There are many additional evidences for the inreased
CV risk in CS. For example, approximately 80% of patients with CS have an increased albumin excretion in the urine, 61.5% have microalbuminuria (80). Endothelial dysfunction may develop in the preclinical phase
of vascular disease in patients with CS (68).

Carotid intima-media thickness is increased in CS (80)(22). Higher carotid intima media thickness and lower
systolic lumen diameter and distensibility coefficient were found in 25
patients with Cushing’s disease than controls  (38)(84). Carotid artery wall thickness and stiffness
remained increased in patients with CS one year after successful treatment.
Carotid wall plaques were detected in 32% of CS patients with active disease
and 30% of those in remission (3).

Cardiac hypertrophy is a common finding, even in the absence of AHT. The LVH is more severe in CS than in essential and other
secondary AHT, and can regress dramatically after
CS treatment (95). A study evaluating patients with active CS
demonstrated the presence of an abnormal left ventricular (LV) geometry with
increased LV mass index and relative wall thickness, which was associated with
LV diastolic dysfunction, but preserved LV systolic function (35). The abnormalities in the LV structure and
function in patients with CS are reversible upon normalization of corticosteroid
excess (96) (6).

Patients
with CS may have impaired systolic function as well as cardiac hypertrophy,
which correlate with the duration of cortisol excess, suggesting that cortisol
excess per se may play a significant role (95), (70). A characteristic alteration of
cardiac structure is found in CS – high relative wall thickness, reduced
midwall systolic performance and diastolic dysfunction. They may contribute
to the high risk of CV events observed in CS (70). Ma et al. proposed that cardiac
dysfunction in CS might be a manifestation of lipotoxic heart disease (95). ECG, 24h ambulatory BP monitoring,
echocardiography, OGTT and carotid artery ultrasonography are suggested for CS
patients (22).

There
is no reason to believe that CS patients smoke
less then others. CS patients might have even higher prevalence of smoking.
Namely, exogenous (iatrogenic) CS might be the result of administration of
glucocorticoids for a neoplasm or chronic obstructive lung disease (for which
smoking is a RF).

Insufficient
exercise can be reasonably expected
in higher percentage among CS patients. Specifically, CS patients per se,
especially those with pituitary or adrenal tumor are less likely to exercise,
because of obesity, fatigue, psychical problems, etc. Over 80% of CS patients
have symptoms consistent with an episode of major depression (75). Moreover, numerous
diseases – which require glucocorticoid treatment – are severe, as a rule (e.g.
lymphoma, rheumatoid arthritis, etc), precluding regular exercise. Indeed,
there is no definitive evidence for increased smoking prevalence and lack of
physical activity in CS patients.

In 22-32% of CS
patients hypokalemia can be found (97), which is well recognized arrhythmogenic factor, and
may lead even to fatal ventricular arrhythmias. Glucocorticoids are immunosuppressive agents and increase susceptibility to infections (98). Infections
may contribute to ACS pathogenesis.