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Cardiovascular disease is the number one cause of death among women in the United States. (CDC 2024) However, 64% of women who die of sudden cardiac disease don’t experience any symptoms before their death. (Florida Heart Research Foundation n.d.) Keep reading to learn more about how a few common medical conditions have a surprising impact on cardiometabolic health status in women.

The role of inflammation in cardiometabolic health

Inflammation plays a critical role in our body's defense mechanism and healing process. (Chen 2018) However, when inflammation persists, it leads to continuous activation of immune cells, releasing inflammatory cytokines and chemokines, which attract even more immune cells. This ongoing response can alter the structure of various tissues, including blood vessels, and contribute to oxidative stress. (Furman 2019)

Chronic inflammation has a major impact on lipoproteins. While lipoproteins like low-density lipoprotein (LDL) and high-density lipoprotein (HDL) are crucial for our health and immune function, they can become harmful when oxidized. Oxidized LDL, for example, can damage the vascular system and contribute to the formation of unstable plaques in the arteries. (Nooti 2023)

Unstable plaques are highly concerning, as they're more prone to rupture, which can lead to serious cardiovascular events like myocardial infarction (heart attack), stroke, and unstable angina. (Nooti 2023) Plaque rupture can occur from both inside and outside the artery. Internally, chronic inflammation can weaken plaques, making them more likely to break. Externally, endothelial dysfunction—when the inner lining of blood vessels fails to function properly—can also lead to plaque rupture. (Loftus 2011)

Even minor plaque ruptures can exacerbate the inflammatory process. They attract more inflammatory T cells, like TH1 cells, which produce additional pro-inflammatory cytokines and enzymes such as metalloproteinases. These enzymes remodel arterial tissues, potentially thinning the plaque walls and making them even more susceptible to future ruptures. (Napiórkowska-Baran 2023)

Chronic conditions linked to cardiovascular health

Inflammation is a common link between all of the following conditions, emphasizing their role in cardiovascular disease.

Hyperthyroidism

Hyperthyroidism is closely linked to heart problems, particularly rhythm problems. It can cause atrial fibrillation, tachycardia, palpitations, and hypertension. Even subclinical hyperthyroidism can have these effects, making it important to check a patient’s thyroid levels when they display symptoms of tachycardia or develop unexplained atrial fibrillation or hypertension. (Ahmad 2022)

When testing for hyperthyroidism, guidelines recommend starting with a screening for TSH levels. However, a more comprehensive screening including free T4 and free T3 along with autoimmune markers—specifically thyroid-stimulating immunoglobulin test (TSI)—can help verify the presence of autoimmune hyperthyroidism.

Hypothyroidism

Up to 7% of Americans have overt hypothyroidism, with the majority of those being women. Overt signs of hypothyroidism include fatigue, weight gain, cold intolerance, constipation, dry skin, and brain fog. (Chaker 2017) However, there are also less obvious signs of hypothyroidism, which can still impact the cardiovascular system, making it crucial to be vigilant for subclinical hypothyroidism in patients as well.

Thyroid hormone plays a critical role in heart muscle function. Cardiac contractility, which is the ability of the heart to contract and pump blood, is closely related to thyroid levels. (Yamakawa 2021) In fact, people in intensive care units with heart failure and low T3 levels have a much higher mortality rate, highlighting the importance of thyroid hormones in myocardial health and function. (Gutch 2018)

Thyroid hormones are also involved in vascular function, affecting blood pressure and arrhythmias. Additionally, low thyroid levels can lead to elevated cholesterol levels, specifically LDL and total cholesterol. (Chaker 2017) If a patient has high cholesterol but is eating well and exercising, consider testing for hypothyroidism.

When testing for hypothyroidism, it’s essential not to rely solely on thyroid-stimulating hormone (TSH) levels. A comprehensive panel including free T4 and free T3 levels, along with autoimmune markers thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) can better help identify low thyroid function. (Pirahanchi 2023) (Vargas-Uricoechea 2023) For more detailed information, be sure to review the hypothyroid lab assessments guide.

