Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Patients with resistant hypertension have more peripheral arterial disease than other uncontrolled hypertensives.

The aim of this study was to investigate whether resistant hypertension differs from uncontrolled and controlled hypertension in terms of target organ damage. Hypertensive subjects with antihypertensive medication (n=385) were identified in a population survey conducted in southwestern Finland. None of the study subjects had previously diagnosed cardiovascular or renal disease or diabetes. Ankle-brachial index, estimated glomerular filtration rate, electrocardiogram-determined left ventricular hypertrophy and cardiometabolic risk factors were assessed. The prevalence of peripheral arterial disease among subjects with resistant, uncontrolled and controlled hypertension was 6/37 (16%), 22/275 (8%) and 0/73 (0%), respectively (P=0.006). There were no differences in the prevalence of renal insufficiency, left ventricular hypertrophy or metabolic parameters between the groups. Resistant hypertension affects vasculature more than uncontrolled hypertension, and thus it can be regarded as a marker of more severe disease.

Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes.

OBJECTIVES: Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. DESIGN: We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. RESULTS: During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. CONCLUSIONS: Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

Fabry disease: a review of current management strategies.

Fabry disease is an X-linked inherited condition due to the absence or reduction of alpha-galactosidase activity in lysosomes, that results in accumulation of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Manifestations of Fabry disease include serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischaemic attacks and strokes. Additional effects on the skin, eyes, ears, lungs and bones are often seen. The first symptoms of classic Fabry disease usually appear in childhood. Despite being X-linked, females can suffer the same severity of symptoms as males, and life expectancy is reduced in both females and males. Enzyme replacement therapy (ERT) can stabilize the progression of the disease. The rarity of the classic form of Fabry disease, however, means that there is a need to improve the knowledge and understanding that the majority of physicians have concerning Fabry disease, in order to avoid misdiagnosis and/or delayed diagnosis. This review aims to raise awareness of the signs and symptoms of Fabry disease; to provide a general diagnostic algorithm and to give an overview of the effects of ERT and concomitant treatments. We highlight a need to develop comprehensive international guidelines to optimize ERT and adjunctive therapy in patients with Fabry disease, including females and children.

Hypertensive women with the metabolic syndrome are at risk of renal insufficiency more than men in general population.

The prevalence of renal insufficiency in hypertensive participants without comorbidities affecting renal function is unknown. The objective of this study was to assess the prevalence and predictors of renal insufficiency in general hypertensive population. We examined 994 hypertensive participants aged 45-70 years without previously diagnosed diabetes, cardiovascular disease or chronic kidney disease. Renal insufficiency was defined as estimated glomerular filtration rate <60 ml min(-1) per 1.73 m(2) by the Modification of Diet in Renal Disease formula. The metabolic syndrome was defined according to the International Diabetes Federation and the US National Cholesterol Education Program Third Adult Treatment Panel criteria. Glucose homoeostasis was assessed with an oral glucose tolerance test. The prevalence of renal insufficiency was 6.7% (95% confidence interval (CI) 5.3-8.5). In a multivariate model, the presence of renal insufficiency was predicted by female gender (odds ratio (OR) 3.57 (95% CI 1.90-6.72)), older age (OR 1.13 (95% CI 1.07-1.18)), use of diuretics (OR 2.13 (95% CI 1.19-3.82)) and metabolic syndrome (OR 2.79 (95% CI 1.34-5.79)). Newly diagnosed diabetes or prediabetes did not predict renal insufficiency. The prevalence of renal insufficiency was found to be lower than previously reported in hypertensive general population. Metabolic syndrome, but not newly diagnosed diabetes or prediabetes per se, was strongly associated with renal insufficiency especially in women. Renal insufficiency was also associated with the use of diuretics, but the clinical relevance of this finding needs to be clarified.

Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Home-measured blood pressure is more strongly associated with electrocardiographic left ventricular hypertrophy than is clinic blood pressure: the Finn-HOME study.

Electrocardiographic evidence of left ventricular hypertrophy (ECG-LVH) has a grave prognostic significance in hypertensive patients. The purpose of our study was to assess whether ECG-LVH is more strongly associated with home-measured blood pressure (BP) than with clinic BP, and whether the correlation between home BP and ECG-LVH increases with the number of home measurements performed. We studied a representative sample of the general adult population (1989 subjects 45-74 years of age) in Finland. Subjects included in the study underwent a clinical interview, electrocardiography and measurement of clinic BP (mean of two clinic measurements) and home BP (mean of 14 duplicate home measurements performed during 1 week). Home BP correlated significantly better than clinic BP with the Sokolow-Lyon voltage (home/clinic systolic: r=0.23/0.22, P=0.60; diastolic: r=0.17/0.12, P=0.009), Cornell voltage (systolic: r=0.30/0.25, P=0.004; diastolic: r=0.21/0.12, P<0.001) and Cornell product (systolic: r=0.30/0.24, P=0.001; diastolic r=0.22/0.14, P<0.001) criteria of ECG-LVH. The correlation between home BP and ECG-LVH increased slightly with the number of home measurements, but even the mean of the initial two home BP measurements correlated equally well (systolic BP), or better (diastolic BP) with ECG-LVH than did clinic BP. In conclusion, home BP measurement allows us to obtain a large number of measurements that have a strong association with ECG-LVH. Our data support the application of home BP measurement in clinical practice.

