History and exam
Key diagnostic factors
common
chest pain
dyspnea on exertion
May be present with or without chest pain to indicate coronary disease or may be a symptom of congestive heart failure.[142]
hypotension
Presentation for acute coronary syndrome complicated by cardiogenic shock.[153]
rales
Could be suggestive of left ventricular dysfunction in the setting of acute coronary syndrome or congestive heart failure.
Patients with rales, S3 gallop, or acute mitral regurgitation have a very high likelihood of severe underlying coronary artery disease (CAD).[142]
S3 gallop
Suggestive of left ventricular dysfunction in the setting of acute coronary syndrome or congestive heart failure.
Patients with rales, S3 gallop, or acute mitral regurgitation have a very high likelihood of severe underlying CAD.[142]
hypertension
Blood pressure ≥130/80 mmHg is an established risk factor for atherosclerotic cardiovascular disease.[29]
nausea
Commonly associated with chest pain in acute coronary syndrome.[142]
diaphoresis
Commonly associated with chest pain in acute coronary syndrome.[142]
tachycardia
Commonly associated with chest pain in acute coronary syndrome, aortic dissection, or hemorrhagic stroke.[142]
uncommon
indigestion
An uncommon presentation for acute coronary syndrome. More common in women than men.[154]
Other diagnostic factors
common
unilateral weakness, numbness, and/or tingling
A presenting symptom in a significant proportion of patients with ischemic stroke.[155]
headache
One meta-analysis found that approximately 14% of patients with ischemic stroke have headache at the time of, or shortly following, their stroke diagnosis.[159]
intermittent claudication
The cardinal symptom of peripheral artery disease (PAD). An aching or burning in the muscles of the leg (calf, thigh, or buttock) that is reliably reproduced at a set distance of walking and is relieved within minutes on rest. It is never present at rest or exacerbated by position.[160]
Occurs in only 33% to 50% of patients with PAD.[139]
bruits
May be heard over narrowed vessels.[163]
uncommon
aphasia
Occurs in 30% of patients with ischemic stroke.[156]
hemisensory loss
May indicate cerebrovascular accident.[155]
cranial nerve palsies
Seen in some patients with stroke.[157]
seizures
An uncommon presentation of hemorrhagic or ischemic stroke.[158]
vertigo
Rare, but may be seen in patients with strokes involving the posterior circulation.[155]
limb pain at rest
Suggestive of critical limb ischemia.[160]
diminished/absent lower extremity pulses
Suggestive of compromised lower extremity circulation and may be indicative of critical limb ischemia.[160]
ulcers or gangrene
Suggestive of severe peripheral arterial disease and critical limb ischemia.[160]
peripheral edema
Often indicates heart failure or acute myocardial infarction with left ventricular dysfunction.[161]
smooth shiny skin with hair loss
Can be seen in peripheral artery disease.[162]
pallor
May occur in patients with acute coronary syndrome, shock, or hemorrhagic stroke.
Risk factors
strong
cigarette smoking
Cigarette smoking (both active and passive) is an independent risk factor for both cardiovascular disease (CVD) and diabetes.[47][48][49] The risk of developing diabetes is 30% to 40% higher for active smokers than nonsmokers and there is a positive dose-response relationship between the number of cigarettes smoked and the risk of developing diabetes.[50]
There is a well-established link between smoking cessation and reduction in CVD morbidity and mortality.[48]
hypertension
Hypertension occurs in 50% to 80% of patients with type 2 diabetes and 30% of patients with type 1 diabetes.[51] In patients with diabetes, coexistent hypertension further increases the risk for CVD, diabetic retinopathy, and renal insufficiency.[52][53][54] A 5 mmHg reduction of systolic blood pressure (BP) has been shown to reduce the risk of major cardiovascular (CV) events by about 10%.[55]
It is well accepted that BP control reduces CV risk in patients with diabetes; however, certain pivotal studies investigating the benefits of intensive (<120 mmHg) versus standard (<140 mmHg) BP control yielded discordant results.[56][57][58][59] Guidelines recommend a BP treatment goal of <130/80 mmHg, providing this can be safely attained.[6][29][60][61]
dyslipidemia
People with diabetes can have various types of dyslipidemia. However, a major risk factor for CVD in patients with type 2 diabetes is a distinctive atherogenic triad of hypertriglyceridemia, reduced high-density lipoprotein cholesterol (HDL-C), and increased small dense low-density lipoprotein cholesterol (LDL-C).[62][63]
poor glycemic control
A 1% increase in hemoglobin A1c (HbA1c) increases the risk of myocardial infarction, stroke, or peripheral arterial disease by 18% in people with diabetes.[47] Increases in fasting blood glucose in mid-life are also associated with increased risk for CVD later in life.[64] In addition, evidence suggests that higher HbA1c variability (indicating higher fluctuations in glucose levels) is associated with increased CVD risk.[65][66]
Evidence for intensive glycemic control decreasing risk of CVD is stronger in type 1 than type 2 diabetes; however, controlling HbA1c to <7% (<53 mmol/mol) is recommended in most patients with type 2 diabetes to improve clinical outcomes.[29][67] Achieving a target of <7% (<53 mmol/mol) has been shown to reduce CVD risk by 37% over 11 years.[47]
physical inactivity
Sedentary behavior and insufficient physical activity are established risk factors for CVD in people with and without diabetes.[68][69] Many individuals with type 2 diabetes do not meet the recommended exercise level per week.[29][70]
Increased physical activity decreases all-cause mortality and CVD-related mortality in type 2 diabetes.[47][71][72] One small-scale randomized controlled trial of patients with type 1 diabetes found that high-intensity interval training improved cardiac function and structure compared with standard of care.[73]
