Gender Matters: Cardiovascular Disease Risk in Women and How to Manage – Part 2

This is a summary of a presentation on women and cardiovascular disease hosted by the Federation of Medical Women of Canada Ottawa Branch on January 10, 2019 as part of their Evening Dinner & Lecture Series. Part 1 on Cardiovascular Risk in Pregnancy can be found here. A summary of both talks appeared in The Medical Post, January 31, 2019. Gender differences in cardiovascular he...nadian Healthcare Network - Physicians

Women and Diabetes

Dr. Amel Arnaout, MD, FRCPC
Program Director, Division of Endocrinology and Metabolism Residency Training Program
Assistant Professor, Department of Medicine
University of Ottawa 

Roughly 3.4 million Canadians, or 9.3% of the Canadian population, are affected by Diabetes Mellitus (DM). Though this chronic disease has the same name in men and women, and certainly shares common risk factors, pathological mechanisms, complications, diagnostic methods, and management principles, there are important differences between men and women when it comes to DM. In her presentation, Dr. Arnaout took the opportunity to address some of these similarities and differences, and to advocate for the undeniable truth - gender does matter.

Epidemiology & Risk Factors

Obesity increases the risk of developing pre-DM as well as DM. Men however tend to present with DM at younger ages and with lower BMIs compared to women, therefore suggesting that obesity in men may not be quite as significant a risk factor as it is in women. This could be due to a number of reasons. One relates to body fat distribution, where women are known to carry more visceral (high-risk) fat and men more subcutaneous (low-risk) fat. Another relates to brown adipose tissue, which is known to be more metabolically active and therefore protective, is found in higher quantities in men compared to women. In addition to obesity, the development of DM is more closely tied to income-based socioeconomic status in women. In Canada, it is women and not men with lower household income and food insecurity who have a have a higher DM risk.

From a biological perspective, there are known sex-specific factors that can lead to the development of DM. The sex hormones estrogen and testosterone, and the balance of the two, are known to play a role, as demonstrated in women with conditions related to sex hormone imbalance/androgen excess (i.e. Polycystic Ovarian Syndrome and Pre-Mature Menopause) and men with androgen deficiency. Clearly distinctive are also pregnancy-associated conditions – specifically Gestational DM (GDM), Hypertensive Disorders of Pregnancy (HDP), and Pre-Term Labour – which of course can only manifest in females. Women who develop these conditions have a higher risk of developing DM in the future, and their children have a higher lifetime risk of DM as well, particularly if they are born at low and/or high birth weights.

Complications

In both men and women with DM, macrovascular disease is the leading cause of death. However, such disease tends to be more severe and/or prevalent in women. For example, compared to individuals without DM, the risk of Coronary Artery Disease (CAD) increases 2- to 5-fold in women with DM, whereas it only increases 1- to 3-fold in men with DM. There is also a greater risk of CAD-related mortality in women versus men with DM. The traditionally recognized “protective effect” of female gender therefore appears to be lost in females with DM. Potential reasons for this include higher rates of additional risk factors obesity, dyslipidemia, and hypertension in women with DM, with contributions from female-specific conditions related to sex hormone imbalance which are often associated with higher CAD risk (i.e. Polycystic Ovarian Syndrome and Pre-Mature Menopause).

Screening & Diagnosis

When it comes to screening, there are currently no differences in the recommendations between women and men. Current guidelines recommend screening for DM every three years starting at 40 years old, or earlier if known risk factors and/or symptoms. Standard screening in both genders entails checking fasting glucose and glycated hemoglobin (Hemoglobin A1c or HbA1c), then jumping to the 2-hour Oral Glucose Tolerance Test (OGTT) if any borderline results. However, Dr. Arnaout notes that there are important differences in glucose metabolism between men and women that should be accounted for when it comes to screening. When given a 2-hour OGTT, women demonstrate lower fasting glucose levels and higher 2-hour glucose levels compared to men. This means that the standard method of screening, which starts with fasting glucose, may actually be inadequate in women. Furthermore, HbA1c tests can be confounded by conditions such as anemia, which is very common in menstruating women. Dr. Arnaout therefore advocates instead for high risk women to be screened initially with a 2-hour OGTT and HbA1c to reduce the risk that they’ll slip through the cracks. She further advocates for screening to be performed annually in women with previous gestational DM for the rest of their lives, as they are at a higher risk for developing DM in the future. The traditional 3-year screening interval is a long time to go without adequate detection and therapy.

Management

Current guidelines make a wonderful recommendation for DM therapy – individualization. While factors such as patient age, duration of disease, complications of disease, and hypoglycemia are often clearly accounted for, gender is not. Once again, Dr. Arnaout advocates for this to change. Women are known to have higher rates of depression and/or anxiety, and are less likely to engage in active problem-solving approaches compared to men. Women also respond more than men to external sources of support, displaying higher rates of attendance at formal education programs. Finally, interventions specifically aimed at weight loss are proven to yield greater benefit in women versus men when it comes to clinical and psychological parameters. Taken altogether, Dr. Arnaout therefore recommends referring and encouraging women to attend educational DM workshops, and to focus on treatment methods that promote weight loss for optimal management of DM in women.

