Asymptomatic Hypertension Research Articles

Early atherosclerosis in human hypertension.

The detection of preclinical atherosclerosis may contribute to better identifying hypertensive subjects at high risk of complications. Three alterations can be diagnosed noninvasively: calcification, thickening, and stiffening of the arterial wall. Their prevalence is increased in asymptomatic hypertensives and their presence may have important prognostic significance, especially with respect to coronary artery disease. They are also ideal targets to test the efficacy of hypertensive therapy on the arterial wall. Finally, the detection of early atherosclerosis may help to improve the clinical management of hypertensive patients.

First-Degree Kinship with Young Coronary Artery Disease Patients Markedly Increases Lipid-Level Disorders in Asymptomatic Hypertensives

Association of hypertension and serum lipid disorders has been demonstrated in previous studies. However, there are no investigations about the behaviour of serum lipids in asymptomatic hypertensive individuals who are first degree relatives of young coronary patients. To determine the degree of lipid disorders in Brazilian hypertensive individuals who are first degree relatives of young coronary patients. There were four study groups, 2 in each arm of the study: a) 846 subjects without any evidence of heart disease or diabetes who were first degree relatives of patients who underwent coronary artery bypass grafting (CABG) surgery before 55 years-of-age. Of these subjects, 226 individuals were hypertensive (group Hyp F), and 620 were normotensive (group Normo F): b) 910 hospital employees without evidence of cardiovascular disease and family history of coronary artery disease of whom 152 were hypertensive (group Hyp NF), and 758 were normotensive (group Normo NF). Hypertension was defined as blood pressure greater than 140/90 mmHg. The following serum lipid measurements were performed: total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprtein cholesterol (LDLC), and triglycerides. Lipid disorders were defined according to the 2nd Report of the National Cholesterol Education Program (NCEP) (total cholesterol>240 mg/dl; LDLC>160 mg/dl; triglycerides>200 mg/dl). The frequency of lipid disorders in each group was calculated. Subjects were classified according to their body mass index (BMI) as normal, overweight, or obese. The following statistical analyses were performed as indicated: ANOVA (with Tukey's corrections for multiple comparisons), chi-square (x2), and odds ratio (OR). Hyp F subjects had significantly higher total cholesterol, LDLC and triglyceride levels, and significantly lower levels of HDLC than all other groups. There was a higher frequency of lipid disorders in Hyp F subjects than in Hyp NF individuals, with a significant OR of 1.71 (CI 1.26-2.32) and 2.09 (CI 1.48-2.72) for total cholesterol and LDLC respectively. When compared to Normo F subjects, Hyp F individuals had significantly higher risk of having lipid disorders: total cholesterol (OR=8), LDLC (OR=6), and triglycerides (OR=5). There was a higher frequency of obesity among Hyp F patients than in all other groups. The frequency of subjects who were overweight or obese was higher in Hyp F than in Hyp NF subjects. Hypertensive patients who were first degree relatives of patients revascularized at a young age had a higher prevalence of lipid disorders, particularly higher total cholesterol and LDLC, than hypertensive individuals without this family history. These individuals may have a greater genetic propensity to develop lipid disorders.

First-degree kinship with young coronary artery disease patients markedly increases lipid-level disorders in asymptomatic hypertensives

First-degree kinship with young coronary artery disease patients markedly increases lipid-level disorders in asymptomatic hypertensives

Emergency Department Hypertension and Regression to the Mean

Study objective: To evaluate the importance of regression to the mean in the assessment of asymptomatic hypertension in the emergency department. Methods: This was an historical cohort study of patients in the adult ED of a large urban teaching hospital. The main outcome was change in diastolic blood pressure (DBP). Subjects were 195 consecutive hypertensive patients with two sets of vital signs. Patients with specified acute conditions potentially associated with abnormal blood pressure were excluded, as were patients given vasoactive medications. Results: A statistical formula was used to predict the average blood pressure for hypertensive patients, using the observed mean and standard deviation of an all-patient sample. Given a threshold of 90 mm Hg, the expected mean DBP for hypertensive patients was 102.7 mm Hg, compared with an observed value of 104.5 mm Hg. Given an observed correlation coefficient of .73 between first and second measurements, a formula for regression to the mean predicted a spontaneous blood pressure decline of 7.2 mm Hg. A mean decline of 11.6 mm Hg was observed. The decline of 4.4 mm Hg more than expected among asymptomatic hypertensives was similar to the spontaneous decline of 3.7 mm Hg observed in the all-patient sample. Conclusion: Patients who present with asymptomatic hypertension in the ED on average experience a spontaneous decline in blood pressure after they arrive. Most of this effect can be explained by regression to the mean. A small amount of this drop may represent attenuation of an initial alerting reaction. [Pitts SR, Adams RP: Emergency department hypertension and regression to the mean. Ann Emerg Med February 1998;31:214-218.]

