Luiz Aparecido Bortolotto

Obstructive Sleep Apnea The Most Common Secondary Cause of Hypertension Associated With Resistant Hypertension

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9–14.2]; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio: 4.7 [95% CI: 1.3–16.9]; P=0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3–11]; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension

Exercise is an effective intervention for treating hypertension and arterial stiffness, but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects. Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients. Sixty-five patients with hypertension were randomized to 16 weeks of continuous exercise training (n=26), interval training (n=26) or a sedentary routine (n=13). The training was conducted in two 40-min sessions a week. Assessment of arterial stiffness by carotid–femoral pulse wave velocity (PWV) measurement and 24-h ambulatory blood pressure monitoring (ABPM) were performed before and after the 16 weeks of training. At the end of the study, ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality. PWV had declined significantly only after interval training from 9.44±0.91 to 8.90±0.96 m s−1, P=0.009 (continuous from 10.15±1.66 to 9.98±1.81 m s−1, P=ns; control from 10.23±1.82 to 10.53±1.97 m s−1, P=ns). Continuous and interval exercise training were beneficial for blood pressure control, but only interval training reduced arterial stiffness in treated hypertensive subjects.

Additive Effects of Obstructive Sleep Apnea and Hypertension on Early Markers of Carotid Atherosclerosis

Obstructive sleep apnea (OSA) has emerged as an independent risk factor for atherosclerosis. However, OSA is frequently associated with several risk factors for atherosclerosis, including hypertension (HTN). The impact of OSA and HTN alone compared with the association of both conditions on carotid atherosclerosis is not understood. We studied 94 middle-aged participants free of smoking and diabetes mellitus who were divided into 4 groups: controls (n=22), OSA (n=25), HTN (n=20), and OSA+HTN (n=27). All of the participants underwent polysomnography and carotid measurements of intima-media thickness, diameter, and distensibility with an echo-tracking device. Compared with controls, intima-media thickness and carotid diameter were similarly higher in OSA (713±117 and 7117±805 &mgr;m), and HTN groups (713±182 and 7191±818 &mgr;m), with a further significant increase in OSA+HTN patients (837±181 and 7927±821 &mgr;m, respectively; P<0.01). Carotid distensibility was significantly lower in HTN (P<0.05) and OSA+HTN subjects (P<0.001) compared with controls. In the OSA+HTN group, carotid distensibility was significantly lower than in the OSA group and controls (P<0.05 for each comparison). Multivariate analysis showed that intima-media thickness was positively related to systolic blood pressure and apnea-hypopnea index. Apnea-hypopnea index was the only factor related to carotid diameter. Age and systolic blood pressure were independently related to carotid distensibility. In conclusion, the association of OSA and HTN has additive effects on markers of carotid atherosclerosis. Because early markers of carotid atherosclerosis predict future cardiovascular events, including not only stroke but also myocardial infarction, these findings may help to explain the increased risk of cardiovascular disease in patients with OSA.

Effects of high-intensity aerobic interval training vs. moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension

Exercise training has an important role in the prevention and treatment of hypertension, but its effects on the early metabolic and hemodynamic abnormalities observed in normotensive offspring of hypertensive parents (FH+) have not been studied. We compared high-intensity interval (aerobic interval training, AIT) and moderate-intensity continuous exercise training (CMT) with regard to hemodynamic, metabolic and hormonal variables in FH+ subjects. Forty-four healthy FH+ women (25.0±4.4 years) randomized to control (ConFH+) or to a three times per week equal-volume AIT (80–90% of VO2MAX) or CMT (50–60% of VO2MAX) regimen, and 15 healthy women with normotensive parents (ConFH−; 25.3±3.1 years) had their hemodynamic, metabolic and hormonal variables analyzed at baseline and after 16 weeks of follow-up. Ambulatorial blood pressure (ABP), glucose and cholesterol levels were similar among all groups, but the FH+ groups showed higher insulin, insulin sensitivity, carotid-femoral pulse wave velocity (PWV), norepinephrine and endothelin-1 (ET-1) levels and lower nitrite/nitrate (NOx) levels than ConFH− subjects. AIT and CMT were equally effective in improving ABP (P<0.05), insulin and insulin sensitivity (P<0.001); however, AIT was superior in improving cardiorespiratory fitness (15 vs. 8%; P<0.05), PWV (P<0.01), and BP, norepinephrine, ET-1 and NOx response to exercise (P<0.05). Exercise intensity was an important factor in improving cardiorespiratory fitness and reversing hemodynamic, metabolic and hormonal alterations involved in the pathophysiology of hypertension. These findings may have important implications for the exercise training programs used for the prevention of inherited hypertensive disorder.