While dietary changes, exercise and other lifestyle modifications are important and essential components of DM management that can promote weight loss and should always be emphasized, certain medications are particularly well-suited to weight loss and women. Metformin, for example, is a safe and often first-line medication used. It is known to have cardiovascular benefits, promote ovulation induction in women with PCOS, and lower the risk of breast and colorectal cancer. Glucagon-Like Peptide-1 Agonists (i.e. Liraglutide, Exenatide, Lixisenatide) are also known to have cardiovascular benefits in high-risk patients and promote weight loss. SGLT-2 Inhibitors (“-flozins”) are used commonly in high-risk patients and work by promoting glucose loss through the urine. They, too, promote weight loss and have demonstrated cardiovascular benefits in this population. However, due to the glucosuria they induce, SGLT-2 Inhibitors do place women at a higher risk of Urinary Tract Infection (UTI), vulvovaginitis, and other genital infections, as well as Diabetic Ketoacidosis (DKA). That said, these risks tend to improve over the course of treatment once glucose levels improve.

As with starting any medication, says Dr. Arnaout, the key is to start low and go slow. This promotes patient safety, avoids side effect profiles, and yields more pleasant treatment experiences overall, thereby ensuring continuity and compliance with therapy long-term.

Summary

Roughly 3.4 million Canadians, or 9.3% of the Canadian population, are affected by Diabetes Mellitus (DM). Though this chronic disease has the same name in men and women, and certainly shares common risk factors, pathological mechanisms, complications, diagnostic methods, management principles, and treatments in both genders, there are important differences between men and women when it comes to DM. In her presentation, Dr. Arnaout takes the opportunity to address some of these similarities and differences, and to advocate for the undeniable truth - gender does matter.

Epidemiology & Risk Factors
🔹Obesity, particularly visceral obesity, increases the risk of developing pre-DM as well as DM
As women have higher obesity rates than men and tend to have more visceral fat, women with obesity may be more at risk of developing DM compared to their male counterparts

🔹The development of DM is more closely tied to income-based socioeconomic status in women
In Canada, it is women and not men with lower household income and food insecurity who have a have a higher DM risk

🔹Gestational DM (GDM) is a strong independent risk factor for the future development of DM in both a mother and her baby

Screening
🔹Women demonstrate lower fasting glucose levels and higher 2-hour glucose levels compared to men, and if menstruating are more prone to anemia which can interfere with HbA1c levels
This means that the standard method of screening, which often starts with fasting glucose and HbA1c levels, may actually be inadequate in women

🔹To screen high risk women for DM, start with a 2-hour Oral Glucose Tolerance Test (OGTT) and HbA1c to reduce the risk that they’ll slip through the cracks

🔹Due to their risk of developing DM in the future, women with GDM should be counselled appropriately and screened for DM annually for the rest of their lives to avoid delayed diagnosis and therapy

Complications
🔹A diagnosis of DM negates the relative cardiovascular protection a woman is provided

🔹While macrovascular disease is the leading cause of death in both men and women with DM, women with DM are more likely to develop Coronary Artery Disease (CAD) compared to men
 Compared to individuals without DM, the risk of CAD increases 2- to 5-fold in women, whereas it only increases 1- to 3-fold in men

🔹There is also a greater risk of CAD-related mortality in women versus men with DM

Management
🔹Particularly aggressive cardiovascular risk factor management is warranted in women with DM

🔹As women respond more than men to external sources of support and display higher rates of attendance, providing DM education through formal counselling sessions is encouraged

🔹Interventions specifically aimed at weight loss are proven to yield greater benefits in women versus men when it comes to clinical HbA1c and psychiatric parameters
Weight loss through dietary changes, exercise, and other lifestyle modifications should therefore be strongly encourage

Preference should be given to medications known to be cardioprotective and weight-loss inducing for optimal management of DM in women – Metformin, Glucagon-Like Peptide-1 Agonists, and SGLT-2 Inhibitors are all known agents

Thank you to University of Ottawa, MD students, Julie Lombardi and Sara-Michelle Gratton who provided the summaries of both talks at the January 10th event.

Thank you to all who came! What an enlightening evening about an important subject for women’s health.

Don’t forget to check out the events on the Wear Red Canada Campaign to raise awareness around women’s heart health. Find out more here: https://cwhhc.ottawaheart.ca/how-get-involved/wear-red-campaign

 

Dr. Bev Johnson
Chair, Gender Equity and Diversity Committee
President, Ottawa Branch

 

 

 

 

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