Metabolic Cardiologist
The Heart of the Matter: How Metabolic Dysfunction Drives Cardiovascular Disease
Hypertension Hyperlipidemia & Heart Disease: Metabolic Disorders at the Core
Abstract summary
The article highlights the critical role of insulin resistance and metabolic dysfunction in the development of hypertension, hyperlipidemia, and heart disease. It argues that traditional approaches to treating cardiovascular disease often focus on managing symptoms rather than addressing the underlying root causes. The article emphasizes the importance of recognizing and addressing insulin resistance, which is a key predictor of cardiovascular disease. A holistic approach incorporating lifestyle modifications, stress reduction, and targeted interventions is proposed as a more effective way to manage cardiovascular disease and improve patient outcomes. By adopting this approach, healthcare providers can potentially prevent and reverse cardiovascular disease, reducing the burden of these conditions and improving overall heart health. Avoid ills and avoid pills.
Metabolic Cardiology
Hypertension, Hyperlipidemia, and Heart Disease are at the core of the most pressing health crises, claiming millions of lives worldwide. Despite their distinct manifestations, these conditions share a common root cause: metabolic dysfunction driven by insulin resistance and chronic inflammation. Traditional medical training has cardiologists and endocrinologists operating as separate islands, focusing on symptoms within their respective domains rather than exploring the interconnectedness of these conditions. Treating the downstream symptoms rather than addressing the root cause has become the norm. As a result, patients often receive piecemeal care, with treatment typically limited to medication and generic lifestyle advice like ‘watch your diet & lose weight’ , failing to address the complex interplay between metabolic and cardiovascular health.
The prevalence of these conditions is closely linked to Western lifestyle habits, including consuming highly processed foods & sugar, sedentary lifestyles, obesity, and chronic stress. The traditional approach to treating cardiovascular disease focuses on managing symptoms, treating the traditional risk factors of high blood pressure & high cholesterol but the emerging field of cardiometabolic medicine offers a new perspective, bridging the gap between cardiovascular care, metabolic health, and holistic approaches. This provides more effective care and improves both patient compliance and outcomes. By addressing the root causes of these conditions, we can work towards preventing and reversing the progression of cardiovascular disease, ultimately reducing the staggering number of deaths and dysfunction attributed to these conditions. We need to work towards a future where cardiovascular disease is no longer the leading cause of death with the focus towards health and well-being.
The link between insulin resistance and cardiometabolic disease is rooted in the complex interplay between metabolic and cardiovascular systems. Insulin resistance, often a precursor to type 2 diabetes, triggers a cascade of events that increase the risk of hypertension, hyperlipidemia, and heart disease. Western lifestyle has fueled the development of the Metabolic Syndrome, a cluster of symptoms describing the risks of developing diabetes, cardiovascular disease, stroke and heart attack. Insulin resistance is a consequence of the interplay between genetic predisposition and environmental factors; these include poor diet, excessive caloric intake, physical inactivity and chronic stress. These all contribute to the development of metabolic dysfunction and increase the risk of cardiometabolic disease.
Insulin tells the cell what to do with energy; to store it or burn it. Eating provides the body with the necessary fuel for survival. Dietary calories raise insulin and caloric restriction lowers insulin. With insulin resistance, insulin blood levels are chronically elevated while the body attempts to store excess energy into cells that have a decreased responsiveness to its effects. When insulin levels are high, energy is stored in the form of fat, reducing the breakdown of those fats and subsequently overall metabolism is reduced. Conversely, low insulin levels lead to the burning of fat and increases metabolism. Skeletal muscle is a large reservoir for circulating glucose, accounting for up to 70% of glucose disposal. Insulin resistance impairs muscle glucose uptake, redirecting glucose to the liver. This leads to increased liver triglyceride production, creating an environment of excess energy. As a result, lipids accumulate in and around abdominal organs, contributing to central obesity. The excess energy substrate has detrimental effects on the body, fueling metabolic dysfunction.