overweight and obesity
There is a clear correlation between increasing prevalence of diabetes and increasing body mass index (BMI), with overweight (BMI >25 kg/m²) and obesity (BMI >30 kg/m²) significantly increasing the risk of CV events in patients with type 1 and type 2 diabetes.[54][74][75]
It is estimated that obesity is associated with a twofold increased risk of CVD.[47] Obesity promotes CVD through its direct impact on cardiac functioning, and its indirect effects on hypertension, dyslipidemia, and inflammation.[47]
albuminuria
Albumin levels ≥30 mg/g creatinine are associated with increased CVD risk in patients with diabetes.[76]
In the Heart Outcomes and Prevention Evaluation (HOPE) trial, the presence of microalbuminuria was associated with a 1.97-fold increased relative risk of the primary aggregate end point (myocardial infarction [MI], stroke, or CVD death) among people with and without diabetes.[77] In the Losartan Intervention for Endpoint Reduction (LIFE) trial, every 10-fold increase in the albumin/creatinine ratio was associated with a 39% increased risk of CVD death, MI, or stroke among people with diabetes.[78] HOPE and LIFE findings are supported and strengthened by the results of a Danish cohort study of almost 70,000 patients with type 2 diabetes and no overt CVD.[79]
chronic kidney disease (CKD)
CKD is a risk factor for cardiovascular disease, independent of diabetes and other traditional risk factors such as hypertension and dyslipidemia. Worsening kidney function (lower glomerular filtration rate, increased albuminuria) is associated with progressively increased risk of coronary disease.[80]
elevated C-reactive protein
Among 746 men with diabetes followed for an average of 5 years, those in the highest quartile for C-reactive protein (CRP) had a 2.6-fold increased risk of CVD events compared with those in the lowest quartile.[81]
Elevated CRP has also been associated with increased CV risk and dyslipidemia in Korean and sub-Saharan African populations.[82][83]
family history of CVD
female sex
Diabetes has a significantly greater impact on risk of adverse CV outcomes in women than in men.[84][85][86][87][88][89]
One study encompassing >850,000 individuals found that diabetes conferred a 44% greater excess risk for coronary heart disease in women compared with men.[87] Another study found that women with type 1 diabetes had an 86% greater excess risk of fatality from CVD than men with type 1 diabetes.[84] Excess risk of heart failure associated with both type 1 diabetes and type 2 diabetes is also significantly greater in women than in men.[88]
There is a need for more research in this arena; however, potential mechanisms conferring excess risk include biologic/sex-specific factors, gender-related disparities, and traditional risk factors. Sex-specific factors include premature menopause, gestational diabetes, hypertensive diseases of pregnancy, breast cancer treatment, and systemic inflammatory or autoimmune disorders.[90][91]
Biologic factors such as early menopause (ages <45 years) and increased coronary artery calcification in women compared with men may also partly explain the difference in CVD risk.[84][91][92] Gender-related disparities such as intimate partner violence, psychosocial factors, and socioeconomic deprivation are also implicated.[90][92]
Transgender women, including those with diabetes, are also at higher risk for CVD, which observational data suggest may be due to estrogen use.[93]
Evidence for the effect of menopausal hormone therapy (MHT) on CVD outcomes in women with type 2 diabetes is mostly lacking due to no or limited inclusion of participants with diabetes in clinical studies. One study using pooled data from three landmark prospective CVD cohorts in the US found that MHT was associated with a small but statistically significant reduction in CVD risk among white, but not black, women with prediabetes or type 2 diabetes.[94]
A 2023 scientific statement from the American Heart Association on the impact of race and ethnicity on CVD risk factors in women noted that CVD is the leading cause of death in women, with risk varying between different racial and ethnic groups.[95] It suggested that there is a need for an expanded approach to risk factors and primary prevention strategies for CVD in women of underrepresented races and ethnicities, who are particularly vulnerable to health disparities.[95]
gestational diabetes
mental illness
Patients with severe mental illness have an increased risk of both type 2 diabetes and CVD, with a two- to fourfold higher rate of diabetes, hypertension, dyslipidemia, and metabolic syndrome compared with the general population.[98] Diabetes can be exacerbated by antipsychotic treatments which alter glucose metabolism and promote weight gain. Furthermore, these patients are more likely to smoke, be obese, have obstructive sleep apnoea, live a sedentary lifestyle, and eat unhealthily, leading to an increased risk of CVD.[98]
The PRIMROSE (PRedIction and Management of cardiovascular Risk in peOple with SEvere mental illnesses) lipid model and the PRIMROSE body mass index model have been specifically developed and validated to predict the 10-year risk of incident CVD events in patients with severe mental illness.[99] The PRIMROSE model demonstrated that additional risk factors contributed to the development of CVD including social deprivation, severe mental illness subtype, prescriptions for antidepressants and antipsychotics, and reports of alcohol abuse.
One study found that loneliness was associated with a higher risk of CVD among patients with diabetes.[100] Loneliness showed a weaker influence than kidney function, cholesterol, and BMI, but a stronger influence than depression, smoking, physical activity, and diet.
metabolic dysfunction-associated steatotic liver disease (previously nonalcoholic fatty liver disease)
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