Baltimore, MD, reviewed data from the Multiethnic Study of Atherosclerosis (MESA) showing direct relationships between the development of heart failure and atherosclerotic CVD and duration of hyperlipidemia.15 Similarly, with increasing duration of obesity,16 there is increasing risk of heart failure, each decade of obesity associated with a 20-30% increase in likelihood of elevated hs-cTnT,17 suggesting what Michos termed “long-term toxic effects of adiposity on the myocardium.”

Erica Gunderson, Oakland, CA, discussed interrelationships between gestational diabetes (GDM), subsequent glucose intolerance, and CAC development. She noted that GDM develops in 10%-12% of women in the United States, and 17-20% of women worldwide, with 20-50% of women who have had GDM subsequently developing T2D, and with a history of GDM associated with a 1.7-3.0-fold increase in risk of CVD. She showed a recently published analysis from the Coronary Artery Risk Development in Young Adults (CARDIA) study, in which women who had had GDM had increased risk of CAC at 15-25 year follow-up, even without subsequent development of diabetes, related to other risk factors, dyslipidemia, hypertension, and cigarette use.18 Gunderson commented on the need to enhance the follow-up of women who have had GDM, not only for subsequent diabetes, but also for intervention on these other CV risk factors.

Andrea Dunaif, New York, NY, discussed the polycystic ovary syndrome (PCOS), noting that approximately 70% of women with PCOS have a phenotype of metabolic risk with visceral obesity, with low HDL cholesterol, and with some elevation in low-density lipoprotein cholesterol related to hyperandrogenemia, associated with insulin resistance and with a 4-fold increase likelihood of diabetes, independent of weight, although obesity is present in 50%-80% of women with PCOS.19 PCOS is a strong risk factor for CVD. A useful question for population screening is ascertainment of whether a women has fewer than six menses annually, and Dunaif noted that having a menstrual cycle length of 40 days or more is associated with a 2.18-fold increase in development of diabetes20 and a 1.53-fold increase in likelihood of CVD events,21 although Dunaif pointed out that published studies are typically not of sufficient duration for CVD events to become prevalent. Michos gave a second presentation, addressing the impact of changes in sex hormones on CVD and heart failure, pointing out the well-recognized increase in CVD in women after menopause, tracking with elevation in free testosterone, which in turn is associated with greater left ventricular mass,22 with higher levels of NT-proBNP,23 with CAC progression,24 and with greater likelihood of CHD and heart failure.25 Lower levels of dehydroepiandrosterone sulfate (DHEA-S) in postmenopausal women are also associated with development of heart disease, further underscoring the complexity of the androgen–heart disease relationship.26 In men, in contrast, lower levels both of DHEA-S and of testosterone are generally associated with greater risk of CVD27 and of heart failure,28 although administration of testosterone may increase coronary artery plaque volume,29 which has led to a Food and Drug Administration Drug Safety Communication about using testosterone because of possible increased CVD event risk.30

在2021年9月10日至12日于纽约举行的第五届糖尿病心脏病(HiD)年会上，讨论了与糖尿病心血管疾病(CVD)风险和心血管并发症相关的各种话题。本文摘录会议的第一部分内容，主要回顾风险因素。

马萨诸塞州波士顿的Brendan Everett回顾了一种风险分层的生物标志物方法，指出年龄、性别、吸烟、血压、总和高密度脂蛋白胆固醇(HDL)、各种血糖标志物，阿司匹林、他汀类药物和降压药的使用，有家族高胆固醇血症和早产儿心血管疾病家族史，甘油三酯、载脂蛋白B、以及脂蛋白a升高等因素，都可以被认为是用于评估动脉粥样硬化性心血管疾病(ASCVD)风险的标志物，他将高敏心肌肌钙蛋白(hs-cTnT)、C反应蛋白(HsCRP)和B型利钠肽，如脑钠素N端前激素(NTproBNP)，称为新的“风险增强因子”。Everett将这些与冠状动脉钙化(CAC)评分进行比较，以指导对具有临界或中等(5%-20%)风险在10年内发生CVD的患者进行风险和治疗强度的管理。他以C统计量(敏感度与特异度曲线下的面积)说明NT-proBNP在ASCVD风险预测方面有额外改善，与CAC评分相似。德克萨斯州达拉斯的Ambarish Pandey讨论了根据hs-cTnT、nt-proBNP、hsCRP和心电图上的左心室肥厚来识别糖尿病患者心力衰竭的风险，并根据这些信息使用钠-葡萄糖协同转运体-2抑制剂(SGLT2i)，可以在十年内防止每1000人中发生103起心力衰竭事件。加利福尼亚州洛杉矶的Norman Lepore进一步讨论了风险标记物和风险因素的使用，以允许特定个人的风险个性化预测。他认为，CAC筛查提供了一种特异性和可重复性的风险评估手段，其机制是在炎症的动脉粥样硬化斑块中产生多种局部因子，包括骨形态发生蛋白，从而导致异位骨化。CAC评分可用于推荐他汀类药物和阿司匹林治疗，以及指导使用他汀类药物强度。