After Successful Endarterectomy for Symptomatic Carotid Stenosis, Should Any Contralateral but Asymptomatic Carotid Stenosis Be Operated on as Well?

We sought to determine whether there are any subgroups of patients who might benefit from endarterectomy of the asymptomatic carotid artery after successful operation for a symptomatic carotid stenosis. The incidence and outcome of stroke in the asymptomatic carotid artery distribution was prospectively studied in 966 patients who were entered into the European Carotid Surgery Trial and had a 30–99% asymptomatic carotid stenosis. The patients had been randomized to either carotid endarterectomy (61%) or no endarterectomy of their symptomatic carotid stenosis. We reviewed the literature on the risks and efficacy of carotid endarterectomy and used these data in a decision analysis. The 5-year risk of stroke lasting more than 7 days in the asymptomatic carotid distribution was 3.4%. Two independent prognostic factors were identified by means of Cox''s proportional hazards regression with stepwise forward selection: the degree of asymptomatic carotid stenosis (30–69 vs. 70–99%) and hypertension. The 5-year-restricted and quality-adjusted life expectancy for a patient with both a severe (70–99%) asymptomatic carotid stenosis and hypertension, and therefore with the highest risk of asymptomatic carotid distribution stroke, was 4.14 life years for both conservative management and for endarterectomy. Plausible changes in the estimated risk of asymptomatic carotid distribution stroke, and in the rate of complications from endarterectomy, increased the benefit of endarterectomy. But, the maximal benefit was only 0.1 quality-adjusted life years or 5 weeks, even when endarterectomy was without risk. A separate regression model, with the degree of asymptomatic carotid stenosis as a continuous variable, suggested a possible benefit of endarterectomy for the few patients (n = 27, 3%) with an 80–99% asymptomatic carotid stenosis and hypertension. Until our results are refuted in other studies, there seems to be no firm indication for operation on the asymptomatic carotid artery in patients who have been successfully operated for a symptomatic carotid stenosis, except within the context of a randomized controlled trial.

Hypertension promotes coronary calcium deposit in asymptomatic men.

Despite its important role in coronary disease, coronary atherosclerosis has been poorly investigated in uncomplicated hypertension. Therefore, we evaluated the presence and amount (score) of coronary calcium with ultrafast computed tomography in 73 pairs of age-matched asymptomatic hypertensive or normotensive men. We also estimated the extent of peripheral atherosclerosis as the number of arterial sites (carotid, aortic, femoral) with echographic plaque. Compared with normotensive men, hypertensive men had more frequent coronary calcium (63% versus 47%), a higher calcium score (57 +/- 111 versus 18 +/- 38), and an odds ratio of calcium deposit of 1.95 (with confidence intervals [CI] 95%, 1.01 to 3.79) for any score and of 2.38 (95% CI, 1.02 to 5.52) or 4.84 (95% CI, 1.53 to 15.3) for scores above 50 or 100, respectively. Hypertensive men showed correlations of calcium score with age and hypertension duration but not with the height of blood pressure, and the odds ratio of calcium deposit between extensive and minor peripheral atherosclerosis was 4.67 (95% CI, 1.41 to 15.45) for any score and 8.63 (95% CI, 2.10 to 35.5) or 8.13 (95% CI, 1.64 to 40.3) for scores above 50 or 100. Thus, high blood pressure and in particular its duration rather than its value promotes the presence and overall extent of coronary calcium, a potential predictor of sudden coronary death, in parallel with the extent of peripheral atherosclerosis. The mechanisms of the interaction of hypertension and coronary calcification may be multifactorial and not specific to hypertension.

