Cardiovascular Disease & Preventative Measures

Introduction

Luci Fontana, the Ulman chair in Transitional Metabolic Health, discusses nutrition and exercise in preventing aging and chronic diseases, focusing on cardiovascular disease (CVD) due to its prevalence as a leading cause of mortality and morbidity.

The Complexity of Mortality

Mortality is rarely due to a single cause; in Australia, approximately 23.9% of deaths involve five or more contributing factors, and nearly 60% involve at least three.

  • Comorbidity: The number of conditions increases with age. Approximately 80% of individuals aged 65-85 have at least one chronic disease, and 65% have two or more.

  • Shared Metabolic Substrate: Many common chronic diseases share a metabolic basis.

Current Medical Approach vs. Lifestyle Intervention

The current medical model often treats diseases in a specialized manner (e.g., prostate cancer, heart failure). However, many common conditions, including CVD, vascular dementia, common cancers, fatty liver disease, and diabetic/hypertensive nephropathy, share a common metabolic substrate. Lifestyle factors heavily influence this cardiometabolic risk profile. Modifying these factors can prevent multiple diseases simultaneously, contrasting with the current system of treating diseases as they manifest clinically.

  • Central Adiposity: Abdominal obesity is a key factor. It leads to insulin resistance, inflammation, prediabetes, diabetes, hyperinsulinemia, and alterations in growth factors linked to cancer.

  • Statistics: High rates of overweight and obesity are observed across all age groups in Australia with almost 90% of men and women aged 65-74 exhibiting waist circumferences indicating increased metabolic risk.

  • Type 2 Diabetes: This condition is strongly correlated with excessive central adiposity. Its prevalence has significantly increased, reaching approximately 18% in the 70-84 age group as of February 2022.

  • Fatty Liver Disease: Fatty liver disease affects approximately 40% of Australians.

Atherosclerotic Cardiovascular Disease

The primary cause of CVD in Western countries is atherosclerotic cardiovascular disease. Myocardial infarction, stroke, heart failure, peripheral arterial disease, and vascular dementia are all strongly linked to atherosclerosis.
Atherosclerosis is an inflammatory condition driven by dyslipidemia, hypertension, diabetes, and other factors.

Cardiometabolic Risk Factors

  • Non-modifiable: Age, genetics, family history

  • Modifiable: Smoking, high blood pressure, diabetes, elevated LDL cholesterol, elevated triglyceride-rich lipoproteins, and low HDL cholesterol are major risk factors.

  • Approximately 20% of coronary heart disease cases occur in people with normal classical risk factors.

Preventability

The World Health Organization estimates that at least 80% of heart disease, stroke, and type 2 diabetes, and over 40% of cancer cases are preventable through healthy lifestyles.

  • Tsimane Tribe Study: A Lancet study comparing the Tsimane people of the Bolivian Amazon with individuals in the U.S. showed significantly lower rates of cardiovascular disease among the Tsimane, indicating that atherosclerotic CVD is not inevitable and is strongly influenced by lifestyle.

  • For people aged 75-84, only 8% of the Tsimane had a calcium score higher than 100, compared to 51% of people in the U.S.

American Heart Association Guidelines (2021)

The American Heart Association (AHA) guidelines are used as a reference point for discussing how lifestyle interventions influence cardiovascular disease, providing evidence-based recommendations.

  • 10 Points in the AHA Guidelines:

  1. Adjust energy intake and expenditure to achieve and maintain a healthy body weight.

  2. Eat plenty of fruits and vegetables.

  3. Choose foods made mostly with whole grains rather than refined grains.

Guideline 1: Healthy Body Weight

Reduce waistline while preserving or increasing skeletal muscle mass. Big muscles are important for glucose metabolism.

  • Even within a normal BMI range (21-23), higher waist circumference correlates with increased diabetes risk, emphasizing that fat location matters.

  • Study at Washington University:

    • Men and women aged 50-60 with a BMI of 25-30 were randomized into three groups: control, exercise (25% increase in energy expenditure), and calorie restriction (25% reduction in caloric intake).

    • After one year, both exercise and calorie restriction groups achieved approximately 8% weight loss.

