Renal Athersosclerotic reVascularization Evaluation (RAVE Study): Study protocol of a randomized trial [NCT00127738]

BACKGROUND: It is uncertain whether patients with renal vascular disease will have renal or mortality benefit from re-establishing renal blood flow with renal revascularization procedures. The RAVE study will compare renal revascularization to medical management for people with atherosclerotic renal vascular disease (ARVD) and the indication for revascularization. Patients will be assessed for the standard nephrology research outcomes of progression to doubling of creatinine, need for dialysis, and death, as well as other cardiovascular outcomes. We will also establish whether the use of a new inexpensive, simple and available ultrasound test, the renal resistance index (RRI), can identify patients with renal vascular disease who will not benefit from renal revascularization procedures[1]. METHODS/DESIGN: This single center randomized, parallel group, pilot study comparing renal revascularization with medical therapy alone will help establish an infrastructure and test the feasibility of answering this important question in clinical nephrology. The main outcome will be a composite of death, dialysis and doubling of creatinine. Knowledge from this study will be used to better understand the natural history of patients diagnosed with renal vascular disease in anticipation of a Canadian multicenter trial. Data collected from this study will also inform the Canadian Hypertension Education Program (CHEP) Clinical Practice Guidelines for the management of Renal and Renal Vascular Disease. The expectation is that this program for ARVD, will enable community based programs to implement a comprehensive guidelines based diagnostic and treatment program, help create an evidence based approach for the management of patients with this condition, and possibly reduce or halt the progression of kidney disease in these patients. DISCUSSION: Results from this study will determine the feasibility of a multicentered study for the management of renovascular disease

Chapter 109 Hypertension and Hypothyroidism: A thyroid dysfunction frequently associated with an abnormal dietary iodine intake

Abstract Hypertension is a very common disorder. One-third of the United States population have hypertension or are taking anti-hypertensive medications. In addition, 45 million adults in the United States (20% of total population) suffer from pre-hypertension. Hypertension cannot be classified solely by discrete blood pressure thresholds. An important emerging concept is that hypertension is frequently associated with additional co-morbidities that contribute to increasing cardiovascular risk. Actually, hypertension represents a major risk factor for vascular, cardiac, renal and cerebral pathology so that the existence of so- called target organ damage (in vessels, heart, kidney and brain) is a criterion for assessing the clinical severity of the disease. Hypothyroidism represents the most common thyroid function disorder; worldwide, the prevalence of hypothyroidism varies by iodine intake and clearly increases with age, by reaching up to 20% in women older than 60 years. The foremost cause of congenital hypothyroidism remains endemic iodine deficiency and in adults chronic autoimmune (Hashimoto) thyroiditis that is more common in geographic areas of higher dietary iodine. The presence of an association between hypothyroidism and hypertension is an acquisition that has been increasingly confirmed and validated over the time. Results rising from the bulk of the studies suggest a convincing association between hypertension and hypothyroidism, with a prevalence of hypertension in hypothyroid subjects, particularly of elevated diastolic blood pressure nearly triple than that seen in the general population. In subjects over 50 years of age, overall data indicate a 30% prevalence of hypertension in hypothyroid subjects. Moreover, population-based studies revealed the presence of an unrecognized hypothyroidism in 3-5% of untreated hypertensive patients and indicate the existence of a continuous linear relationship between thyroid function and cardiovascular risk regarding what concerns both the atherogenic and metabolic profiles. However, the observed association between hypothyroidism and hypertension does not prove a causal relationship. Considerable further exploration is needed regarding on mechanisms of disease and in particular on the relationships between a hypothyroid state and other (neuro-) endocrine systems that may determine and worsen a hypertensive state. At the same time, new acquisition is necessary to increase our understanding of the role of thyroid hormone deficiency in target organ damage induced by hypertension

The role of thyroid hormone in blood pressure homeostasis: Evidence from short-term hypothyroidism in humans

Arterial hypertension is known to be frequently associated with thyroid dysfunction, with a particularly high prevalence in chronic hypothyroidism. However, to our knowledge no comprehensive study addressed causal mechanisms possibly involved in this association. We here report the physiological relationships between blood pressure and neuro-humoral modifications induced by acute hypothyroidism in normotensive subjects. Twelve normotensive patients with previous total thyroidectomy were studied. Ambulatory 24-h blood pressure monitoring was performed, and free T(3), free T(4), TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral L-T(4) withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During the hypothyroid state (TSH, 68.1 +/- 27.7 muIU/ml; mean +/- SD), daytime arterial systolic levels slightly, but significantly, increased (125.5 +/- 9.7 vs. 120.4 +/- 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 +/- 7.9 vs. 76.4 +/- 6.8 mm Hg; P < 0.001), noradrenaline (2954 +/- 1578 vs. 1574 +/- 962 pmol/liter; P < 0.001), and adrenaline (228.4 +/- 160 vs. 111.3 +/- 46.1 pmol/ liter; P < 0.05) also increased. PRA remained unchanged (0.49 +/- 0.37 vs. 0.35 +/- 0.21 ng/ml.h; P = NS), whereas both aldosterone (310.3 +/- 151 vs. 156.9 +/- 67.5 pmol/liter; P < 0.005) and cortisol. (409.2 +/- 239 vs. 250.9 +/- 113 pmol/liter; P < 0.02) significantly increased. By using univariate logistic regression daytime arterial diastolic values, noradrenaline and aldosterone were found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). In conclusion, our data show that thyroid hormones participate in the control of systemic arterial blood pressure homeostasis in normotensive subjects. The observed sympathetic and adrenal activation in hypothyroidism, which is reversible with thyroid hormone treatment, may also contribute to the development of arterial hypertension in human hypothyroidism