Prevalence and circadian variations of ST-segment depression and its concomitant blood pressure changes in asymptomatic systemic hypertension

Coronary artery disease is a major complication of hypertension; one of its manifestations is silent ischemia. The aim of this study was to assess the prevalence and circadian distribution of ST-segment depression together with concomitant blood pressure (BP) and heart rate variations. One hundred patients (male:female ratio 1:1) with a mean age (±SD) of 51 ± 8 years underwent ambulatory monitoring using the combined AMP 5600 monitor which simultaneously records a continuous Holler electrocardiogram and intermittent noninvasive BP measurements at 15-minute intervals, with extra measurements triggered by detection of a horizontal or downsloping ST depression (>1 mm and >60 seconds). Cardiovascular risk factors were fully evaluated in all patients; accurate and reliable echocardiogram enabled left ventricular mass index to be calculated in 52 patients. Twenty-three patients (15 men and 8 women) experienced a total of 72 episodes of ST depression. Duration of such episodes (mean ± SD) was 132 ± 65 seconds and amplitude was 1.51 ± 0.55 mm. Circadian distribution showed 2 peaks: on awakening and in the late afternoon periods. The mean ambulatory BP load was greater in the patients with than without ST-segment depression for both systolic and diastolic BP (135 ± 14 vs 129 ± 15 and 84 ± 8 vs 79 ± 10 mm Hg, respectively; p < 0.01). Plasma glucose (5.83 ± 0.70 vs 5.46 ± 0.71 mmol/L; p = 0.04) and self-rated work-related stress levels (22% vs 13%; p = 0.03) were also higher in patients with ST-segment depression. There were no significant differences between groups for clinical parameters, left ventricular mass index, and other cardiovascular risk factors. During ST depression episodes, systolic BP increased by 9 ± 15 mm Hg, diastolic BP by 7 ± 11 mm Hg, and heart rate by 5 ± 17 beats/min. Thus, 24-hour Hoher electrocardiographic monitoring showed ST depression episodes in 23 of 100 hypertensive patients (23%); ambulatory BP load was greater in these patients. BP variations, and mainly its elevation, may trigger such episodes of ST-segment depression.

Echographic assessment of carotid and femoral arterial structure in men with essential hypertension. Group PCVMETRA.

Extracoronary in vivo structural arterial changes were studied in asymptomatic essential hypertension. Carotid and femoral arteries were examined with B-mode echography for the presence or absence of plaque (the whole vascular segments of each vessel in the both sides) and for automated measurement of the far wall intima-media thickness (the vascular segment of each vessel proximal to the bifurcation in the right side) in 53 never treated hypertensive men and 133 normotensive men similar with regard to age, serum cholesterol levels, and smoking history. In the hypertensive group carotid plaque was more frequent (P < .05) and carotid and femoral intima-media thicknesses were greater (P < .001) than in the normotensive group. In the overall normotensive and hypertensive population intima-media thickness was independently associated with age and systolic pressure in both arteries (P < .001) and with cholesterol in the femoral artery (P < .05) while plaque was associated with systolic pressure (P < .01), and cholesterol (P < .01) in the carotid arteries and with age (P < .01), cholesterol (P < .05), and smoking (P < .001) in the femoral arteries. No significant difference in intima-media thickness in both arteries existed between hypertensive subjects with plaque and those without. Wall thickening and plaque were more frequent in hypertensive patients. Thickening was distributed homogeneously to both arteries, while plaque affected preferentially the femoral bed. The influence of age and pressure was more marked on intima-media thickness than on plaque. The lack of association between wall thickening and plaque suggested that vascular hypertrophy and early atherosis might be two different structural changes.

