2 International Journal of Hypertension Table 1: Secondary forms of hypertension (disease categories). Table 2: Drugs inducing or exacerbating hypertension. (i) Endocrine disorders (ii) Renal disease (iii) Neurological disorders (iv) Acute stress (v) Drug-induced hypertension (vi) Miscellaneous disease), which are frequently encountered in hypertensive patients and are, therefore, the most interesting from the clinical point of view. In addition, this paper will attempt to provide a rational for the workup and treatment of patients with resistant hypertension. 2. Prevalence and Prognosis of Resistant Hypertension The exact prevalence of resistant hypertension in the general population remains unknown. Data from small observa- tional studies show a wide variation (from 5% to 50%) according to the studied populations [2–10]. Data from large clinical trials point towards a relatively high prevalence of resistant hypertension (20–35%). It has to be noted, however, that atypical drug combinations have been used in most of these studies as required by study protocols. Therefore, the evaluation of the prevalence of resistant hypertension requires a large, prospective, population-based study, specially designed for this aim. Similarly, the prognosis of resistant hypertension is currently unknown [2–10]. Available evidence addressing the prognosis of resistant hypertension is scarce, since virtually no longitudinal study has addressed this topic. Data from small clinical studies point towards an increased cardiovascular risk in patients with resistant hypertension. In addition, patients with resistant hypertension frequently have comorbidities that are known to increase cardiovascular morbidity and mortality, such as chronic kidney disease, diabetes, and obesity. Moreover, patients with resistant hypertension have higher rates of target organ damage than the general hypertensive population and are thus at increased cardiovascular risk. 3. Lifestyle Factors Resistance to antihypertensive treatment is aﬀected by several lifestyle factors. Excessive dietary salt intake is common in patients with resistant hypertension and contributes to treatment resistance by blunting the blood pressure reduc- tion of most antihypertensive drugs, including diuretics and inhibitors of the renin-angiotensin axis [2–10]. Obesity can also contribute to treatment resistance [2–10]. It has been shown that blood-pressure control is more diﬃcult to be achieved in obese than lean hypertensive patients. Several lines of evidence indicate a graded positive correlation between body mass index and blood pressure levels, while weight loss results in blood pressure reduction. (i) Nonsteroidal anti-inﬂammatory drugs (ii) Oral contraceptives (iii) Sympathomimetics (iv) Illicit drugs (v) Glucocorticoids (vi) Mineralocorticoids (vii) Cyclosporine, tacrolimus (iix) Erythropoietin (ix) Herbal supplements (x) VEGF inhibitors Insulin resistance, sympathetic nervous system overactivity, sodium retention, and activation of the renin-angiotensin system have been implicated in the pathogenesis of obesity- induced hypertension. Alcohol consumption is another important factor [2– 10]. Large alcohol consumption (>3 drinks per day) has been shown to result in blood pressure elevation. In addition, blood pressure control might be achieved more diﬃcult in heavy drinkers due to poor adherence in antihypertensive therapy. The role of physical inactivity in patients with resistant hypertension has not been adequately studied. 4. Drug-Induced Hypertension A variety of prescription or over the counter medicines as well as other exogenous substances may induce hypertension or contribute to treatment resistance. Drug-induced hyper- tension is among the most common causes of secondary hypertension and is frequently encountered in everyday clinical practice. However, despite the frequent occurrence of drug-induced hypertension, primary care physicians frequently miss the opportunity to detect and appropriately manage this iatrogenic form of secondary hypertension. Therefore, a detailed and meticulous medical history is of utmost importance in patients with resistant hypertension, since the identiﬁcation and subsequent withdrawal of the oﬀending drug may alleviate treatment resistance. However, withdrawal of the responsible agent is not always possible; in such cases, dose reduction and/or search for alternate treatment may substantially improve or even control blood pressure levels. Another very important aspect relates to the great variability of the eﬀects of administered drugs on blood pressure. The administration of oﬀending drugs can result in excessive blood pressure elevation in some individuals, while most individuals will experience little or no increases of blood pressure. This variability represents a rule without exception. Therefore, it would be very important to identify predictors of blood pressure elevation, in order to individu- alize drug treatment. Up to now, however, no such reliable predictors have been identiﬁed. A descriptive list of all exogenous agents capable of inducing or exaggerating hypertension is presented in Table 2. However, this paper will focus on the drugs that are