Ischemic heart disease, also known as coronary heart disease (CAD), is a condition where the myocardium receives insufficient blood flow as a result of epicardial coronary artery obstruction, typically brought on by atherosclerosis. CAD is a well-known common complex multifactorial disease that may be strongly influenced by environmental, genetic, and other risk factors, including hypertension, diabetes mellitus, dyslipidaemia, smoking, obesity, and so forth. Controlling CAD risk factors has been shown in numerous studies to significantly lower cardiovascular events in both symptomatic and asymptomatic individuals.Symptomatic patients may have acute (unstable) or chronic (chronic) disease. Most patients can be diagnosed with chronic coronary syndrome (CCS), also known as stable ischemic heart disease (SIHD), based on a traditional history of angina pectoris in the presence of atherosclerotic cardiovascular disease (ACD) risk factors or ACD that is already known to exist. Angina refers to the discomfort in the chest that develops when the myocardial oxygen demand exceeds the oxygen supply.
There is a lot of proof that dyslipidaemia is a major factor in the occurrence and mortality of CAD. The risk of CAD events can be significantly decreased by lowering plasma high cholesterol.
Dyslipidaemia is defined as lipid abnormalities with increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration.
Dyslipidaemia, as per ACC/AHA 208 guidelines is diagnosed if LDL-C ≥ 130 mg/dl, non HDL ≥ 160 mg/dl, HDL in men < 40 mg/dl, HDL in women < 50 mg/dl and serum triglycerides > 150 mg/dl.
(https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625)
Correlation of dyslipidaemia with age
Higher percentages of lipid abnormalities have been observed especially in the fourth to sixth decade of life. The prevalence of dyslipidaemia is highest in the age group of 50-65 years as shown in various studies. Historically, older age has been established as the most devastating contributor of dyslipidaemia.
Correlation of dyslipidaemia with gender
In patients with CAD, on comparison, women are 5 to 10 years older than men with the same baseline characteristics. The reason for this trend in women may be attributed to menopausal transition and loss of oestrogen at older age, which might act as a trigger factor and increase metabolic dysfunction.
Correlation of dyslipidaemia with diabetes
Patients with diabetes have altered lipid metabolism. Several factors may contribute to the altered lipid metabolism seen in patients with diabetes, such as insulin deficiency or resistance, adipocytokines, and hyperglycemia. Diabetic dyslipidaemia, a characteristic pattern, consists of low HDL-C, elevated triglycerides and lipemia which is post prandial.
How do you treat dyslipidaemia and reduce risk of CAD?
Any intervention that is aimed to treat dyslipidaemia and reduce blood cholesterol should also translate to reduction in risk of CAD or improvement in survival for patients with established CAD.
Life Style Modifications
Quitting smoking, getting more exercise, and improving your diet are all lifestyle changes that have significant positive effects on risk of CAD and death due to cardiovascular causes that start relatively soon after their institution.
Diet
People who choose healthy diets have significantly fewer CAD incidents. In patients with established CAD, dietary interventions—particularly the Mediterranean diet—improve outcomes.
The 2019 American College of Cardiology/American Heart Association (ACC/AHA) guideline on primary prevention of CAD includes the following dietary recommendations;
1) adherence to diets that emphasize high intakes of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish.
2) Diets should minimize the intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages.
A Mediterranean-style diet or one that is similar is advised in the European Society of Cardiology (ESC) guidelines on CAD prevention (both primary and secondary). They also advise reducing salt consumption, swapping saturated fats for unsaturated ones, choosing a diet high in fibre from plants, and eating fish, preferably fatty fish, at least once a week. At least one to two servings of oily fish per week for patients with known CAD or those at high risk who eat fish or are willing to do so, which is in line with the AHA recommendations.
Weight Reduction
Individuals who are overweight or obese have higher risks for CAD at a wide range of levels.Overweight and obesity may soon surpass smoking as the leading preventable cause of premature death in most wealthy nations. Weight loss is challenging to achieve and maintain; among the 90% of subjects who initially succeed, about 90% of those eventually put on the lost weight. However, it hasn't been conclusively shown that losing weight has a positive impact on cardiovascular outcomes.