Hypothyroidism is associated with an increased cardiovascular risk. Regularly assess lipids, and monitor triglyceride levels in particular, as they are often elevated in hypothyroid patients. (Mavromati 2021) Regularly checking the carotid intima-media thickness (CIMT) in patients with other cardiovascular risk factors is suggested as well. (Naqvi 2014)

Women with hypothyroidism also have a high rate of diastolic dysfunction, where the heart becomes stiffer and less energetic, not relaxing well during the diastolic phase. (Kim 2021) This condition is sometimes overlooked by cardiologists, but it's important to get an echocardiogram if there's any doubt. Additionally, heart rate variability is a crucial marker of health, so make sure to consider this in your evaluations. (Mccraty 2015)

Key inflammatory markers to monitor

When managing patients with hypothyroidism, especially those at risk for cardiovascular issues, monitoring inflammation markers is crucial. Helpful inflammation monitoring tests include:

• Asymmetric dimethylarginine (ADMA): ADMA is an indirect measurement of nitric oxide levels and inflammation. (Ragina 2017)

• F2-Isoprostanes: These measure lipid peroxides, indicating oxidative stress and lipid peroxidation. Elevated levels are often associated with poor diet and increased cardiovascular risk. (Davies 2011)

• High-sensitivity C-reactive protein (hs-CRP): Elevated hs-CRP levels are associated with inflammation and an increased risk of heart disease. (Carrero 2019)

• Lp-PLA2 activity: This enzyme is linked to plaque instability, providing insight into the vulnerability of arterial plaque. (Steen 2013)

• Microalbumin: This test measures the amount of protein in urine. Elevated levels, not related to kidney disease, indicate leaky arteries, a sign of endothelial dysfunction. (Koroshi 2017)

• Myeloperoxidase (MPO): This enzyme is involved in the core of plaque within the arteries. Elevated levels indicate plaque instability, suggesting a higher risk of cardiovascular events. (Teng 2016)

• Oxidized LDL: Unlike regular LDL, oxidized LDL is a marker of metabolic syndrome and oxidative stress, both of which are significant risk factors for cardiovascular diseases. (Manzoor 2022)

80% of autoimmune diseases occur in women, which is especially concerning due to the role these conditions play in cardiovascular health. (Angum 2020)

Autoimmune diseases

80% of autoimmune diseases occur in women, which is especially concerning due to the role these conditions play in cardiovascular health. (Angum 2020)

Key inflammatory markers to monitor

Monitoring specific inflammatory markers in women with autoimmune diseases can provide critical insights into cardiovascular health risks:

• hs-CRP: This is a surrogate marker for inflammatory cytokines like interleukin-6 and tumor necrosis factor-alpha. Chronically high hs-CRP levels, often over 10, indicate a significant risk factor. (Province of British Columbia 2023)

• Rheumatic disease indicators: Autoimmune diseases often involve joints, but they can also affect the skin, eyes, lungs, kidneys, heart, and vascular system. Rheumatoid arthritis (RA), the most common rheumatic disease, has a well-documented relationship with heart disease. Women with severe RA have high levels of inflammatory markers and are at significant cardiovascular risk. (Popescu 2023)

Cardiovascular screening

One study showed that only 55% of women with RA had their lipids measured, and those under the care of rheumatologists were even less likely to receive cardiac screenings. Angina is often misdiagnosed in these patients, assumed to be musculoskeletal rather than cardiac in nature. (Crowson 2013)

Women with RA have an increased chance of developing cardiovascular disease and in severe cases are more likely to have had a myocardial infarction. (Farhat 2022) They are also at increased risk for venous thromboembolism and heart failure. (Mansour 2019) Systemic inflammation from RA can lead to diastolic dysfunction, indicating an energy deficiency in the heart. (Chen 2021)

Understanding lipid profiles

In autoimmune diseases, lipid profiles can be paradoxical. Women with RA often have lower levels of LDL and HDL cholesterol, which can be misleading as lower cholesterol is typically perceived as a lower cardiovascular risk. However, in these patients, low cholesterol levels often correlate with more severe systemic inflammation and increased cardiovascular events. (Myasoedova 2011)

Therefore, it's crucial not to rely solely on lipid profiles but to include comprehensive inflammatory markers to assess cardiovascular risk accurately. Tests such as advanced lipid profiles, including particle fractionation testing, ApoA1, and ApoB, help provide a clearer picture of cardiovascular health.