    • The exercise group engaged in one hour of exercise six days a week at 72-80% of their maximum heart rate.

    • Daily routine is essential for metabolic benefits from exercise, similar to daily medication.

    • Both groups experienced an almost 40% reduction in visceral fat. One participant lost 16 kg (14% of body weight) through exercise alone, resulting in a 74% reduction in visceral fat.

    • There was a significant improvement in glucose tolerance and insulin sensitivity, based on OGTT (oral glucose tolerance test) measurements.

    • Visceral fat produces hormones (adipokines) that block insulin action, causing insulin resistance and compensatory hyperinsulinemia.

    • Insulin Resistance: Even before glucose levels rise, insulin resistance results in increased insulin production postprandially. This is especially relevant given the constant availability of food.

    • The insulin/IGF-1/mTOR pathway is a critical pro-aging, pro-cancer pathway. Overstimulation accelerates the risk of chronic diseases by downregulating autophagy, DNA repair, and endogenous antioxidant pathways while stimulating proliferation.

    • Exercise vs. Calorie Restriction: Exercise is more potent than calorie restriction for improving insulin sensitivity, because it reduces visceral fat. Exercise increases GLUT4 production and translocation on skeletal muscle which improves insulin sensitivity. The benefits are lost if exercise isn't regular (at least every other day).

    • Overtraining: Excessive exercise can lead to cardiac fibrosis and liver fibrosis.

  • Follow-up Study (CALERIE): A multi-center study involving 220 people aged 20-50 with a BMI of 22-28. Participants were randomized to 25% calorie restriction or control for two years.

    • Participants achieved an average 13% calorie restriction. There were improvements in cardiometabolic factors (LDL cholesterol, HDL cholesterol, triglycerides, systolic/diastolic blood pressure), and insulin sensitivity.

    • The metabolic profiles in participants even slightly overweight were improved.

  • Framingham Heart Study: Individuals who are 50 years old were measured for LDL cholesterol (less than 4.6 untreated), blood pressure (less than 120/80 untreated), non-smokers, non-diabetic, and BMI less than 25, they had a 5% risk of cardiovascular disease in their remaining life. Those with one abnormal factor had a 50% risk, and those with two or more had a 70% risk.

  • Urinary F2-isoprostanes: Calorie restriction significantly reduces F2-isoprostanes, a marker of oxidative stress. There was a reduction in C-reactive protein, TNF-alpha, white blood cells, neutrophils, and lymphocytes.

  • Clonal Hematopoiesis: High insulin, insulin resistance, and obesity lead to increased coronary bone marrow activation and inflammation in plaques. Two years of calorie restriction increased thymic volume and the production of T-regulatory cells mediated by PLA2G7.

  • Secondary Prevention: People with type 2 diabetes, abdominal obesity, and early-stage diabetic nephropathy were randomized to 25% calorie restriction or a standard diet for six months.

    • Calorie restriction reduced blood glucose, HbA1c, systolic/diastolic blood pressure, angiotensin II, C-reactive protein, albuminuria, and glomerular hyperfiltration.

    • Direct Randomized Clinical Trial: Those who lost more than 15 kg had 86% remission in type 2 diabetes at one year.

    • NASH (Nonalcoholic Steatohepatitis) Study: Individuals with NASH who lost more than 10% of their body weight had steatosis improvement (100%), NASH resolution (90%), and regression of fibrosis (81%).

    • Interventions impact metabolic, inflammatory, immune, growth factor, and aging pathways.

Guideline 2 & 3: Fruits, Vegetables, and Whole Grains

  • Choose a variety of fruits and vegetables and opt for whole grains over refined grains due to higher fiber content.

  • Dietary Fiber: Fiber lowers cholesterol absorption, increases fecal bile acid excretion, reduces HMG-CoA reductase activity, reduces inflammation, improves gut permeability, increases gastric distension, slows gastric emptying, and produces incretin-like hormones.

  • Comparison: Refined wheat drastically reduces fiber (18.5% vs. 1.9%), zinc, iron, selenium, and ferulic acid compared to whole wheat.