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

OBJECTIVE Metabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS. METHODS Eighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) > or =15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters. RESULTS Fifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS-OSA). Compared with MS-OSA patients, MS+OSA patients had higher levels of IMT (661+/-117 vs. 767+/-140 microm), PWV (9.6+/-1.0 vs. 10.6+/-1.6m/s), and CD (6705+/-744 vs. 7811+/-862 microm) (P<0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R(2)=0.42); AHI and systolic blood pressure (R(2)=0.38); and AHI, age, abdominal circumference and systolic blood pressure (R(2)=0.45), respectively. The R(2) of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively. CONCLUSIONS OSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.

Effects of OSA Treatment on BP in Patients With Resistant Hypertension: A Randomized Trial

BACKGROUND OSA is extremely common among patients with resistant hypertension (HTN). However, the impact of the treatment of OSA with CPAP on BP in patients with resistant HTN is not well established. METHODS In the current study, 40 patients with confirmed resistant HTN and moderate to severe OSA confirmed by full polysomnography were randomized to medical therapy or to medical treatment plus CPAP for 6 months. Patients were evaluated at study baseline and after 6 months by 24-h ambulatory BP monitoring (ABPM). RESULTS Thirty-five patients (77% men; age, 56 ± 1 years; BMI, median 32 kg/m² [25%-75%, 28-39 kg/m²]; apnea-hypopnea index, 29 events/h [24-48 events/h]; Epworth Sleepiness Scale, 10 ± 1; systolic/diastolic office BP, 162 ± 4/97 ± 2 mm Hg; taking four [four to five] antihypertensive drugs) completed the study. CPAP was used for 6:01 ± 0:20 h/night (3:42-7:44 h/night). Compared with the control group, awake systolic/diastolic ABPM decreased significantly in the CPAP group (Δ: +3.1 ± 3.3 /+2.1 ± 2.7 mm Hg vs -6.5 ± 3.3/-4.5 ± 1.9 mm Hg, respectively, P < .05). Interestingly, the BP changes were observed only while patients were awake, but not during nocturnal ABPM (Δ: +2.8 ± 4.5/+1.8 ± 3.5 mm Hg vs +1.6 ± 3.5/+0.8 ± 2.9 mm Hg, P = NS). CONCLUSIONS The treatment of OSA with CPAP significantly reduces daytime BP in patients with resistant HTN. Therefore, our study reinforces the importance of recognizing and treating OSA in patients with resistant HTN. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00812695; URL: www.clinicaltrials.gov.

Acute effects of continuous and interval aerobic exercise on 24-h ambulatory blood pressure in long-term treated hypertensive patients.

BACKGROUND Despite antihypertensive therapy, it is difficult to maintain optimal systemic blood pressure (BP) values in hypertensive patients (HPT). Exercise may reduce BP in untreated HPT. However, evidence regarding its effect in long-term antihypertensive therapy is lacking. Our purpose was to evaluate the acute effects of 40-minute continuous (CE) or interval exercise (IE) using cycle ergometers on BP in long-term treated HPT. METHODS Fifty-two treated HPT were randomized to CE (n=26) or IE (n=26) protocols. CE was performed at 60% of reserve heart rate (HR). IE alternated consecutively 2 min at 50% reserve HR with 1 min at 80%. Two 24-h ambulatory BP monitoring were made after exercise (postexercise) or a nonexercise control period (control) in random order. RESULTS CE reduced mean 24-h systolic (S) BP (2.6+/-6.6 mm Hg, p=0.05) and diastolic (D) BP (2.3+/-4.6, p=0.01), and nighttime SBP (4.8+/-6.4, p<0.001) and DBP (4.6+/-5.2 mm Hg, p=0.001). IE reduced 24-h SBP (2.8+/-6.5, p=0.03) and nighttime SBP (3.4+/-7.2, p=0.02), and tended to reduce nighttime DBP (p=0.06). Greater reductions occurred in higher BP levels. Percentage of normal ambulatory BP values increased after CE (24-h: 42% to 54%; daytime: 42% to 61%; nighttime: 61% to 69%) and IE (24-h: 31% to 46%; daytime: 54% to 61%; nighttime: 46% to 69%). CONCLUSION CE and IE reduced ambulatory BP in treated HPT, increasing the number of patients reaching normal ambulatory BP values. These effects suggest that continuous and interval aerobic exercise may have a role in BP management in treated HPT.

Obstructive sleep apnea, masked hypertension, and arterial stiffness in men.

