Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of > or =3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP ...that requires > or =4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. This classically defined resistant group consists of patients with true resistant hypertension, controlled resistant hypertension and pseudo-resistant hypertension. In studies where pseudo-resistant hypertension cannot be excluded (for example, 24-h ambulatory BP not obtained), the term apparent resistant hypertension has been used to identify 'apparent' lack of control on > or =3 medications. Large, well-designed studies have recently reported the prevalence of resistant hypertension. Pooling prevalence data from these studies and others within North America and Europe with a combined sample size of >600,000 hypertensive participants, the prevalence of resistant hypertension is 14.8% of treated hypertensive patients and 12.5% of all hypertensives. However, the prevalence of true resistant hypertension, defined as uncontrolled both by office and 24-h ambulatory BP monitoring with confirmed medication adherence, may be more meaningful in terms of identifying risk and estimating benefit from newer therapies like renal denervation. Rates of cardiovascular events and mortality follow mean 24-h ambulatory BPs in patients with resistant hypertension, and true resistant hypertension represents the highest risk. The prevalence of true resistant hypertension has not been directly measured in large trials; however, combined data from smaller studies suggest that true resistant hypertension is present in half of the patients with resistant hypertension who are uncontrolled in the office. Our pooled analysis shows prevalence rates of 10.1% and 7.9% for uncontrolled resistant hypertension among individuals treated for hypertension and all hypertensive individuals, respectively.
Obstructive sleep apnoea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is strongly associated with an increased risk of prevalent hypertension, whereas ...prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure (BP). Determining why OSA is so strongly linked to having hypertension in cross-sectional studies, but yet CPAP therapy has limited BP benefit needs further exploration. The CPAP studies do, however, indicate a wide variation in the BP effects of CPAP, with some patients manifesting a large antihypertensive benefit such that a meaningful BP effect can be anticipated in some individuals. OSA is particularly common in patients with resistant hypertension (RHTN). The reason for this high prevalence of OSA is not fully explained, but data suggest that it may be related to the high occurrence of hyperaldosteronism in patients with RHTN. In patients with RHTN, it has been shown that aldosterone levels correlate with severity of OSA and that blockade of aldosterone reduces the severity of OSA. Overall, these findings are consistent with aldosterone excess contributing to worsening of underlying OSA. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid within the neck, which then contributes to increased upper airway resistance.
Obstructive sleep apnoea (OSA) and hyperaldosteronism are very common in subjects with resistant hypertension. We hypothesized that aldosterone-mediated chronic fluid retention may influence OSA ...severity in patients with resistant hypertension. We tested this in an open-label evaluation by assessing the changes in the severity of OSA in patients with resistant hypertension after treatment with spironolactone. Subjects with resistant hypertension (clinical blood pressure (BP) >or=140/90 mm Hg on >or=3 antihypertensive medications, including a thiazide diuretic and OSA (defined as an apnoea-hypopnoea index (AHI) >or=15) had full diagnostic, polysomnography before and 8 weeks after spironolactone (25-50 mg a day) was added to their ongoing antihypertensive therapy. In all, 12 patients (mean age 56 years and body mass index 36.8 kg m(-2)) were evaluated. After treatment with spironolactone, the AHI (39.8+/-19.5 vs 22.0+/-6.8 events/h; P<0.05) and hypoxic index (13.6+/-10.8 vs 6.7+/-6.6 events/h; P<0.05), weight and clinic and ambulatory BP were significantly reduced. Plasma renin activity (PRA) and serum creatinine were significantly higher. This study provides preliminary evidence that treatment with a mineralocorticoid receptor antagonist substantially reduces the severity of OSA. If confirmed in a randomized assessment, it will support aldosterone-mediated chronic fluid retention as an important mediator of OSA severity in patients with resistant hypertension.
Aims
To identify clinically useful associations between HbA1c levels and various continuous glucose monitoring‐derived metrics.
Methods
We retrospectively analysed end‐of‐study HbA1c levels and >2 ...weeks of continuous glucose monitoring data collected from 530 adults with Type 1 diabetes or insulin‐requiring Type 2 diabetes during four randomized trials. Each trial lasted ≥24 weeks and provided central laboratory end‐of‐study HbA1c levels and continuous glucose monitoring data from the preceding 3 months. Participants were assigned to groups based on either HbA1c levels or continuous glucose monitoring‐derived glucose values.