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H2(15)O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3+/-1.2 vs 4.4+/-1.6, p=0.02), while the brachial artery flow-mediated dilatation was similar (5.9%+/-3.9% vs 4.5%+/-3.6%, p=0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.

Biochemical markers of types I and III collagen and limited joint mobility in type 1 diabetic patients.

Limited joint mobility (LJM), a long-term complication of diabetes, has been shown to be associated with microvascular complications of diabetes. Connective tissue alterations may contribute to the development of LJM and other diabetic complications. We tested whether biochemical markers of types I and III collagen metabolism are associated with LJM in type 1 diabetes. We studied 28 male patients of mean age 43.4 years (SD=9.5) and with a duration of diabetes of 25.2 years (SD=9.7) years. LJM assessment included goniometric measurements of the joints and classification by Rosenbloom's method. We measured serum concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP); urinary excretion of crosslinked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) was also measured. Although average serum PIIINP tended to be higher in subjects with moderate-severe LJM (3.1 +/- 1.3 microg/l) than in subjects with mild LJM (2.5 +/- 0.7 microg/l) or without LJM (2.6 +/- 0.4 microg/l), no significant association was found (p<0.27). Concentrations of the other collagen markers were not different in subjects with or without LJM. We conclude that synthesis and degradation of types I and III collagen in diabetic subjects with LJM did not differ from those without LJM to reflect changes in the biochemical markers of these proteins.

Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects.

AIMS: Connective tissue alterations may contribute to the development of diabetic long-term complications in eyes, kidneys and peripheral nerves. Collagen deposition may be increased in micro- and macrovascular disease in diabetic subjects. We tested whether biochemical markers of type III and I collagen metabolism are associated with retinopathy and neuropathy in Type 1 diabetes. METHODS: A total of 28 patients, mean age 43.4 +/- 9.5 (sd) and duration of diabetes 25.2 +/- 9.7 years, were studied. Stereoscopic colour fundus photographs were taken for assessment of retinopathy which was classified as no, background or proliferative. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and urinary excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: Average serum PIIINP was higher in subjects with proliferative (3.2 +/- 1.1 microg/l) than without proliferative retinopathy (2.5 +/- 0.6 microg/l) (P = 0.03). Average serum PICP was higher in subjects without retinopathy (181.7 +/- 19.5 microg/l) than in subjects with background retinopathy (132.1 +/- 42.7 microg/l) (P = 0.02). Concentrations of other collagen markers were not different in subjects with or without retinopathy. No association between collagen markers and neuropathy was found. CONCLUSIONS: The increased synthesis of type III collagen, reflecting deposition of matrix and basement membrane connective tissue, may be involved in the pathogenesis of proliferative retinopathy in Type 1 diabetic subjects. On the other hand, we observed decreased synthesis of Type I collagen, which can result in weakened vascular integrity in subjects with retinopathy.

Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes.

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.

ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.

The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE-inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation.

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition.

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Dupuytren's disease in type I diabetic subjects: investigation of biochemical markers of type III and I collagen.

OBJECTIVE: To clarify whether biochemical markers of collagen type III and I metabolism show alterations in type I diabetic subjects with Dupuytren's disease (DD) compared to those without DD. METHODS: DD was assessed in a total of 28 type I diabetic subjects, mean age 43.4 +/- 9.5 (SD) and duration of diabetes 25.2 +/- 9.7 years. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: The prevalence of DD was 32% (9 of 28 diabetic subjects). Average serum ICTP was 2.7 +/- 0.8 micrograms/l in subjects without DD and 3.6 +/- 1.2 micrograms/l with DD (p = 0.0276). No significant association between other collagen markers and DD was found. The reference intervals of PIIINP and ICTP were exceeded only in 1 and 2 subjects, respectively, and they both had DD. CONCLUSION: The degradation of type I collagen might be increased in diabetic subjects with DD. The overall implication was that synthesis or degradation of type III and I collagen in diabetic subjects with DD did not differ enough from those without DD to reflect changes in the biochemical markers of type III and I collagen.

Myocardial oxygen consumption is unchanged but efficiency is reduced in patients with essential hypertension and left ventricular hypertrophy.

