Essential hypertension

Essential hypertension can be defined as a rise in blood pressure of unknown cause that increases risk for cerebral, cardiac, and renal events. In industrialised countries, the risk of becoming hypertensive (blood pressure >140/90 mm Hg) during a lifetime exceeds 90%. Essential hypertension usually clusters with other cardiovascular risk factors such as ageing, being overweight, insulin resistance, diabetes, and hyperlipidaemia. Subtle target-organ damage such as left-ventricular hypertrophy, microalbuminuria, and cognitive dysfunction takes place early in the course of hypertensive cardiovascular disease, although catastrophic events such as stroke, heart attack, renal failure, and dementia usually happen after long periods of uncontrolled hypertension only. All antihypertensive drugs lower blood pressure (by definition) and this decline is the best determinant of cardiovascular risk reduction. However, differences between drugs exist with respect to reduction of target-organ disease and prevention of major cardiovascular events. Most hypertensive patients need two or more drugs for blood-pressure control and concomitant statin treatment for risk factor reduction. Despite the availability of effective and safe antihypertensive drugs, hypertension and its concomitant risk factors remain uncontrolled in most patients.     

高血压患者应当实施降压联合抗动脉粥样硬化的治疗

既往的实践证明,单纯降压治疗可以比较好地解决高血压导致的心力衰竭和脑卒中;单纯降压治疗可以减少部分冠心病事件,但往往获益不足。高血压患者往往比较复杂,常合并血脂异常、年龄增加、吸烟、肥胖、高血糖、心血管病早发家族史等其他危险因素,这些危险因素协同作用加剧动脉粥样硬化的发生、发展。ASCOT-LLA研究证实,在降压治疗基础上,对血脂不高当时认为不需要治疗的水平,低密度脂蛋白胆固醇〈135 mg/dL（3.51 mmol/L）但合并多项危险因素的高血压人群,联合10 mg阿托伐他汀治疗可在单纯降压降低冠心病事件10%的基础上,使致死性冠状动脉粥样硬化性心脏病和非致死性心肌梗死风险再降低36%。     

Ambulatory Blood Pressure Monitoring in the Prediction and Prevention of Coronary Heart Disease

We reviewed studies of ambulatory blood pressure monitoring (ABPM) in patients with symptomatic coronary heart disease (CHD) or asymptomatic coronary lesions and in patients at high coronary risk, such as in the presence of hypertension. We identified ten cross-sectional and seven prospective studies in patients with CHD or coronary lesions. These studies showed that patients with CHD or coronary lesions often had nocturnal non-dipping or increased blood pressure variability, and might have increased risk of coronary events, due to either uncontrolled hypertension or treatment-induced hypotension identified by ABPM. We identified ten observational studies in hypertensive patients and normotensive subjects and five therapeutic trials in hypertension. These observational studies demonstrated that one or more ambulatory blood pressure components might provide predictive value for coronary events above and beyond clinic blood pressure. The therapeutic trials were less conclusive, but suggestive of additional value for the prevention of coronary events.     

门诊高血压病患者心血管危险分层与血压控制的研究

目的　了解门诊高血压病患者的心血管危险分层与血压控制的关系。方法 :随机入选门诊原发性高血压患者10 6例 ,使用统一的表格询问和记录相关病史和检测、检查结果 ,按中国高血压防治指南的心血管危险分层方法进行分层。据危险分层的差异进行相应的治疗 ,2个月后复诊。结果　 (1) 76 9%的男性患者有 2个和 2个以上的危险因素 ,而女性只有 5 7 4% (P <0 0 5 ) ;(2 )约 6 0 %高血压病患者心血管危险分层为高危和很高危 ,34 0 %为中危 ,7 5 %为低危。 (3)经过规则治疗后 ,高血压病患者血压下降至正常 ,收缩压从 16 3 77± 16 82mmHg下降到 134 5 6± 14 45mmHg ,舒张压从 94 5 5± 11 79mmHg下降为 81 2 0± 8 37mmHg(P <0 0 5 )。心血管危险分层很高危百分比下降 ,从 31 1%下降为 14 2 % (P <0 0 1)。低危百分比上升 ,从 7 5 %上升为 14 2 % (P <0 0 5 )。结论　对高血压病患者进行心血管危险分层有助于高血压及其并发症的防治     