1. In hypertensive women, both the results of the screening for hyperaldosteronism and of the evaluation of insulin resistance depend on the timing of assessment in relation to the ovarian cycle

We have reported that in low-renin hypertensive women the increment of plasma aldosterone that occurs in the luteal compared to the follicular phase of the ovarian cycle markedly increases the positivity for suspected primary hyperaldosteronism; it has also been reported that aldosteronism is associated with insulin resistance (IR) (Garg J.Clin.Endocrinol.Metab, 2010) and that IR slightly but significantly increases in the luteal phase in normotensive women (Yeung J.Clin.Endocrinol.Metab, 2010). We here report the results of a study on 31 women in the fertile age evaluated because of arterial hypertension in whom both aldosterone and HOMA-IR index (glucose*insulin/405) levels were investigated during the ovarian cycle. All measures (plasma aldosterone, PRA, insulin, glucose and progesterone levels) were done at the 5-7th (follicular phase) and 21-25th (luteal phase) day of the menstrual cycle, without hypotensive therapy or with doxazosin 4mg per day. All women reported a regular cycle, age: 41.7±8.4 [mean±SD] (range:19-53) years, BMI 25.1±4.6 (19.3-35.8) kg/m2. Compared to the follicular phase, in the luteal phase plasma progesterone (P), aldosterone (ALDO), renin activity (PRA), insulin (I) and HOMA-IR all increased significantly: P from 0.6±0.3 to 8.7±4.1 ng/mL (p15 ng/dL with ALDO/PRA>40 increased from 7/31 (23%) to 16/31 (52%); the proportion of HOMA-IR>2.5 increased from 3/22 (14%) to 6/22 (27%). Multiple regression analysis demonstrated that P - but not ALDO - and BMI were strong positive independent predictors of plasma insulin and HOMA-IR: univariate analysis 1.) I vs P p=0.016; vs BMI p<0.0001; 2.) HOMA-IR vs P p=0.065; vs BMI p<0.0001; multivariate analysis 1.) I vs P (p=<0.002) + BMI (p<0.0001); 2.) HOMA-IR vs P (p<0.02) + BMI (p<0.0001). These results in hypertensive women confirm that plasma aldosterone may greatly increase during the luteal phase of the ovarian cycle and suggest that also insulin resistance may increase to a greater extent than in normotensive women. The ovarian cycle is thus a source of variability of plasma aldosterone and of insulin resistance in hypertensive women in fertile age, with potential relevance in the diagnostic workup and pathophysiology of hypertension

Low renin hypertension and mineralocorticoid excess

Low renin hypertension and mineralocorticoid excessP-639: Low renin hypertension and mineralocorticoid excess Mineralocorticoid excess has being increasingly diagnosed in arterial hypertension and is known to be associated with a low renin condition; however it may escape diagnosis in the absence of overt hypokalemia and aldosteronism. Aim of the study was to assess in hypertensive patients the relationship between a low renin profile and adrenal abnormalities evaluated by CT and adrenocortical scintigraphy. CT of the adrenal regions without contrast media injection was performed in 34 normokalemic hypertensive patients with low PRA levels(≤0,65 ng/ml/hr) and either high-normal or mildly elevated aldosterone levels (range 120–220 pg/ml) and in a series of eight hypertensive patients with comparable aldosterone but normal PRA levels (>0,65 ng/ml/hr). All patients had their antihypertensive treatment withdrawn and were under no salt restriction for at least one week at the time of laboratory examination. Iodomethyl-Nor-cholesterol adrenal scintigraphy under ACTH suppression by oral desamethasone was performed only in positive CT studies. Adrenal CT was normal in the control population but showed either bilateral or unilateral abnormalities in 20 low renin patients: bilateral hyperplasia (n=8), unilateral hyperplasia (n=3), unilateral nodule (n=9). Scintigraphy showed hyperfunctioning glands in 11 out of 16 patients who underwent the examination (8 bilaterally, 3 unilaterally). A low renin profile with inappropriately mantained aldosterone secretion in arterial hypertension may suggest adrenocortical hyperplasia or adenoma. A screening by means of adrenal CT is indicated, to be followed in the positive cases by adrenal scintigraphy or adrenal vein sampling. This workup could allow a correct diagnosis and tailored treatment