Additionally, obesity and overweight play a significant role in the development of the metabolic syndrome, which is characterised by diabetes-causing hypertension, dyslipidaemia, and lipid abnormalities. About 40% of people over the age of 40 in wealthy nations have metabolic syndrome, which carries a high risk of a first CAD event. Additionally, obesity and overeating increase the risk of CAD significantly even in the absence of metabolic syndrome.
Physical Activity
Regular exercise has many cardiovascular advantages, including weight loss, better lipid profiles, lower blood pressure, and type 2 diabetes prevention and management. There are improvements in CAD morbidity and mortality as a result of all these positive effects.
The 2019 ACC/AHA primary prevention of CVD guideline's recommendation for physical activity also applies to secondary prevention: Adults should perform 75 minutes of vigorous exercise per week or at least 150 minutes of combined moderate and vigorous exercise per week.
Smoking Cessation
The benefits of quitting smoking on CAD are statistically significant and clinically significant, manifesting within a few months and reaching the non-smoker in three to five years.
In a meta-analysis of observational studies, among 12,603 smokers who had a prior myocardial infarction (MI), coronary artery bypass graft surgery, angioplasty, or known CAD, the relative risk (RR) of mortality for quitters compared with those who continued to smoke was 0.64 (95% CI 0.58-0.71) (Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA. 2003 Jul 2;290(1):86–97).
Alcohol
A number of negative consequences of excessive alcohol consumption include liver disease, heart failure (HF), an increased risk of cancer, neurologic complications, and unintentional injuries. The finding that moderate alcohol consumption, as opposed to abstinence or heavy drinking, may have sex-specific health benefits, particularly in regard to CAD and diabetes, serves to counteract these negative effects.
Light to moderate alcohol consumption has long been advocated as a way to lower cardiovascular risk by raising serum high-density lipoprotein (HDL) cholesterol levels. While it is possible after light to moderate alcohol consumption for serum HDL cholesterol to rise by 4 mg/dL, this shouldn't be anticipated.
Numerous clinical trials have shown that methods intended to increase HDL cholesterol as a means of lowering cardiovascular events are ineffective. But more research is needed to understand how alcohol affects various HDL functional measures.
There haven't been any extensive randomised studies on alcohol use. The available evidence comes from observational studies, which typically compare the traits of alcohol users with nonusers (including meta-analyses of numerous studies). Alcohol's apparent effects can therefore be confusing. For instance, moderate alcohol consumption is more prevalent among those with higher socioeconomic status, increasing the possibility that factors linked to higher socioeconomic status will confound the results.
Preventing Disease Progression
A high risk of subsequent CAD events, such as myocardial infarction (MI), stroke, and death, exists in patients with established CAD. Many individuals with multiple risk factors, metabolic syndrome, diabetes, or chronic kidney disease are also at extremely high risk even though they do not yet have established CAD.
Therapeutic lifestyle changes, such as increased physical activity, dietary modification/weight loss, and quitting smoking are of proven benefit and improve outcomes starting within a matter of weeks for all of these high-risk patients. Statins and aspirin are two additional adjunctive drug therapies with a history of success; their advantages are at the very least additive.
Medication
Statins
The risk of unfavourable cardiovascular events has been shown to be decreased by statins, ezetimibe, and PCSK9 inhibitors. The most thoroughly researched of these three are statins. LDL-C is reduced by 50–60% with high-intensity statin therapy. They outperform ezetimibe in terms of efficacy and are both cheaper and simpler to use than PCSK9 inhibitors. Furthermore, they have been in use for more than 30 years with excellent safety records. Statins are therefore the first option for almost all patients with elevated LDL-C levels.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a controlling enzyme for cholesterol biosynthesis, is effectively inhibited by statins through competitive inhibition.Pharmacological studies showed that statins can lower total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and raise HDL-C levels. Additionally, statins can stabilise coronary plaques, enhance endothelial function, and inhibit the inflammatory response!!!
