Myocardial Infarction (Heart Attack): Causes

Pathogenesis (development of disease)

Acute myocardial infarction occurs when blood flow in one of the coronary arteries (arteries that surround the heart in a wreath shape and supply blood to the heart muscle) suddenly dries up due to occlusion by a thrombus (“blood clot“). Even before complete occlusion, the coronary arteries show signs of narrowing due to atherosclerosis (hardening of the arteries) and lead to a restriction of the blood supply to the heart, which can manifest itself as angina pectoris symptoms (“chest tightness”; sudden pain in the region of the heart). Slowly developing coronary artery stenoses (narrowing of the coronary arteries) rarely lead to myocardial infarction because a well-developed collateral network (replacement network) can form over time. The extent of damage to the heart from arterial occlusion depends on:

• Supply area of the affected coronary vessel (coronary artery).
• Extent of vessel occlusion (vessel occlusion complete or not).
• Duration of the vessel occlusion
• Amount of blood that can be delivered to the affected area of the heart through collaterals (replacement vessels)
• Oxygen demand of the heart tissue
• Individual factors that may cause spontaneous dissolution of the occluding thrombus

In approximately 25% of cases, myocardial infarction is caused by plaque erosion rather than plaque rupture. This shows a vascular structure that is intact.Plaque erosion sites are characterized by T-lymphocytes (special activated immune cells), which can accumulate in the wall of the coronary vessels (coronary arteries) under altered blood flow conditions and contribute to damage to the endothelium (inner wall of the vessel). If a myocardial infarction is present as a result of ischemia (reduced blood flow or a complete loss of blood flow) in acute coronary syndrome (e.g., plaque rupture, erosion, fissure, or dissection), it is referred to as a type 1 myocardial infarction (TIMI). In contrast, type 2 myocardial infarction (T2MI) is when there is myocardial damage resulting in a mismatch of myocardial oxygen supply and demand without causative lesion-related coronary vessel obstruction. The triggers for type 2 myocardial infarction may include coronary endothelial dysfunction, coronary artery spasm, coronary embolism, arrhythmias, hypotension and hypertension (high blood pressure) with or without left ventricular hypertrophy (LVH), heart failure, anemia (anemia), respiratory failure, or renal failure. In a review of 14 studies, the most common triggers of type 2 myocardial infarction (T2MI) included tachyarrhythmias (a combination of arrhythmia and tachycardia), anemia, hypertension, infection or sepsis, respiratory failure, hypotension, heart failure, and postoperative factors. In approximately 10% of cases, non-obstructive coronary arteries (unobstructed coronary arteries) are present in myocardial infarction. The term MINOCA (myocardial infarction with non-obstructive coronary arteries) was coined for these cases. Patients present with STEMI (synonyms: ST-segment elevation myocardial infarction) and at the same time do not show relevant stenoses of the epicardial vessels (> 50%) on angiography [see ESC guidelines]. Note: Mortality (death rate) in the MINOCA group was 3.2% at one year and 4.9% at two years; for recurrent nonfatal myocardial infarction, the risk was 7%.Myocardial infarction, the risk was 7%. The prevalence (disease incidence) of MINOCA is 6-15%. Women have the greatest prevalence.In a study of women with MINOCA using optical coherence tomography (OCT) and cardiac MRI (cardio-MRI/cardiac MRI) and “unclear” symptomatic troponin elevation, an ischemic cause (reduced blood flow) was found in two of three cases. Among the non-ischemic findings, myocarditis (inflammation of the heart muscle) was the most common, accounting for three-quarters. Myocardial infarction progresses through the following temporal stages:

• Acute phase – the first hours to 7 days.
• Healing phase – 7 to 28 days
• Stage of healed infarction – from day 29.

Etiology (causes)

Biographical causes

• Genetic burden – esp. high risk if 1st-degree relative with myocardial infarction before 60th birthdayGenetic risk dependent on gene polymorphisms:
  • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
    • Genes: TGB3
    • SNP: rs5918 in gene TGB3 (affects thrombopoiesis).
      • Allele constellation: CT (2.8-fold increased risk of developing myocardial infarction; 6.2-fold increased risk of developing myocardial infarction before age 60)
      • Allele constellation: CC (> 2.8-fold risk of developing a myocardial infarction; > 6.2-fold increased risk of developing a myocardial infarction before the age of 60)
• Blood type – people with blood types A, B, or AB have a slightly increased risk of having a myocardial infarction (11,437 (1.5 percent) suffered a myocardial infarction compared with 7,220 of 771,113 people (1.4 percent) with a blood type of 0)
• Age – increasing age
• Height – inverse correlation between height and risk of myocardial infarction; patients who developed the disease before age 40 were 5 cm shorter than the normal population; a likely cause is an unfavorable lipid profile
• Hormonal factors – climacteric praecox (premature menopause; premature menopause; in this case, before age 45) (relative risk 1.11; 95% confidence interval 1.03-1.20).
• Socioeconomic factors – financial worries (13-fold risk).

