It is well known that hypertension-mediated organ damage (HMOD) in vessels or organs (heart, brain, eyes, and kidney) is a marker of pre-clinical CVD associated with increased CV morbidity and mortality [26]. Therefore, knowledge of the presence of HMOD is of significant importance to better stratify CV risk and for the optimal management of hypertensive patients [26]. Several gender differences in HMOD have been described in the last years, and estrogens play a crucial role in HMOD pathogenesis [20].

Postmenopausal hypertensive women have more often ISH, reflecting an increase in AoS [27], more concentric left ventricular (LV) remodeling and less LV in response to arterial hypertension, resulting in a higher LV mass index and greater prevalence of HFpEF [18]. Moreover, in women, it has been demonstrated that the regression of hypertensive left ventricular hypertrophy (LVH) is more difficult to be obtained than in men, and residual hypertrophy is more common despite effective antihypertensive strategies and adequate BP control [28].

It is important to note that LVH has a well-demonstrated association with CV morbidity and mortality, and some studies have demonstrated that a higher LV mass index have a more significant impact on worse clinical outcome in women than in men [28].

Obesity, more prevalent in women than in men, may also potentiate the effect of hypertension on LVH in women, and the presence of increased body mass index (BMI) may be responsible, at least in part, for the lack of LVH regression as observed in the Strong Heart Study population [28,29].

Significant differences among male and female individuals were observed on vasculature damage, including arterial stiffness and intimate-medium thickness (IMT), carotid plaque size and compositions, and small arteries. Recently, extensive prospective studies showed that men have higher carotid IMT and carotid plaques than women at any decade of age. In contrast, women have less plaque burden, more stenosis, and a more positive remodeling of internal carotid arteries [30]. Intraplaque hemorrhage, a marker of plaque instability, is more frequent in men than women. Still, with increasing age, the probabilities of intraplaque carotid bleeding in women become closer to that of men [31]. It has been well assessed that arterial stiffness increases more significantly in women with aging, related to two-fold higher mortality than men [27].

Coronary microvascular dysfunction (CMD) leads to a significant increase in endothelial shear stress which negatively influences coronary anatomy and function and is strongly correlated with adverse CV events [32,33]. Moreover, the smaller coronary arteries size associated with a higher blood flow has been reported as a causal factor of a greater prevalence of CMD in women. In addition, the direct effect exerted by hypertension on microcirculation causes intramural arterioles’ remodeling and interstitial fibrosis. The reduction in microvascular density has also been involved in the development of CMD [32]. Nevertheless, estrogens have a protective role in premenopausal women [34]. The mechanism would seem due to early estrogen loss resulting in chronic activation of the RAAS [20]. Therefore the incidence of CMD significantly rises in postmenopausal women [32].

A more significant and earlier hypertension-related microvascular dysfunction in the female sex has been recently supported by the findings that the media/lumen (ML) ratio was higher in women than in men after correction for classical CV risk factors and age [35].

In contrast, microvascular obstruction areas (also knowns as “no-reflow”) following myocardial infarction (MI) remodeling are smaller in women and more presumably linked to distal atherothrombotic embolization, microvascular impairment, and reperfusion insult [36].

Microalbuminuria is a marker of CV and renal diseases, and it is a sign of HMOD in essential hypertension [37]. Irrespective of BP levels, microalbuminuria, urinary creatinine, and albumin excretion is lower in women [38]. Postmenopausal women have a more rapid deterioration of renal function, while BP control results in higher proteinuria lowering men than in women.

Experimental animal studies suggest a role for T regulatory cells and RAS system in sex differences in hypertensive kidney injury [39].

Hypertensive retinopathy (HR), which refers to retinal microvascular signs which develop in response to elevated BP, predicts stroke, congestive heart failure (CHF), and CV mortality, independently of traditional risk factors [40]. Hypertensive retinal vascular signs can be classified into arteriolar changes (narrowing of the retinal arteriolar vessels due to vasospasm and increased vascular tone, arterio-venous crossing or nicking, and arteriolar wall opacification), and more advanced retinal lesions (microaneurysms, retinal hemorrhages, cotton-wool spots, hard exudates, optic nerve ischemia, and optic disk swelling) [41].

HR is more prevalent in males than in women. This difference may be explained by differential distribution in risk factors [42]. It has been shown that antihypertensive therapy results in regression of HR and that this effect is mainly due to BP reduction and rather than antihypertensive drugs [43].