Treatment with a high-intensity statin (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg daily) or the highest recommended dose is typically preferred in stable patients. If a patient does not lower their LDL-C levels as expected after taking the highest doses of either atorvastatin or rosuvastatin, it may be because they did not follow their doctor's instructions for a healthy lifestyle or because they responded differently to the treatment.
In patients with coronary artery disease or at high risk of developing cardiovascular disease, statins are well known to lower cardiovascular events and mortality. Statins have pleiotropic effects in addition to lowering LDL-C, including improved endothelial function, decreased inflammation, and decreased thrombus formation.
Regression of Atherosclerosis and Plaque Stabilization
The observation that coronary angiography has shown increases in lumen diameter at two and four years or a lesser degree of stenosis progression at three years after the start of statin therapy in various studies serves as an example of the benefit of lipid lowering.
Most patients with an acute coronary syndrome have a central component called coronary artery plaque rupture. More and more evidence also points to the fact that many of these patients have multiple unstable plaques in various coronary arteries, which suggests widespread inflammation in the coronary circulation. Therefore, targeting the culprit lesion alone with an intervention is unlikely to be the best course of action, and statins' ability to cause plaque stabilisation may be a key mechanism of benefit.
Statin therapy has been demonstrated to slow the progression of plaque formation and stabilise both ruptured and susceptible atherosclerotic plaques in studies.
Reduce Inflammation
Another significant factor in atherosclerosis and plaque rupture seems to be inflammation. Increased levels of inflammatory serum markers, particularly C-reactive protein (CRP), have been linked to the development of atherosclerosis, the risk of a first myocardial infarction in otherwise healthy men, and a worse prognosis in patients with stable and unstable angina and those who have coronary stenting. The serum CRP concentration is decreased as a result of statin therapy, whether it is used as primary or secondary prevention. Within 14 days, the serum CRP decrease starts.
Reversal of Endothelial Dysfunction
A common sign of endothelial dysfunction in atherosclerotic coronary arteries is the induction of vasoconstriction by acetylcholine rather than the anticipated vasodilation caused by nitric oxide. Nitric oxide, for example, which dilates blood vessels, and endothelin, which constricts blood vessels, work together to balance the tone of the arterial smooth muscle, with the former acting more strongly when the body is at rest.
Studies have shown that vasoconstriction associated with endothelial dysfunction can be attenuated or abolished with statin therapy, an effect that can improve overall vasodilator capacity and myocardial blood flow reserve within six weeks.
Decreased Thrombogenicity
The majority of acute coronary syndromes seem to be caused by thrombus formation at the site of plaque rupture. Lipid-lowering, especially when combined with statin therapy, has a number of effects that may lessen the formation of thrombus. These consist of: reduced tissue factor expression by macrophages and endothelial cells in the atherosclerotic plaque; reduced thrombin production and prothrombin activation; improved fibrinolytic profile; and Reduced platelet activation, possibly partially mediated by an antioxidant effect.
Numerous clinical studies conducted since the statins’ introduction in 1987 have shown that it reduces major cardiovascular events by lowering LDL-C levels, which has revolutionised the treatment of cardiovascular disease.
A drug with so many benefits. How safe is it?
Adverse effects of statins
Statins have been in use for more than 30 years with excellent safety records and are usually tolerated by majority of the patients. However, studies have reported statin related side effects such as myalgia, deranged liver enzymes, fatigue in 1-10% of the patients.
Moderate-intensity statin along with ezetimibe in patients who are intolerant to high-intensity statins is recommended.
Clinicians should try another statin that might be better tolerated or alternative dosing regimens, such as giving the medication every other day, often using low doses of rosuvastatin, in patients who cannot tolerate one statin due to myopathy.
Other lipid lowering drugs such as Ezetimibe or PCSK-9 inhibitors may also be used in patients who are intolerant to statins.