Behavioral causes

• Nutrition
  • Excessive caloric intake and high-fat diet (high intake of saturated fatty acids, trans fatty acids – found especially in convenience foods, frozen foods, fast foods, snacks).
  • Increased homocysteine due to deficiency of vitamin B6, B12 and folic acid.
  • Daily consumption of unprocessed or processed red meat, ie muscle meat of pork, beef, lamb, veal, mutton, horse, sheep, goat.
  • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
• Consumption of stimulants
  • Alcohol – (woman: > 20 g/day; man: > 30 g/day); immediately after moderate alcohol consumption, there is a higher cardiovascular risk (myocardial infarction, apoplexy), which falls off after 24 h as, subsequently, there is even a relative protection against myocardial infarction and hemorrhagic stroke (≈ 2-4 drinks: relative risk = 30% lower risk) and protection against ischemic stroke within 1 week (≈ 6 drinks: 19% lower risk).
  • Tobacco (smoking, passive smoking); <50 yr 8-fold higher risk.
  • Snus (oral tobacco: tobacco mixed with salts, which is put under the upper or lower lip).
• Drug use
  • Cannabis (hashish and marijuana)
    • 4.8-fold higher risk within one hour of marijuana use
    • Risk factor for perioperative complications: active cannabis users were 88% more likely to suffer a heart attack in the hospital after surgery (adjusted odds ratio 1.88; 95% confidence interval 1.31 to 2.69)
  • Cocaine
  • Methamphetamine (“crystal meth”)
• Physical activity
  • Physical inactivity; the most important risk factor in women > 30 years of age.
  • Effort while shoveling snow; one-third of all heart attacks are on days with heavier snowfall (Canada)
• Psycho-social situation
  • Anxiety (10-fold increased risk)
  • Lonely and socially isolated people (+42%).
  • Stress (including work stress).
  • Anger attack (trigger; in the first two hours, the risk increases by a factor of 4); 8.5-fold increased risk
  • Long working hours (> 55 h/week).
• Sleep duration
  • Sleep duration 9-10 hours – In a large-scale study, it was observed that people who slept 9-10 hours were 10% more likely to suffer cardiovascular events such as myocardial infarction (heart attack) than those who slept 6-8 hours. If the sleep duration was more than 10 hours, the risk increased to 28%.
• Poor dental hygiene – this can lead to gingivitis (inflammation of the gums) or periodontitis (inflammation of the periodontium) and, as a result, infectious agents can penetrate through the oral cavity, promoting atherosclerosis
• Overweight (BMI ≥ 25; obesity)?- Monozygotic (identical) twins also have a similar risk of myocardial infarction when the risk of the heavier twin is compared with that of the lighter twin.
• Android body fat distribution, that is, abdominal/visceral truncal central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is present When waist circumference is measured according to the International Diabetes Federation (IDF, 2005) guideline, the following standard values apply:
  • Men < 94 cm
  • Women < 80 cm