Let’s explore the relationship between metabolic dysfunction and cardiovascular disease. It is easy to measure cardiovascular disease but difficult to measure insulin resistance. Blood pressure, lipid levels and the presence of plaque in the arteries are concrete values. They all confer risk. Insulin resistance is difficult to measure and its value is more of a concept than a straightforward measurement. It’s a condition in which the body’s cells become less responsive to insulin and as a result the body produces more insulin to compensate. To put it simply, Insulin resistance develops when our fat cells become ‘too fat’, overloaded with excessive calories. Unlike common health metrics like blood pressure and cholesterol, many people are unaware of their insulin levels and even unaware that insulin levels can be measured. To complicate matters, insulin levels fluctuate depending upon food intake, stress and hormonal levels.
The gold standard for the evaluation of insulin resistance involves the Insulin Clamp Technique; infusing insulin and using radio-labeled glucose. Except for laboratory experiments this is never done. The closest thing to measuring insulin resistance in the clinical setting is in response to an oral glucose load called the oral glucose tolerance test - ‘OGGT’. After ingesting 75 grams of glucose, the serum glucose is measured fasting and at 1 hour intervals. This in conjunction with measuring insulin levels is very useful in assessing insulin resistance. This test is validated by the American Diabetes Association (ADA) to make the diagnosis of diabetes mellitus (glucose >140 is prediabetes, >200 is diabetes ). However this can be inaccurate for diagnosing insulin resistance and diabetes as it is commonly ‘normal’ in the early years of insulin resistance. Despite these factors, measuring sugar levels as a means of assessing insulin resistance in the form of either a fasting glucose or a Hemoglobin A1c is still frequently done. This is an erroneous practice; positive results are highly predictive but beware, elevated glucose levels are an extremely late manifestation of insulin resistance. Hence normal glucose doesn’t necessarily mean the absence of it. On average it takes about 10-20 years of insulin resistance and up to 85% failure of our pancreatic insulin producing cells to have even a ‘borderline’ elevated glucose, a condition referred to as prediabetes. Diabetes occurs with up to 90% of pancreatic burnout. Recent findings indicate that in high risk children, insulin resistance and diabetes is established by puberty due to obesity and sedentary lifestyles.
Other indicators of insulin resistance are the Triglycerides:HDL ratio (TG/HDL)- a value greater than 1.65-2.78 (more in men & less in females or certain ethnic groups) , a waist-to-height ratio (W:HtR) greater than 0.5 and clinically the presence of multiple skin tags, dark skin patches called acanthosis nigricans, PCOS or the presence of the features of the Metabolic Syndrome. Insulin resistance is silently fueling the fires of cardiovascular disease for many years prior to the development of sugar abnormalities and unfortunately this is ignored by many physicians.
The high prevalence of unknown diabetes mellitus (DM) in patients with coronary disease is well documented . The oral glucose tolerance test (OGTT) is the best diagnostic method in this context but unfortunately is rarely used. Clinical inertia replaces it with fasting glucose and Hemoglobin A1c, for the most part worthless when normal. As an example, the 2013 the American Journal of Cardiology published an article( Full-Text HTML ) looking at undiagnosed diabetes in heart disease. It evaluated patients with coronary artery disease but no “diabetes” as indicated by normal fasting glucose and a normal Hemoglobin A1c. The Oral Glucose Tolerance Test (OGTT) revealed that among those initially deemed nondiabetic, 44% actually had prediabetes or diabetes. Furthermore, when the remaining “nondiabetics” were followed for three more years, a staggering 82% developed abnormal test results, indicating a significant progression towards prediabetes or diabetes. In all, 90 % of those with cardiovascular disease and NO initial abnormal glucose values indeed had the ADA validated diagnosis of prediabetes/diabetes by 3 years. So significant yet so ignored. Insulin resistance is a stronger predictor of cardiovascular disease (CVD) compared to traditional risk factors like hypertension, high cholesterol, diabetes, obesity, and smoking. Yet these garner all the attention ! I have rarely seen a cardiologist measure or even assess insulin resistance as a risk factor for cardiovascular disease. Most deny its existence as it takes them out of their cardiology ‘comfort zone’ towards the abyss of metabolic dysfunction. This metabolic dysfunction unfortunately leads to a cluster of abnormalities that increase Cardiovascular Disease risk including blood vessel injury, inflammation, and atherosclerosis. https://doi.org10.1177/03000605231164548. Measuring insulin resistance can identify disease at its earliest stages, even with normal blood glucose and HbA1c levels, highlighting its importance in CVD risk assessment.