Additional diagnostic considerations

For a comprehensive assessment, consider the following tests for patients with autoimmune diseases:

• Advanced lipid profiles: Including assessment of lipoprotein subclasses (also called NMR lipid testing), along with markers such as ApoA1 and ApoB levels

• Antinuclear antibody (ANA) panel: To screen for lupus, Sjögren’s syndrome, and scleroderma

• Genetic markers like ApoE: Associated with detoxification efficiency and increased cardiovascular risk (Alagarsamy 2022)

• Homocysteine, B12, and folate levels: Important for assessing overall health and cardiovascular risk

• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP): To check for rheumatoid arthritis

• Trimethylamine N-oxide (TMAO): The primary gut marker for cardiovascular risk, linking gut microbiome dysbiosis with heart health (Rahman 2022)

• Uric acid levels: Elevated levels are a marker for cardiovascular risk (Shahin 2021)

Osteoarthritis

According to the World Health Organization, 60% of the people living with osteoarthritis are women. (WHO 2023) However, the link between osteoarthritis and cardiovascular disease has gone largely unrecognized.

When assessing patients for osteoarthritis, it’s important to consider:

• Bone health: Bone health plays a crucial role in osteoarthritis, and it’s essential to understanding its implications for cardiovascular disease. (Wei 2023)

• Estrogen: Estrogen is vital for maintaining musculoskeletal structures, including cartilage, bone, tendons, and muscles. Estrogen deficiency states can lead to an increase in musculoskeletal problems, including osteoarthritis. (Roman-Blas 2009)

• Ferritin levels: High ferritin levels can indicate cardiovascular risk. (Guo 2022) Ferritin, a carrier protein for iron produced in the liver, can be elevated due to liver inflammation, such as fatty liver. Patients with elevated ferritin levels and liver enzymes should be screened for fatty liver using an ultrasound.

• Rheumatoid arthritis: It's possible for patients to have both osteoarthritis and rheumatoid arthritis. Postmenopausal women, in particular, are at increased risk for both conditions due to the loss of estrogen. (Talsania 2017) It’s important to assess for and rule out RA in testing for osteoarthritis.

Other labs

When managing osteoarthritis patients, consider the following labs to assess cardiovascular risk and help rule out other conditions:

• Autoimmune disease markers: It's essential to rule out conditions like lupus, which can affect the joints and coexist with osteoarthritis.

• Ferritin: High levels can indicate liver inflammation and cardiovascular risk. (Guo 2022)

• Liver enzymes: Elevated levels can point to liver issues, including fatty liver.

Osteoporosis

While the relationship between cardiovascular disease and osteoporosis is often overlooked, research has demonstrated that low bone mineral density is closely linked to an increased risk of cardiovascular mortality and morbidity. (Farhat 2008)

There's also a link between the calcification processes in bones and arteries. Osteoclasts, which are modified macrophages, play a role in bone resorption. In an inflammatory state, these cells can lead to both bone demineralization and arterial calcification. (Cannata-Andia 2011)

Additionally, osteoporosis is an active inflammatory process. The OPG/RANK/RANKL triad, which regulates bone remodeling, becomes dysregulated in inflammatory states. (Glasnović 2020) High levels of inflammation contribute to both osteoporosis and cardiovascular diseases.

Key lab tests

To comprehensively evaluate patients with osteoporosis, consider the following lab tests:

• Autoimmune screening: In young women with unexplained fractures, consider testing for celiac disease and gluten autoimmunity, as malabsorption issues can impact bone health. (Katz 2010)

• Inflammatory markers: Elevated inflammation is linked to osteoporosis and cardiovascular disease. Measuring certain markers including advanced lipid profiles and homocysteine levels is helpful.

• Nitric oxide surrogate markers: These assess the balance of nitric oxide production, which influences both vascular health and bone remodeling.

• Parathyroid hormone: This can rule out hyperparathyroidism, which can contribute to bone loss.

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women; however, it’s also a major risk factor for cardiovascular and metabolic problems. Women with PCOS may exhibit high levels of inflammation. (Orisaka 2023)

Endometriosis

10% of women have endometriosis, but its strong cardiovascular risk relationship is often overlooked. (WHO 2023) Research has found that women with endometriosis experience both chronic systemic inflammation as well as local pelvic inflammation. (Taylor 2021) Key findings in women with endometriosis include:

• Decreased antioxidants: Lower levels of antioxidants in the peritoneal fluid and peripheral blood

• Increased oxidative stress: Elevated markers of oxidative stress in both the peritoneal fluid and peripheral blood

• Heightened inflammatory factors: Increased inflammatory markers in the peritoneal fluid and peripheral blood (Scutiero 2017)

Female reproductive health plays an important role in cardiovascular health. 