Cardiovascular risk in patients receiving double therapy with false and true nonresponder hypertension

OBJECTIVE: The aim of this study was to evaluate cardiovascular risk in hypertensive patients receiving double therapy with false and true nonresponder hypertension. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 730 patients receiving double therapy with uncontrolled clinic blood pressure. Two hundred and seventy had false nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure <135/85 mmHg) and 460 had true nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure > or =135 or 85 mmHg). RESULTS: During the follow-up (4.77+/-2.9 years, range 0.2-11.7 years), 55 cardiovascular events occurred. The event rates per 100 patient-years in patients with false and true nonresponder hypertension were 1.03 and 1.9, respectively. Event-free survival was significantly different between the groups (P<0.05). After adjustment for several covariates, including clinic blood pressure (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in true than in false nonresponder hypertension (relative risk 2.33, 95% confidence interval 1.14-4.77, P=0.02). CONCLUSIONS: This study shows that, among treated hypertensive patients receiving double therapy with uncontrolled clinic blood pressure those with true nonresponder hypertension are at higher cardiovascular risk. Ambulatory blood pressure monitoring should be performed in this population to achieve a better prognostic stratification.     

Dual-Acting Angiotensin Receptor–Neprilysin Inhibition

Lowering blood pressure by pharmacologic intervention reduces the incidence of cardiovascular events. Nevertheless, despite the widespread availability of effective antihypertensive medications, the vast majority of hypertensive patients worldwide continue to have inadequate blood pressure control. The development of new antihypertensive drugs could contribute to improving the hypertension control rate, and the blockade of new pathophysiologic pathways involved in blood pressure regulation would offer additional benefits. The dual inhibition of the angiotensin II receptor and neprilysin could provide clinical benefits in a range of cardiovascular diseases, including hypertension and heart failure.     

Sympathetic activation and contribution of genetic factors in hypertension with neurovascular compression of the rostral ventrolateral medulla

OBJECTIVE: The rostral ventrolateral medulla is an important center for the regulation of sympathetic and cardiovascular activities. Reportedly, neurovascular compression of the rostral ventrolateral medulla may be causally related to essential hypertension. We aimed to determine the mechanism behind elevated blood pressure in hypertensive patients with compression of the rostral ventrolateral medulla and to investigate whether genetic factors contribute to the etiology of hypertension with compression. DESIGN AND METHODS: The study included 56 patients with essential hypertension and 25 normotensive individuals. With the use of magnetic resonance imaging, the essential hypertension group was subdivided into hypertension with compression and without compression groups. We compared plasma levels of hormones that raise blood pressure and family histories of hypertension between the two hypertension groups and the normotension group. RESULTS: Plasma norepinephrine levels, but not plasma renin activity, aldosterone, epinephrine, or vasopressin levels, were significantly higher in the hypertension with compression group (389+/-53 pg/ml) than in the hypertension without compression group (217+/-38, P<0.05) or in the normotension group (225+/-30, P<0.05). The percentage of individuals who had two hypertensive parents was significantly higher in the hypertension with compression group (39.4%) than in the hypertension without compression group (13.0%, P<0.05) or in the normotension group (8.0%, P<0.01). CONCLUSIONS: These results indicate that neurovascular compression of the rostral ventrolateral medulla might be, at least in part, causally related to essential hypertension by increasing sympathetic nerve activity. They also suggest that genetic factors might contribute to the etiology of hypertension with neurovascular compression.     