Insulin resistance contributes to HYPERTENSION through multiple mechanisms. It promotes absorption of sodium and water from the kidney, leading to volume expansion and increased blood pressure, as insulin's effect on sodium reabsorption in the kidneys remains active despite metabolic insulin resistance. It directly inhibits the production of nitrous oxide, a compound crucial for vascular relaxation and vasodilation, crucial in influencing blood flow & blood pressure aside from its anti inflammatory properties. Insulin resistance activates the sympathetic nervous system (the fight or flight part of the brain), increasing circulating adrenaline (catecholamines) contributing to hypertension. It promotes vascular smooth muscle cell growth and increases vascular reactivity, further elevating blood pressure. Normally, volume expansion would down-regulate renal insulin receptors, but this feedback mechanism may be defective in insulin-resistant states, perpetuating hypertension. Furthermore, insulin resistance is linked to chronic inflammation and oxidative stress, which also play a role in developing high blood pressure. These interconnected pathways highlight the complex relationship between insulin resistance and hypertension.
Insulin resistance significantly influences HYPERLIPIDEMIA as it disrupts normal lipid metabolism. Cholesterol is a normal component of all cells & hormones and when one has routine testing, they are given a total cholesterol number with breakdown of LDL, HDL & Triglycerides. However, certain subtypes of these are more significant in the production of atherosclerosis than others. Through complex pathways, insulin resistance results in increased levels of small, dense LDL particles and decreased HDL cholesterol. The characteristic lipid profile associated with insulin resistance includes high triglycerides, low HDL cholesterol, and an increased proportion of small, dense LDL particles, all of which contribute to an increased risk of cardiovascular disease. These are referred to as ‘Atherogenic Dyslipidemia’. This pattern is both predictive of the presence of insulin resistance and is one of the major drivers contributing to hardening of the arteries, thus increasing the risk of heart disease and stroke. With this pattern, an anatomical assessment of atherosclerosis such as a CT coronary calcium score would be beneficial in assessing the metabolic burden of disease, and if significant, a subsequent 2 hour OGTT with an insulin response. Only in this way can a personalized assessment and treatment plan be formulated matching the aggressive of the underlying pathology. Gone are the days of ‘watch your diet and take your Lipitor.’
Insulin resistance is at the core of HEART DISEASE. After an arterial wall injury, plaque develops in a sequence: inflammation, calcification, and ultimately, a necrotic core forms. Cholesterol is normally found in all cells including the cells making up the blood vessel walls. It doesn’t become deleterious until exposed to the proinflammatory effects of insulin resistance. This triggers an oxidation of the cholesterol with the production of free radicals , triggering an inflammatory response. This inflammation triggering atherosclerosis is marked by the accumulation of immune cells called macrophages. These cells engulf oxidized LDL cholesterol, transforming into "foam cells" due to their foamy appearance. This complex promotes further fat accumulation and due to its irritating nature, triggers a scarring response. The body attempts to isolate the area, called the fibrofatty plaque, by covering it with a fibrous cap and calcium , effectively burying the inflammatory complex. This has nothing to do with the calcium that you eat. This is akin to the Russians burying the Chernobyl nuclear plant disaster under 6 feet of concrete. By the time one has any calcification in their arteries (a CT calcium score of 1) it is already stage 5 atherosclerosis indicating an advanced and significant remodeling of the vessel wall.