  • Fiber and proteins are two of the most important nutrients shaping gut microbiota composition and function.

  • Short-chain fatty acids (SCFAs) like propionate and butyrate, produced by gut microbiota, activate G-coupled receptors in epithelial and immune cells, leading to anti-inflammatory and autoimmune responses.

  • Phytochemicals and vitamins in vegetables, whole grains, and beans influence cancer enzymes and detoxify carcinogenic substances.

  • Gut Microbiota Pharmacological: The same amount of medication because of the different composition of gut microbiota may influence the pharmacological activity/response of the same drug.

Guideline 4: Healthy Protein Sources

  1. Protein from plants.

  2. Fish and seafood.

  3. Low fat or fat free dairy products.

  4. Lean cuts of meat.

  • Combine whole grains and beans for all essential amino acids, as well as fiber, vitamins, and iron.

    Consumption of whole grains and beans have spherules that reduce LDL absorbtion

  • Seafood is rich in omega-3 and vitamin B12.

  • Excessive animal consumption can promote disease by consuming excess carnitine and choline. These nutrients are metabolized by gut bacteria into TMAO, which is pro-atherogenic. Higher TMAO concentrations are linked to a 20% higher risk of myocardial infarction and stroke.

    Saturated fatty acids are found in animal fats. A linear correlation exists between their intake and LDL cholesterol levels.

  • Processed meats are classified as group 1 carcinogens, and red meat is classified as a group 2A carcinogen.

  • Mediterranean Diet: Reduced the risk of high cardiac deaths compared to the American Heart Association step one diet.

  • Indo-Mediterranean diet: This diet reduces the rate of nonfatal myocardial infarction and the rate of cardiac death.

  • Mediterranean diet + Olive oil/Nuts: reduces major cardiovascular events in high-risk people.

Guideline 5. Use Plant Oils Rather Than Animal Fats

  • Animal fats and tropical oils are rich in saturated fatty acids.

  • Trans fatty acids are more atherogenic than saturated fatty acids because they increase LDL cholesterol, reduce SGL, increase triglycerides, and increase inflammation and endothelial dysfunction.

  • Olive oil is a good source of monounsaturated fatty acids and are rich in phenolic compounds, vitamin E, carotenoids, and oleocanthal, which inhibits platelet aggregation.

Guideline 6. Choose Minimally Processed Food Instead of Ultra Processed Food

  • Ultra-processed foods increases mortality. People fed ad-libitum on ultra-processed food gained around 1 kg in two weeks.

  • Kids get most of their calories from ultra-processed food.

Guideline 7. Limit Sugary Beverages

  • High fructose corn syrup are linked to weight gain, cause liver steatosis, insulin resistance, and endothelial dysfunctions.

  • Sugar free beverages trigger appetite and may have carcinogenic profiles.

Guideline 8. Limit Salt Intake

  • High sodium intake is related to High blood pressure

  • Reducing sodium and increasing potasium can reduce the risk of stroke

  • Be aware of hidden salt, especially in ultra-processed foods

  • Weight greatly affects blood pressure

Guideline 9. Limit Alcohol Intake

  • There is no protective effect of small amounts of alcohol to coronary heart disease and there is an increased risk of atrial fibrillation risk and stroke when intaking alcohol. So if you don't drink, don't start

    alcohol is is unsafe for your heart.

  • Alcohol has been proven to be procarcinogenic.

Guideline 10. Adhere to These Guidelines (Throughout Life)

*Cost for health care is estimated to triple in the next 40 years.

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Aging accumulates metabolic molecular damage. What you do before procreation is changing how your mRNA, and DNA are transcribed into mRNA and proteins.

  • Smoking, drinking, or if you are have type two diabetes, obesity, you are changing the epigenome.

  • Multiple evidence, mostly in animals that shows male also has an effect in shaping the epigenome.

  • At Any age you can change the slope of Accumulation of Molecular Damage.

Conclusion

There is no zero risk, but you can increase the risk or reduce the risk through what we do every single day, and it's never too late.

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There is an impact of mental health and emotional health, also compassion shapes important inflammatory immune pathways.

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