The Renin-Angiotensin System in Essential Hypertension: Associations with Cardiovascular Risk

The importance of the renin-angiotensin system (RAS) in blood pressure regulation is well established. High RAS activity has also been implicated in connection with elevated cardiovascular risk in patients with essential hypertension. Data from epidemiological studies have related high plasma renin levels in essential hypertensive patients to cardiovascular complications. However, whether renin itself is a risk factor of cardiovascular events or just acts as a marker for other risk factors still remains to be elucidated. Several possible mechanisms that could be responsible for the association between elevated RAS activity and cardiovascular risk are reviewed. The concept of high RAS activity being a cardiovascular risk factor is strongly supported by results from large clinical studies showing the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in congestive heart failure and hypertension. Knowing more about the exact mechanisms of the association between high RAS activity and cardiovascular complications would enable us to profile the treatment of high blood pressure more specifically to improve outcome in individuals or groups of patients.     

Association between hypertensive urgencies and subsequent cardiovascular events in patients with hypertension

OBJECTIVE: To determine whether patients with hypertensive urgency have a higher risk for subsequent cardiovascular events compared with hypertensive patients without this event. METHODS: Overall, 384 patients with hypertensive urgency and 295 control patients were followed up for at least 2 years. Hypertensive urgency was defined as a systolic blood pressure above 220 mmHg and/or a diastolic blood pressure above 120 mmHg without any evidence of acute end-organ damage. The control group consisted of patients admitted to the emergency department with a systolic blood pressure between 135 to 180 mmHg and a diastolic blood pressure between 85-110 mmHg. The number of cardiovascular events defined as acute coronary syndrome, acute stroke, atrial fibrillation, acute left ventricular failure and aortic aneurysm were consecutively analyzed during follow-up. The median follow-up time was 4.2 years (interquartile range 2.9-5.7 years). Twenty-six patients of the urgency group and 23 patients of the control group were lost for follow-up. RESULTS: Overall, 117 (17%) patients had nonfatal clinical cardiovascular events and 13 had (2%) fatal cardiovascular events. The frequency of cardiovascular events was significantly higher in patients with hypertensive urgencies (88 vs. 42; P = 0.005). The Cox regression analysis identified age (P < 0.001) and hypertensive urgencies (P = 0.035) as independent predictors for subsequent cardiovascular events. CONCLUSIONS: Hypertensive urgencies are associated with an increased risk for subsequent cardiovascular events in patients with arterial hypertension.     

Blood pressure parameters and cardiovascular risk in the elderly

The treatment decision must take into account the benefit and risks related to the intervention: the benefit demonstrated and quantified in many therapeutic trials in hypertension in the elderly, but also the patient's initial risk. It is now recognized that, in elderly hypertensive patients, systolic blood pressure is a better predictor of morbid and lethal events related to hypertension than diastolic blood pressure. Recent data in the medical literature attribute a predictive role to pulse pressure which is even greater than that of systolic blood pressure. From a pathophysiological point of view, the level of pulse pressure reflects the degree of rigidity of large arterial trunks. The arterial rigidity parameter could integrate the harmful effect of "cardiovascular risk factors" (hypertension, but also atherogenic dyslipidaemia, diabetes, smoking, homocysteine, genetic factors, etc.) on the years or decades of exposure, and pulsed pressure would therefore appear to be a better marker of cardiovascular risk than other blood pressure parameters. Pulse pressure should therefore be integrated into the benefit/risk ratio of antihypertensive treatment in the elderly.     

Total Cardiovascular Risk, Blood Pressure Variability and Adrenergic Overdrive in Hypertension: Evidence, Mechanisms and Clinical Implications

In hypertensive patients the risk of developing cardiovascular events and complications depends not only on the magnitude of the blood pressure elevation, but also, and to a consistent extent, on the presence of associated cardiovascular risk factors, concomitant disease and target organ damage. Recent findings suggest that also sympathetic overdrive and alterations in blood pressure variability (which are detected in hypertension) may participate at the increased cardiovascular risk of the patients with high blood pressure. This review will discuss the evidence collected over the past few years on the relationships between sympathetic activation and blood pressure variability and their impact on cardiovascular risk profile.     