Calcification appears to have little if any direct influence on the activity of the inflammatory vasculopathy as the underlying disease continues to progress. The real danger lies in the plaque's fibrofatty core, not the calcium layer. The fibrofatty core is like a volcano ready to erupt, while calcium acts as a containment wall. Notably, most heart attacks stem from plaque ruptures in vessels with less than 50% blockage, often undetected by standard stress tests, which typically identify stenosis above 70%. Not very reassuring. Tim Russert , the ‘Meet the Press’ journalist died from an acute heart attack 6 weeks after his normal stress test with a LDL<70. His plaque ruptured. CT imaging of his heart would have saved his life. Just as finding firefighters at a burning building doesn't mean they're causing the fire, discovering arterial calcium doesn't necessarily mean it's the primary cause of the problem. Instead, the calcium might be part of the body's response to inflammation, attempting to stabilize the arterial wall. While some studies suggest that coronary calcification can be slightly reversed, the key is stabilizing the plaque's core. The goal is to prevent the core from rupturing which can have serious consequences.
CT coronary calcium score, a rapid inexpensive test (averages $100) detects atherosclerosis early in its development by measuring the amount of calcium deposition in the vessel. A calcium score of 1 indicates that this process is advanced and the subsequent risk of an acute heart attack increases with elevated calcium scores. 1-10 low risk, 11-100 moderate risk, 101-400 moderate high risk and >400 high risk. For all essential purposes the amount of calcification reflects the magnitude, extent and severity of the injury caused by the inflammatory response in the vessel wall. However it does not reflect the current activity of that inflammation. I never understood why practitioners frequently waited until the plaque progressed to a higher risk category before instituting aggressive measures. I would personally prefer to put out the fire when it is a small flame rather than a large inferno. Early aggressive primary prevention of coronary artery disease can significantly reduce the risk of cardiovascular events, slow disease progression, and improve long-term outcomes.
By using intravenous contrast dye, the CTA coronary arteries can accurately measure the degree of that stenosis, its characteristics and the detection of noncalcified plaque which may be more prone to rupture. Calcification of the coronary arteries identifies the site and extent of atherosclerotic involvement. Calcification is a component not a complication of atherosclerosis.
Any stress on a vessel wall can cause inflammation including mechanical stress from an anatomical kink in a vessel or a junction between two vessels. This mechanical stress tends to cause a focal, segmental plaque, what I refer to as the ‘speed bump’. In contrast, insulin mediated inflammation causes a diffuse type of plaque across multiple areas of the vessel wall, what I refer to as the ‘cobblestone street’. I label this as the ‘ INFLAMMATORY VASCULOPATHY’. Metabolic processes affect the entire vessel. The higher the plaque burden, including corrected for your age & gender, the more likelihood the influence of metabolic effects from insulin resistance. All patients with evidence of diffuse inflammatory vascular disease should get a 2-hour glucose tolerance test, regardless of normal fasting blood sugar or normal hemoglobin A1C. I have coined the term ‘EUGLYCEMIC DIABETES MELLITUS’ to describe those patients that have a normal fasting blood sugar or hemoglobin A1C but have an abnormal 2-hour glucose tolerance test. The prefix "eu-" comes from Greek meaning "good" or "normal," indicating a state of normalcy or balance and in this case, of sugar. The cardiometabolic risk associated with insulin resistance isn't directly proportional to the severity of glucose abnormalities. Instead, it's a binary issue: insulin resistance is either present or it's not. Like pregnancy, there's no middle ground. Moreover, the degree of atherosclerosis doesn't correlate with the level of sugar elevation, suggesting that the presence of insulin resistance itself is the key factor. This is especially true in those patients with early onset or diffuse atherosclerosis as it’s the leading cause of atherogenic dyslipidemia and subsequent premature or rapidly progressive cardiovascular disease. Unfortunately, many patients are told not to worry about low calcium scores or non obstructive blockages and are put on statin medications as “prevention “. CT imaging has demonstrated that despite using high dose statin therapy, in as little as 18 months the fibrofatty plaque will continue to grow by 32%. In contrast, the addition of an anti-inflammatory omega 3 fatty acid (icosapent ethyl) shrinks that same plaque by 34% over the same time period. (European Heart Journal-EVAPORATE trial https://doi.org/10.1093/eurheartj/ehaa652 ) Yet the lack of recognition of insulin resistance and the effects of inflammation on the blood vessel wall frequently prompts the reflex response of prescribing statins and nothing more. Approximately 75% of heart attack sufferers do not have dangerously high LDL (bad) cholesterol levels. While high LDL is a risk factor, these other factors contribute significantly to heart attacks, and a significant portion of heart attacks occur in people with "normal" cholesterol.