Results
HbA1c was strongly correlated with mean glucose value (r=0.80), time spent with glucose values in the 3.9–10.0 mmol/l range (time in range; r=–0.75) and percentage of glucose values >13.9 mmol/l (r=0.72), but was weakly correlated with the percentage of glucose values <3.9 mmol/l (r=–0.39) or <3.0 mmol/l (r=–0.21). The median percentage of glucose values <3.0 mmol/l was <1.2% (<20 min/day) for all HbA1c‐based groups, but the median percentage of values >13.9 mmol/l varied from 2.5% (0.6 h/day) to 27.8% (6.7 h/day) in the lowest and highest HbA1c groups, respectively. More than 90% of participants with either <2% of glucose values >13.9 mmol/l, mean glucose <7.8 mmol/l, or time in range >80% had HbA1c levels ≤53 mmol/mol (≤7.0%). For participants with HbA1c ≥64 mmol/mol (≥8.0%), the median time in range was 44%, with 90% of participants having a time in range of <59%.
Conclusions
The associations shown in the present study suggest that continuous glucose monitoring‐derived metrics may help guide diabetes therapy intensification efforts in an HbA1c‐independent manner.
What's new?
Glycaemic control can be assessed with HbA1c or with descriptive statistics from continuous glucose monitoring (CGM) data. HbA1c is highly correlated with the average CGM‐derived glucose value.
Using HbA1c and CGM data from recently completed clinical trials, we found HbA1c to be highly correlated with the percentage of CGM values indicating hyperglycaemia, but poorly correlated with the percentage of CGM values indicating hypoglycaemia.
Because CGM data revealed hypoglycaemia among participants with HbA1c values ≥69 mmol/mol (≥8.5%), relaxation of HbA1c goals is not an effective strategy for hypoglycaemia prevention.
CGM‐based heuristics to guide therapy intensification efforts independently of HbA1c are also described.
The purpose of this study was to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. The FACT/GOG-Ntx is the FACT-G plus an ...eleven-item subscale (Ntx subscale) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. Two groups of women with ovarian cancer completed the FACT/GOG-Ntx: one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer. Levels of patient neuropathy, severity of toxicity, and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed. The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups, demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy. The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life. The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time.
ABSTRACT—Hypertension resistant to 2 antihypertensive drugs is more common among obese patients than among lean patients. The case we describe and the observations we report suggest that ...refractoriness among obese hypertensives is frequently caused by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels. In other words, obese hypertensives may have sleep apnea, obese hypertensives without sleep apnea may have inappropriately elevated levels of plasma aldosterone, and a surprising number of obese patients with sleep apnea also have elevated levels of aldosterone. The mechanisms by which obesity and obstructive sleep apnea increase aldosterone levels and raise blood pressure are not understood, but sympathetic nervous system activation and production of nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can be detected with a careful history and various sleep studies. Inappropriately elevated aldosterone levels can be detected by measuring the ratio of plasma aldosterone concentration to plasma renin activity. Successful treatment of these resistant hypertensives often can be achieved by devices that provide positive pressure to the upper airway to correct obstructive sleep apnea and by incorporating an aldosterone antagonist in the therapeutic regimen.
Hypertension is a major risk factor for the development and progression of chronic kidney disease (CKD). Mineralocorticoid receptor antagonists (MRAs) are effective in the management of resistant ...hypertension but are not widely used in CKD because of the risk of hyperkalemia. We retrospectively evaluated the long-term effects and safety of MRAs added to a pre-existing antihypertensive regimen in subjects with resistant hypertension associated with stage 3 CKD. In all, 32 patients were treated with spironolactone and 4 with eplerenone for a median follow-up of 312 days. MRAs induced a significant decrease in systolic blood pressure from 162±22 to 138±14 mm Hg (P<0.0001) and in diastolic blood pressure from 87±17 to 74±12 mm Hg (P<0.0001). Serum potassium increased from 4.0±0.5 to 4.4±0.5 mEq l(-1) (P=0.0001), with the highest value being 5.8 mEq l(-1). The serum creatinine increased from 1.5±0.3 to 1.8±0.5 mg dl(-1) (P=0.0004) and the estimated glomerular filtration rate decreased from 48.6±8.7 to 41.2±11.5 ml min(-1) per 1.73 m(2) (P=0.0002). One case of acute renal failure and three cases of significant hyperkalemia occurred. MRAs significantly reduced blood pressure in subjects with resistant hypertension associated with stage 3 CKD, although close biochemical monitoring is recommended because of an increased risk of hyperkalemia and worsening of renal function.
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