Epidemiologic appraisal of hypertension as a coronary risk factor in the elderly

Five decades of epidemiologic research has established elevated blood pressure as a major contributor to atherosclerotic cardiovascular diseases in the elderly, including coronary heart disease. Clinicians formerly favored the diagnosis and treatment of hypertension in terms of the diastolic blood pressure and categorical "hypertension." Epidemiologic data now emphasize the essential role of systolic blood pressure, pulse pressure, and a graded influence of blood pressure, even within the high-normal range. The risk of coronary heart disease, the most common lethal sequela of hypertension, increases with the extent of risk factor clustering. Among hypertensive persons, about 39% of coronary events in men and 68% in women are attributable to the presence of two or more additional risk factors. When risk factor clustering is associated with glucose intolerance, obesity, and dyslipidemia, it may be attributed to insulin resistance promoted by abdominal obesity. Other hazardous influences often accompanying hypertension in the elderly are the presence of an elevated heart rate, elevated levels of fibrinogen, and left ventricular hypertrophy. Because clustering with other risk factors is characteristic of hypertension in the elderly, it is essential to screen for them and for the presence of comorbid cardiovascular diseases, target organ disease, and subclinical vascular disease likely to be present. Multivariate risk assessment profiles enable global estimation of hypertensive risk of developing coronary heart disease. Hypertensive elderly patients are more appropriately targeted for antihypertensive therapy by such risk stratification than by relying solely on the severity of the blood pressure elevation. The goal of therapy should be to improve the multivariate risk profile as well as the level of the blood pressure.     

High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal?

OBJECTIVE: To analyze the available data to assess the benefits of antihypertensive therapy in hypertensive patients with diabetes mellitus. METHODS: A MEDLINE search of English-language articles published until June 1999 was undertaken with the use of the terms diabetes mellitus, hypertension or blood pressure, and therapy. Pertinent articles cited in the identified reports were also reviewed. Included were only prospective randomized studies of more than 12 months' duration that evaluated the effect of drug treatment on morbidity and mortality in diabetic hypertensive patients. We estimated the risk associated with combination of diabetes mellitus and hypertension and the effect of treatment on morbidity and mortality. RESULTS: The coexistence of diabetes mellitus doubled the risk of cardiovascular events, cardiovascular mortality, and total mortality in hypertensive patients (approximate relative risk of 1.73-2.77 for cardiovascular events, 2.25-3.66 for cardiovascular mortality, and 1.73-2.18 for total mortality). Intensive blood pressure control to levels lower than 130/85 mm Hg was beneficial in diabetic hypertensive patients. All 4 drug classes-diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists-were effective in reducing cardiovascular events in diabetic hypertensive patients. In elderly diabetic patients with isolated systolic hypertension, calcium antagonists reduced the rate of cardiac end points by 63%, stroke by 73%, and total mortality by 55%. In more than 60% of diabetic hypertensive patients, combination therapy was required to control blood pressure. CONCLUSIONS: Intensive control of blood pressure reduced cardiovascular morbidity and mortality in diabetic patients regardless of whether low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists were used as a first-line treatment. A combination of more than 1 drug is frequently required to control blood pressure and may be more beneficial than monotherapy.     

The relationship between inflammation and arterial stiffness in patients with essential hypertension