  The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes

• Atherosclerosis (arteriosclerosis, hardening of the arteries) → coronary heart disease (CHD).
• Chronic obstructive pulmonary disease (COPD) with acute excavation – 3.7-fold risk of MACE (myocardial infarction/heart attack (OR 3.6), apoplexy/stroke (OR 2.8), cardiovascular-related death (OR 4.3)); in the first 4 weeks after excavation, the risk of infarction is highest
• Depression-independent cause of increased mortality after myocardial infarction.
• Diabetes mellitus or insulin resistance (decreased efficacy of endogenous insulin at target organs skeletal muscle, adipose tissue, and liver)
• Gout (arthritis urica/uric acid-related joint inflammation or tophic gout).
• Herpes zoster (shingles) – increased by a factor of 1.7 (1.47-1.92) in the first week after disease onset; risk decreased gradually in subsequent weeks but was increased overall over a 6-month period after disease onset
• Hypertension (high blood pressure)
• Infections
  • Skin infections: Patients with a skin infection had a 5-fold increased risk in the 7-day window
  • Respiratory infections:
    • Patients with a skin infection had a 2.9-fold increased risk in the 7-day window
    • Risk on days 1-7 of respiratory infection increased 17-fold; association was independent of age (below or above 60 years); weaker if
      • Male
      • History of myocardial infarction (medical history).
      • Excessively high cholesterol or blood pressure levels.
      • Before myocardial infarction intake of: Acetylsalicylic acid (ASA), antiplatelet drugs, beta blockers, ACE inhibitors or statins.
  • Influenza (flu)
    • Infections with type B influenza viruses are more dangerous than influenza A
    • Risk of illness increases 6-fold during first 7 days of influenza; no increased incidence observed thereafter
  • Pneumococcal pneumonia: incidence of myocardial infarction is 7 to 8%.
• Insomnia (sleep disorders)
• Migraine (vascular dysfunction) – 42% higher risk of myocardial infarction in men.
• Periodontitis (inflammation of the periodontium).
• Patients with pre-existing angina pectoris (“chest tightness”; sudden pain in the heart area).
• Sleep apnea syndrome – nocturnal respiratory regulation disorder.
• Subclinical inflammation (English “silent inflammation”) – permanent systemic inflammation (inflammation that affects the entire organism), which runs without clinical symptoms.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

• Elevated blood calcium levels: health risk estimation based on Mendelian randomization of defined SNPs: 0.5 mg/dl increase in calcium level (which is approximately one standard deviation) = 25% increased risk of myocardial infarction, 24% increased risk of coronary artery disease (CAD).
• Elevated C-reactive protein (CRP) (inflammatory marker).
• Increased uric acid level
• Increased homocysteine blood level – promotes atherosclerosis.
• HbA1c: regardless of diabetes status, increasing HbA1c increases the risk of myocardial infarction to the same extent for both sexes: for every one percentage point increase, the risk of myocardial infarction increased by 18% in relative terms, regardless of diabetes status
• Hyperlipoproteinemia (lipid metabolism disorders) – especially increased LDL and lowered HDL cholesterol and increased triglycerides.
• 25-OH-D (calcifediol) – even moderately decreased serum 25-OH-D levels are associated with an increased risk of myocardial infarction for men

Medications

• Clarithromycin – within 14 days of initiation of therapy, increased risk of myocardial infarction, among other things.
• Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, diclofenac) incl. COX-2 inhibitors (synonyms: COX-2 inhibitors; commonly: coxibs; e.g. Celecoxib, etoricoxib, parecoxib); already in the first week of therapy, the risk of myocardial infarction increases by 20-50%NSAIDs led to a 3.4-fold increased risk of myocardial infarction in the presence of respiratory disease, respiratory disease alone increased the risk by 2.7-fold, whereas NSAID use alone increased the risk by 1.5-fold. Intravenous therapy with an NSAID for respiratory infections increased the risk of subsequent myocardial infarction by 7.2-fold No significant increased rate of vascular death has been demonstrated for naproxen and acetylsalicylic acid. Both are inhibitors (inhibitors) of cyclooxygenase COX-1.
• Proton pump inhibitors (PPIs; acid blockers):
  • In patients taking them for heartburnNote that many PPIs are degraded via the liver enzyme CYP3A4, which is also required for the activation of clopidogrel (antiplatelet agent). Accordingly, one study demonstrated that concomitant use of, for example, omeprazole with clopidogrel lowers the plasma level of clopidogrel.
  • Long-term PPI users were 16-21% more likely to develop myocardial infarctions

Environmental exposure – intoxications (poisonings).

• Heat
• Winter: Myocardial infarction frequency increased by 7% when daytime temperature dropped by 10°C
• Air pollutants
  • “Asian dust” (sand particles, soil particles, chemical pollutants, and bacteria): acute myocardial infarctions were 45% more likely to occur one day after Asian-dust weather than on other days
  • Particulate matter from wood burning – increased risk of myocardial infarction in those over 65 years of age; esp. during cold spells (< 6.4 °C three-day mean); neither NO2 nor air ozone levels significantly affected outcome
  • Nitrogen dioxide and particulate matter pollution levels.
• Days with heavy pollen count (> 95 pollen grains per m3 air) (+ 5%).
• Weather:
  • Low outdoor temperatures (four more heart attacks when the average temperature fell below 0°C than when it was above 10°C).
  • High wind speed
  • Little sunlight
  • High humidity

Further

• Perioperative administration of only one red blood cell concentrate.