Uterine fibroids

Studies have revealed that women with uterine fibroids are more likely to be metabolically unhealthy and have a higher risk of cardiovascular issues, including obesity, hypertension, lipid abnormalities, and increased carotid intima-media thickness. (Brewster 2022)

Lab testing

For women with reproductive issues, including fibroids, it's essential to conduct comprehensive lab tests. This includes testing for heavy metals and phthalates, which have been linked to cardiovascular disease as well as fibroids. (Mariana 2020) The evidence links environmental toxins to both cardiovascular disease and uterine fibroids through mechanisms involving endocrine disruption, oxidative stress, and inflammation. (AlAshqar 2023) (Ye 2017) Arsenic, lead, and mercury in addition to phthalates are associated with hypertension and cardiovascular events. (Yang 2020) Cadmium and phthalates have been associated with an increased risk of developing uterine fibroids. (Northwestern University 2022)

Vaginitis

Research shows a connection between vaginitis and cardiovascular health. Women with recurrent vulvovaginitis often have higher BMIs and are more likely to be obese, suggesting a potential link to cardiovascular issues. (Brookheart 2019) Although research is still in its early stages, it's essential to consider that women with recurrent vaginal infections may also have an increased risk for cardiovascular disease.

Lab testing

When addressing chronic vaginitis, it's crucial to go beyond the usual pathogens like Trichomonas, Candida, and Gardnerella. Modern diagnostic methods allow the use of polymerase chain reaction (PCR) to detect DNA from mycoplasma and ureaplasma—major infectious agents that often go untreated and unrecognized because they don't show up in standard cultures.

Different strains of Lactobacillus also play a role in vaginitis. For instance, Lactobacillus iners is associated with a worse prognosis for vaginitis. (Zheng 2019) This emerging area of research highlights the need for a broader approach to diagnosing and treating chronic vaginitis.

Given the potential link between vaginitis and cardiovascular risk, it's important to include comprehensive testing for women with chronic vaginal infections. This includes:

• Human papillomavirus (HPV) screening: Check for HPV, which can contribute to reproductive health issues.

• Lipid profile: Assess all lipid levels to understand the patient's metabolic health.

• Inflammatory markers: Evaluate inflammatory markers to identify any systemic inflammation that might be present.

An integrative approach to cardiovascular risk

While some factors, such as age, sex, and race, are beyond our control, many lifestyle factors can be influenced to improve patient cardiovascular health.

Diet

Following the Mediterranean diet may be helpful in supporting cardiovascular health. Emphasize a diet rich in polyphenols, vegetables, fruits, whole grains, and healthy fats. (American Heart Association 2024)

Encourage the consumption of fermented foods and probiotics to enhance gut health, which plays a significant role in overall cardiovascular well-being. (Leeuwendaal 2022) Additionally, recommend unprocessed carbohydrates like whole grains to help grow a healthy microbiome.

Exercise

Encourage a routine exercise program tailored to each patient’s needs. Exercise improves the gut microbiome, supports cardiovascular health, and can reverse impaired microvascular nitric oxide function in sedentary adults. (Nystoriak 2018) Conduct body composition analyses and fitness assessments to better understand and track patient progress.

Hormone balance

Proper hormone regulation is vital. Monitoring and managing thyroid hormones, adrenal hormones, and sex hormones can prevent cardiovascular issues.

Intermittent fasting

Consider implementing intermittent fasting or a fasting-mimicking diet to reduce inflammation and cardiovascular risk. (Malinowski 2019)

Sleep and stress management

Adequate sleep and effective stress management are crucial for maintaining cardiovascular health. (American Heart Association 2024) (American Heart Association 2024)

Assessing chronic medical conditions to support cardiometabolic health

While often overlooked, the common link between all of these chronic medical conditions is inflammation. Understanding the role of inflammation in the development of cardiometabolic diseases is the best way healthcare practitioners can detect these cases early and support their patients’ best health outcomes.