BACKGROUND: Data about the correlation between augmentation index (AIx), timing of the reflected waveform (T(r)) and inflammatory markers in patients with essential hypertension are not yet well established. The aim of this study was to compare plasma high-sensitivity C-reactive protein (hsCRP), white blood cell count and fibrinogen in hypertensive patients and in normotensive controls and to assess the relationship between inflammatory markers and arterial stiffness. METHODS: Forty-two healthy middle-aged patients with untreated stage I-II essential hypertension and 42 sex- and age-matched controls were recruited in the study. Pulse wave analysis was used to assess AIx and T(r). RESULTS: Plasma hsCRP, white blood cell count, AIx and T(r) were significantly higher in the patients with essential hypertension. In multiple regression analysis, AIx correlated positively with age, female gender, mean arterial pressure and log(hsCRP), and negatively with heart rate and height (R(2)=0.75, p<0.001). T(r) correlated negatively with log(hsCRP) (r=-0.34, p=0.002) for the whole study group. However, after adjusting for mean arterial pressure, age, height, heart rate and sex to the regression model, no correlation was revealed between log(hsCRP) and T(r) (p=0.35) as the dependent variable (R(2)=0.48, p<0.001). CONCLUSIONS: Untreated hypertensive patients with low or moderate total cardiovascular risk had significantly increased blood hsCRP and white blood cell count and arterial stiffness, expressed as AIx and T(r). AIx correlated independently with hsCRP in multiple regression analysis. Measurement of arterial stiffness and inflammation can be suggested as an additional tool to assess cardiovascular risk in hypertensive patients with low or moderate total cardiovascular risk as estimated by traditional risk factors.     

Dietary risk markers that contribute to the aetiology of hypertension in black South African children: the THUSA BANA study

Although clinical hypertension occurs less frequently in children than in adults, ample evidence supports the concept that the roots of essential hypertension extend back to childhood. Since little is available in the literature on causal dietary factors of hypertension in children, this study hypothesised that certain dietary factors can be identified as risk markers that might contribute to the aetiology of hypertension in black children. Children aged 10-15 years were randomly selected from 30 schools in the North West Province from 2000 to 2001. These children comprised 321 black males and 373 females from rural to urbanised communities, of which 40 male and 79 female subjects were identified with high-normal to hypertensive blood pressure. Blood pressure was measured with a Finapres apparatus and data were analysed with the Fast Modelflo software program to provide systolic, diastolic and mean blood pressure. A 24-h dietary recall questionnaire and weight and height measurements were taken. In a stepwise regression analysis, the following variables were significantly associated (P < or = 0.05) with blood pressure parameters of hypertensive males: biotin, folic acid, pantothenic acid, zinc and magnesium. Energy, biotin and vitamin A intakes were significantly associated with blood pressure parameters of hypertensive females. No significant dietary markers were indicated for any of the normotensive groups. Dietary intakes of all of these nutrients were well below the dietary reference intakes. In conclusion, the dietary results coupled with the cardiovascular parameters of this study identified folic acid and biotin as risk markers that could contribute to the aetiology of hypertension in black persons. The low intakes of these nutrients, among others, is a matter of serious concern, as is the increasing tendency towards urbanisation.     

Sex‐Specific Differences in Cardiovascular Risk Factors and Blood Pressure Control in Hypertensive Patients

Cardiovascular disease (CVD) and cardiovascular risk factors are frequently undertreated in women. However, it is unclear whether the prevalence of additional cardiovascular risk factors and the total cardiovascular risk differ between hypertensive men and women. There are also limited data regarding rates of blood pressure control in the two sexes outside the United States. The authors aimed to compare the cardiovascular risk profile between sexes. A total of 1810 hypertensive patients (40.4% men, age 56.5±13.5 years) attending the hypertension outpatient clinic of our department were studied. Men were more frequently smokers than women and were more heavy smokers than the latter. Serum high‐density lipoprotein cholesterol levels were lower and serum triglyceride levels were higher in men. On the other hand, abdominal obesity and chronic kidney disease were more prevalent in women. The estimated cardiovascular risk was higher in men than in women but the prevalence of established CVD did not differ between the sexes. The percentage of patients with controlled hypertension and the number of antihypertensive medications were similar in men and women. In conclusion, hypertensive men have more adverse cardiovascular risk factor profile and greater estimated cardiovascular risk than women. However, the prevalence of established CVD does not differ between sexes. These findings further reinforce current guidelines that recommend that management of hypertension and of other cardiovascular risk factors should be as aggressive in women as in men in order to prevent cardiovascular events.     