HEART FAILURE constitutes a substantial portion of the overall cardiovascular disease burden, contributing significantly to morbidity, mortality, and healthcare costs. Heart failure is characterized by either pump failure -HFrEF or in the impairment of the relaxation phase of the heart despite a normal wall motion - HFpEF. Heart failure with a preserved ejection fraction is usually the result of a stiff heart, unable to relax and fill but is pumping normally. Both of these are highly correlated with insulin resistance and diabetes, even in the absence of obstructive coronary artery disease. Insulin resistance is a significant predictor of heart failure promoting inflammation, oxidative stress, and metabolic dysregulation. This damages cardiovascular tissues and increase heart failure contributing to cardiac dysfunction. In HFpEF, metabolic dysregulation and inflammation exacerbate diastolic dysfunction( heart relaxation), while in HFrEF, impaired energy metabolism and increased oxidative stress worsen systolic dysfunction( heart contraction). The major pharmacological advances in heart failure treatment have all revolved around drugs originally used for diabetes. Addressing insulin resistance through lifestyle modifications and recognizing insulin resistance early in the development of heart disease can help mitigate its impact on heart failure outcomes and improve cardiovascular health.
Holistic approaches can positively impact HYPERTENSION , HYPERLIPIDEMIA AND HEART DISEASE by addressing underlying factors. A balanced diet rich in whole foods, fruits, and vegetables can help lower blood pressure and cholesterol levels. Supplements with essential vitamins and minerals are crucial in maintaining metabolic balance. Regular exercise, ideal lean body weight and stress reduction techniques such as meditation & yoga can also contribute to improved cardiovascular health. Additionally, omega-3 fatty acids and antioxidants found in certain foods and supplements may help reduce inflammation and improve heart function. By incorporating these natural strategies, individuals can potentially reduce their risk of cardiovascular disease and improve overall heart health.
The intricate relationship between metabolic dysfunction and cardiovascular disease underscores the pivotal role of insulin resistance in hypertension, hyperlipidemia, and heart disease. Cardiologists must broaden their perspective beyond cholesterol-centric approaches and acknowledge the metabolic drivers underlying most cardiovascular conditions. By recognizing and addressing insulin resistance, healthcare providers can develop more effective treatment strategies, reducing the burden of these conditions. By adopting a holistic approach incorporating lifestyle modifications, stress reduction, and targeted interventions, we can work towards preventing and reversing cardiovascular disease. Ultimately, this shift in focus can help create a world where individuals thrive, free from preventable disease, and cardiovascular disease is no longer the leading cause of death.
I dedicate this article to my good friends who were diagnosed with significant heart disease at a young age and given statins without any metabolic assessments by their cardiologists.
To Jim M. , Mike V.-the Olympian, Johnny C., Vinny M., Donna M. and Richie A. Upon further assessment all had metabolic issues of insulin resistance as core drivers of their atherosclerosis. Hopefully this will inspire future generations of physicians to look beyond just treating symptoms and instead focus on addressing the underlying metabolic issues driving cardiovascular disease. By doing so, they can provide more comprehensive, individualized care and help patients achieve better outcomes. It’s a matter of Life or Death.
Author: John C. Sciales M.D.
Director CardioCore Metabolic Wellness Center