纽约州Leslee Shaw回顾了风险评分在女性ASCVD识别中可能不那么有用的证据，指出常用的7.5%风险阈值将导致女性他汀类药物使用量减少近三分之二。此外发现在女性中CAC试验阳性，可以作为动脉粥样硬化斑块和更广泛的心血管疾病可能性的一个指标，尽管可能性低于男性，但仍然是较大的，且在绝经后患病率增加。而女性非梗阻性冠心病患病率高于男性。它与斑块侵蚀导致血栓形成有关，增加了不良结局的风险。使用CT血管造影引导的治疗增加抗血小板药物和他汀类药物的使用可改善预后，进一步证明了成像方法的重要性。

加利福尼亚州洛杉矶的Matthew Budoff讨论了各种非侵入性技术，作为评估无症状糖尿病患者心血管风险的选择。他认为，运动耐量试验(ETT)的假阳性多于真阳性，对此没有用处，尽管发现动脉粥样硬化斑块是心血管疾病的重要证据。颈动脉内膜-中层厚度(IMT)检查成本低，但重复性差。CT和磁共振成像冠状动脉造影还没有得到广泛的研究，超声心动图ETT在筛查无症状患者方面没有有利的证据，他得出结论，最有力的证据支持CAC测量。与单独的临床风险评分相比，CAC评分比踝肱指数、hsCRP或颈动脉IMT更能提高对心血管风险的辨别能力。尤其是在糖尿病患者中，Budoff从他对成人糖尿病患者的研究中发现，CAC评分与总死亡率和心血管死亡率之间存在直接关系。他还指出了蛋白尿和NT-proBNP等生物标志物在评估2型糖尿病(T2D)风险方面的作用，强调影像在疾病预防中的重要性，而不是对于已经全面发展的疾病的治疗。

马里兰州巴尔的摩的Elizabeth Selvin讨论了肥胖和糖尿病与心力衰竭的关联问题，回顾了来自社区动脉粥样硬化风险(ARIC)研究的有力证据，该研究表明糖尿病病程与心力衰竭风险之间存在非线性关系，特别是在疾病开始后的前十年。她回顾了使用hs-cTnT的ARIC研究，这些研究可能反映慢性亚临床心肌损害。在无心血管病史的无症状者中，hs-cTnT≥14 ng/L与心力衰竭、总死亡率和冠心病的发病分别增加6倍、4倍和2.3倍相关。她的研究进一步表明糖尿病和糖尿病前期与hs-cTnT升高有关。这种关系受到肥胖的影响，体重指数和hs-cTnT与心力衰竭独立相关。此外，在对ARIC人群中9477人的17年随访中，与代谢健康的正常体重相比，肥胖与整体心血管疾病风险更高，尤其是心力衰竭风险更高。马里兰州巴尔的摩的Erin Michos回顾了来自动脉粥样硬化多种族研究(MESA)的数据，这些数据表明心力衰竭的发展与动脉粥样硬化心血管疾病和高脂血症的持续时间之间存在直接关系。类似地，随着肥胖持续时间的延长，心力衰竭的风险增加，每肥胖十年与hs-cTnT升高的可能性增加20%-30%相关，这提示了Michos所说的“肥胖对心肌的长期毒性效应”。

加利福尼亚州奥克兰的Erica Gunderson讨论了妊娠期糖尿病(GDM)、随后的糖耐量异常和CAC发展之间的相互关系。她指出，在美国，有10%-12%的女性患有妊娠期糖尿病，全世界有17%-20%的女性患有妊娠期糖尿病，其中20%-50%患有妊娠期糖尿病的女性会发展成T2D，有GDM病史的女性患CVD的风险增加1.7-3.0倍。她展示了最近发表的一项来自青年冠状动脉风险发展(CARDIA)研究的分析，在这项研究中，GDM女性在15-25年的随访中CAC的风险增加，即使没有后续的糖尿病，此外也与其他危险因素，如血脂异常、高血压和吸烟有关。Gunderson评论说，需要加强对GDM女性的随访，不仅是后续的糖尿病，还包括对其他心血管风险因素的干预。

纽约州的Andrea Dunaif讨论了多囊卵巢综合征(PCOS)，指出大约70%的PCOS妇女存在内脏肥胖的代谢风险表型，具有低HDL胆固醇。低密度脂蛋白胆固醇与高雄激素血症、胰岛素抵抗有关，糖尿病的可能性增加4倍，然而与体重无关，尽管50%-80%的PCOS妇女存在肥胖。PCOS是CVD的重要危险因素。人口筛查的一个有用问题是确定女性每年的月经是否少于6次，Dunaif指出，月经周期为40天或更长的人患糖尿病的几率增加2.18倍，发生心血管疾病的可能性增加1.53倍，尽管已发表的研究通常没有足够的研究时间跨度，使心血管疾病事件完全暴露。Michos进行了第二次演讲，阐述了性激素变化对心血管疾病和心力衰竭的影响，指出绝经后女性心血管疾病的增加是众所周知的，游离睾酮的升高与左心室质量增加、NT-proBNP水平升高、CAC进展以及冠心病和心力衰竭的可能性更大相关。绝经后妇女体内较低水平的脱氢表雄酮硫酸盐(DHEA-S)也与心脏病的发生有关，进一步加强了雄激素与心脏病关系的复杂性。相比之下，在男性中，DHEA-S和睾酮水平较低通常与更大的心血管疾病和心力衰竭风险相关，尽管服用睾酮可能会增加冠状动脉斑块体积，这导致美国食品和药物管理局(FDA)对使用睾酮的药物更加关注，因为可能会增加心血管事件风险。