Estimated prevalence of uncontrolled hypertension and multiple cardiovascular risk factors and their associated risk of coronary heart disease in the United States

This study determined the prevalence of primary prevention patients aged 40 to 79 years with uncontrolled hypertension (HTN) and low/moderate cholesterol levels, and the clinical and economic consequences of their cardiovascular risk levels stratified by additional cardiovascular risk factors. Prevalence was estimated from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES) datasets. Framingham risk equations were used to calculate the 4-year risk of coronary heart disease (CHD). HTN and cholesterol levels were then statistically “controlled” to ideal levels and risks were recalculated. Prevalence of uncontrolled hypertension was 15.2 million cases (13.7%). Of those, 12.9 million (84.8%) had low/moderate cholesterol levels, and 2.2 million (16.7%) had ≥3 additional risk factors with no history of CHD. Nearly 200,000 coronary events are expected to occur within 4 years, incurring over $2.5 billion in direct medical costs. Statistical estimation suggests that 64% of 4-year risk was attributable to uncontrolled blood pressure and lipids. The large number and high cost of CHD events expected to occur within the next 4 years in primary prevention patients with uncontrolled hypertension and ≥3 additional risk factors justifies aggressive screening to ensure that these patients are identified and properly managed.     

Why is blood pressure so hard to control in patients with type 2 diabetes?

Resistance to antihypertensive drugs is common in hypertensive patients with type 2 diabetes. This is unfortunate because hypertension is one of the most important risk factors for development of cardiovascular events, and the goal blood pressure level is set lower in diabetic subjects than in nondiabetic subjects. Previous outcome trials in diabetic subjects have mainly focused on end points such as microalbuminuria or the incidence of cardiovascular events rather than on reduction of blood pressure; some reports, however, have suggested mechanisms for the drug resistance. These include several clinical conditions known to be associated with difficulty in reducing blood pressure specifically in diabetes mellitus: change in the renin-angiotensin system and chymase, volume overload, central sympathetic hyperactivity, sleep apnea, secondary hypertension, pseudoresistance (white coat hypertension), and poor compliance related to subclinical depression. In this review, the authors focus on the mechanisms of resistance to antihypertensive therapy (particularly for monotherapy with either angiotensin-converting enzyme inhibitors or angiotensin II antagonists) in the treatment of diabetic hypertension.     

Statins and blood pressure regulation

Hypertension and high serum cholesterol levels are two of the most relevant risk factors for cardiovascular diseases. A combined increase in both risk factors has been reported in a significant proportion of patients with coronary artery disease. Statins are the most widely used drugs to treat hypercholesterolemia, and they interact with blood pressure control in different populations of hypertensive patients. A significant reduction in blood pressure associated with the use of statins has been described in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin converting enzyme inhibitors and calcium channel blockers. The effect of statins on blood pressure control has also been reported in diabetic patients. The mechanisms responsible for the hypotensive effect seem to be largely independent of the effect of statins on lipid profile, and are probably related to their interaction with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control could be a useful consideration for an integrated approach to better prevention of cardiovascular diseases.     

Elevated systolic blood pressure as a cardiovascular risk factor

This paper reviews the evolution of attitudes toward the treatment and diagnosis of hypertension. In particular, there is a growing realization that elevated systolic pressure may be a more valuable measurement in evaluating and controlling hypertension than is generally acknowledged. A large number of epidemiologic studies in a wide variety of populations have revealed that systolic blood pressure exerts a stronger influence than diastolic blood pressure. The largest of these, the Framingham Heart Study, showed that in subjects with systolic hypertension, diastolic blood pressure was only weakly related to the risk of cardiovascular events, but in those with diastolic hypertension, the risk of these events was strongly influenced by the level of systolic pressure. Furthermore, cardiovascular event rates were found to increase steeply with systolic pressure and were higher in cases of isolated systolic hypertension than diastolic hypertension. Clinical trials produced similar results, again suggesting that a greater reliance should be placed on systolic pressure in evaluating the risk of cardiovascular problems. This review concludes that the health community needs to be reeducated to consider the importance of systolic and diastolic blood pressure in assessing appropriate management strategies for hypertensive patients.