BACKGROUND: Patients with hypertension and left ventricular hypertrophy (LVH) are prone to develop heart failure. We tested the hypothesis that compensatory LVH is associated with normalization of myocardial oxygen consumption and that this occurs at the expense of a decrease in the ratio between cardiac work and oxygen consumption (efficiency). METHODS AND RESULTS: Nine hypertensive men with LVH (LVH+) (age 42+/-2 years), left ventricular mass index (LVMI) 161+/-8 g/m(2), blood pressure (BP) 145+/-16/88+/-10 mm Hg (mean+/-SD); 8 hypertensive men without LVH (LVH-) (age 39+/-5 years, LVMI 107+/-15 g/m(2), BP 140+/-15/90+/-11 mm Hg); and 10 normotensive men (CONT) were studied. Myocardial blood flow, oxygen consumption, and glucose uptake were measured during euglycemic hyperinsulinemia using PET techniques. LV dimensions, volumes, and workload were determined by echocardiography, and efficiency was calculated. Myocardial workload (2.5+/-0.8 versus 3.0+/-0.6 versus 2. 3+/-0.5 mm Hg. mL. min(-1). g(-1) for CONT versus LVH- versus LVH+; P<0.05, LVH- versus LVH+), myocardial blood flow (0.84+/-0.16 versus 1.06+/-0.22 versus 0.81+/-0.09 mL. g(-1). min, respectively; P<0.05, LVH- versus other groups) and oxygen consumption (0.09+/-0.02 versus 0.14+/-0.03 versus 0.11+/-0.01 ml. g(-1). min(-1), respectively; P<0. 05, LVH- versus other groups) were increased in the LVH- group. Myocardial efficiency was reduced in the LVH+ group (18.1+/-4.1% versus 15.1+/-2.3% versus 13.5+/-1.9%, respectively; P<0.05, LVH+ versus CONT). CONCLUSIONS: Myocardial oxygen consumption per unit weight is increased in hypertensive patients without LVH but is normal in those with LVH. The normalization of oxygen consumption via hypertrophy occurs at the expense of efficiency, which may predispose hypertensive patients with LVH to heart failure.

The effect of four different antihypertensive medications on cardiovascular regulation in hypertensive sleep apneic patients--assessment by spectral analysis of heart rate and blood pressure variability.

OBJECTIVE: To study the effect of antihypertensive medications on autonomic nervous system in patients with hypertension and sleep apnea syndrome using frequency domain measures of heart rate and blood pressure variabilities. METHODS: The beta-receptor blocking agent atenolol (50 mg), the calcium antagonist isradipine SRO (2.5 mg), the diuretic hydrochlorothiazide (25 mg) and the ACE inhibitor spirapril (6 mg) once daily were given in a double-blind crossover schedule for 8 weeks. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability during the spontaneous and controlled breathing tests. During orthostatic maneuver and cold pressor test the blood pressure variability analysis also was performed. RESULTS: In general, the responses of heart rate and blood pressure variabilities were abnormal in the patients with arterial hypertension and sleep apnea syndrome compared to reference data. Of the four drugs, only atenolol effected heart rate and blood pressure variabilities as it shifted the autonomic regulation to the vagal direction. Other antihypertensive drugs did not change any parameter of heart rate or blood pressure variabilities. CONCLUSION: The short-term treatment with atenolol in patients with arterial hypertension and sleep apnea syndrome is associated with normalization of autonomic nervous control judged by heart rate and blood pressure variability. Thus, beta-receptor blockade may have adjunctive beneficial effects beyond blood pressure reduction in these patients. However, the long-term effects of blood pressure reduction on autonomic nervous control remain to be studied.

Reproducibility of abnormal heart rate variability indices: the case of hypertensive sleep apnoea syndrome.

Before heart rate variability can be used as an investigational tool in the clinical setting, its reproducibility must be known. We studied heart rate variability four times during 44 weeks in 15 hypertensive patients with sleep apnoea syndrome. Time and frequency domain analytical approaches were used during the spontaneous and controlled breathing tests, orthostatic manoeuvre and the cold pressor test. Alterations in resting heart rate were taken into account using the coefficient of component variance. In general, the response of heart rate variability was abnormal and variability was reduced in the hypertensive patients with sleep apnoea syndrome compared with reference data. Time domain measures of heart rate variability demonstrated generally better reproducibility over four recordings than frequency domain measures in these hypertensive patients with sleep apnoea syndrome. On the other hand, the reproducibility of frequency domain measures depended on the specific conditions: during orthostatic manoeuvre and cold pressor test the best reproducibility was found using normalized units. In the reference data set, there were no significant differences between the two heart rate variability recordings during any of the autonomic nervous function tests. In this follow-up study we found that simple procedures such as the controlled breathing test show good reproducibility. More complex tests such as the orthostatic manoeuvre require special attention in order to obtain acceptable reproducibility of heart rate variability measurements. Quantitatively minor changes in the variability indices when the overall variability is reduced exert major effects on the results. Therefore we suggest that reproducibility data obtained in healthy volunteers are not valid for the interpretation of data in patients with damaged cardiovascular autonomic control.