BACKGROUND Obstructive sleep apnea (OSA) is an established cause of hypertension. However, it is not clear whether the frequency of masked hypertension in patients with OSA and whether OSA have an independent role on arterial stiffness taking into account ambulatory blood pressure (BP) monitoring (ABPM). METHODS We evaluated 61 male normotensive participants as determined by casual clinic BP level <140/90 mm Hg without clinical evidence of cardiovascular disease and on no medications (43 patients with moderate-to-severe OSA (apnea-hypopnea index (AHI) > or = 15 events/hour by polysomnography) and 18 age- and body mass index-matched controls without OSA (AHI <5 events/hour)). Pulse wave velocity (PWV), an index of arterial stiffness, and 24-h ABPM were performed in a blinded fashion. Masked hypertension was defined when abnormal daytime ABPM was > or = 135 or > or = 85 mm Hg. RESULTS The AHI and lowest oxygen saturation were 2.6 +/- 1.6 and 90 +/- 2 vs. 52.8 +/- 21.0 events/hour and 75 +/- 10% for controls and OSA patients, respectively; P < 0.001. Compared with controls, patients with OSA had higher office systolic BP (113 +/- 9 vs. 118 +/- 10 mm Hg; P = 0.05) and a higher unadjusted proportion of masked hypertension (2 controls (11.1%) vs. 13 patients (30.2%); P < 0.05). PWV was 8.7 +/- 0.7, 9.4 +/- 1.0, and 10.6 +/- 1.1 m/s in the control, OSA without and with masked hypertension groups, respectively (P < 0.01 for each comparison). Multiple regression showed that systolic daytime ABPM and the lowest oxygen saturation were independently related to PWV (adjusted R2 = 0.34; P < 0.01). CONCLUSIONS Patients with OSA presented a higher unadjusted rate of masked hypertension than matched controls. Lowest oxygen saturation has an independent association with arterial stiffness.

Acute aerobic exercise reduces 24-h ambulatory blood pressure levels in long-term-treated hypertensive patients

BACKGROUND Even with anti-hypertensive therapy, it is difficult to maintain optimal systemic blood pressure values in hypertensive patients. Exercise may reduce blood pressure in untreated hypertensive, but its effect when combined with long-term anti-hypertensive therapy remains unclear. Our purpose was to evaluate the acute effects of a single session of aerobic exercise on the blood pressure of long-term-treated hypertensive patients. METHODS Fifty treated hypertensive patients (18/32 male/female; 46.5±8.2 years; Body mass index: 27.8±4.7 kg/m2) were monitored for 24 h with respect to ambulatory (A) blood pressure after an aerobic exercise session (post-exercise) and a control period (control) in random order. Aerobic exercise consisted of 40 minutes on a cycle-ergometer, with the mean exercise intensity at 60% of the patient’s reserve heart rate. RESULTS Post-exercise ambulatory blood pressure was reduced for 24 h systolic (126±8.6 vs. 123.1±8.7 mmHg, p=0.004) and diastolic blood pressure (81.9±8 vs. 79.8±8.5 mmHg, p=0.004), daytime diastolic blood pressure (85.5±8.5 vs. 83.9±8.8 mmHg, p=0.04), and nighttime S (116.8±9.9 vs. 112.5±9.2 mmHg, p<0.001) and diastolic blood pressure (73.5±8.8 vs. 70.1±8.4 mmHg, p<0.001). Post-exercise daytime systolic blood pressure also tended to be reduced (129.8±9.3 vs. 127.8±9.4 mmHg, p=0.06). These post-exercise decreases in ambulatory blood pressure increased the percentage of patients displaying normal 24h systolic blood pressure (58% vs. 76%, p=0.007), daytime systolic blood pressure (68% vs. 82%, p=0.02), and nighttime diastolic blood pressure (56% vs. 72%, p=0.02). Nighttime systolic blood pressure also tended to increase (58% vs. 80%, p=0.058). CONCLUSION A single bout of aerobic exercise reduced 24h ambulatory blood pressure levels in long-term-treated hypertensive patients and increased the percentage of patients reaching normal ambulatory blood pressure values. These effects suggest that aerobic exercise may have a potential role in blood pressure management of long-term-treated hypertensive.

Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

BACKGROUND Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). OBJECTIVE Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. METHODS 102 FH subjects (36% male, 45 ± 13 years, LDL-c 280 ± 54 mg/dL) and 35 controls (40% male, 46 ± 12 years, LDL-c 103 ± 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. RESULTS FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p=0.0005), stenosis (19% vs. 3%, p=0.015), segments with plaques (2.05 ± 2.85 vs.0.43 ± 1.33, p=0.0016) and calcium scores (55 ± 129 vs. 38 ± 140, p=0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR=2.06, for age change of 10 years, CI95%: 1.38-3.07, p<0.001) and total cholesterol (OR=1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p=0.027). Coronary calcium score was associated with the presence of stenosis (OR=1.54; CI95%: 1.27-1.86, p<0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p=0.014) and inversely with calcified plaques (OR=0.21, CI95%: 0.05-0.84, p=0.027). Family history of early CHD was associated with the presence of mixed plaques (OR=4.90, CI95%: 1.32-18.21, p=0.018). CONCLUSIONS Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population.