Immediate Management of Severe Hypertension

A patient with a hypertensive crisis should be ideally treated in an intensive care unit. The choice of oral versus parenteral drug depends on the urgency of the situation, as well as the patient's general condition. The level to which the blood pressure should be lowered varies with the type of hypertensive crisis and should be individualized. The choice of parenteral drug is dictated by the clinical manifestations and concomitant medical problems associated with the hypertensive crisis. There is no predetermined level for the goal of therapy. Complications of therapy, mainly hypotension and ischemic brain damage, can occur in patients given multiple potent antihypertensive drugs in large doses without adequate monitoring. Such complications can be minimized by gentle lowering of blood pressure, careful surveillance, and individualization of therapy. A relatively asympatomatic patient who presents with severe hypertension, that is, a diastolic blood pressure 130 to 140 mm Hg, need not be treated with parenteral drugs. These patients should be managed on an individual basis, and the usual course would be to intensify or alter the previous antihypertensive therapy. Often, asymptomatic patients or those without an acute problem are unnecessarily subjected to immediate therapy. Acute alteration of the height of the mercury column does little good and may cause harm. A significant immediate change in the patient's blood pressure may be self-gratifying to the physician but is not indicated for most patients with asymptomatic severe hypertension. Indiscriminate use of therapeutic options such as nifedipine and furosemide should be discouraged strongly. Once the patient's condition is stable, one should evaluate the patient for possible factors that may have contributed to the dangerous elevation of blood pressure, such as nonadherence to prescribed therapy or the presence or progression of a secondary form of hypertension such as a renal artery stenosis. It is crucial to recognize not only what is a hypertensive crisis but also what is not an emergency.

Hypertension and Ischemic Heart Disease Role of Dipyridamole Echocardiography Test

The aim of this study is to try to evaluate the relationship between arterial hypertension and ischemic heart disease (IHD) in the light of the physiopathologic response pattern to the dipyridamole echocardiography test (DET) in hypertensive patients, in pharmacologic washout, without any electrocardiographic ST segment depression during exercise tests or at rest. Sixty patients affected by mild to moderate asymptomatic essential arterial hypertension were studied: the subjects had a sitting diastolic blood pressure > or = 95 < or = 114 mmHg; there were 38 men and 22 women with a mean age of 49.8 +/- 7.6 years (range twenty-nine to sixty-eight). All patients had undergone high-dose DET (0.84 mg/kg in ten minutes). No patients developed side effects or asynergy in cardiac contractility during the test. In the absence of any significant coronary artery obstruction assessed angiographically, 18 patients (30%) showed ST segment depression > 1.0 mV during DET, sometimes with the presence of ventricular and/or supraventricular extrasystoles. In this group of patients the left ventricular mass index (LVMI) and duration of hypertension (in months) were higher as compared with those of the other 42 patients (respectively: 160.2 +/- 5.1 vs 129.2 +/- 9.2 g/m2, P < 0.02; and 30 +/- 4.8 vs 9 +/- 5.4 months, P < 0.007). In conclusion it is reasonable to speculate from these data that the ischemic-like" dipyridamole-induced ST segment depression, like that shown by patients affected by Syndrome X, might involve a worse prognosis in hypertensive patients. This may be because of increased coronary resistance due to structural modification or anatomic background.

Socioeconomic aspects of ACE inhibition in the secondary prevention in cardiovascular diseases.

Cardiovascular diseases are the leading causes of morbidity and mortality in the industrialized world and have become a major economic burden. Therefore, not only ethical and medical but also economic reasons suggest more intense efforts in primary and secondary prevention of cardiovascular and, especially, coronary artery disease. The prevention of the progression of heart failure and of the risks inherent in left ventricular dysfunction, including development of heart failure, reinfarctions, and death, are major cornerstones in the ambitious but economically balanced use of our resources. Major trials in chronic heart failure as well as the angiotensin-converting enzyme inhibitor pooling project in heart failure of all major studies have shown almost uniformly a reduction in hospitalizations attributable to slowing of the progression of the disease. In the Munich Mild Heart Failure Trial (MHFT) socioeconomic analysis confirmed the high economic burden of progression to the end-stages of disease: Patients with progressive heart failure had a four- to fivefold increase in hospital costs. The blunting of the progressive course of heart failure was effective enough to offset the costs of drug treatment with captopril in an analysis extrapolating the results of the socioeconomic analysis to the total trial population. Favorable results in preventive treatment of patients with asymptomatic left ventricular dysfunction, hypertension, and diabetic nephropathy also suggest that part of the additional costs of medication is outweighed by fewer hospitalizations and interventions. Thus in many cardiovascular diseases angiotensin-converting enzyme inhibitors have a favorable cost-benefit ratio and can be recommended for broader use.

Left ventricular hypertrophy and myocardial ischaemia in hypertension: The THAMES Study

A multicentre epidemiological study to detect the prevalence of myocardial ischaemia in hypertensive left ventricular hypertrophy (LVH) was performed in 188 asymptomatic male hypertensives (131 treated). The mean age was 55 (range 40-82) years with blood pressure (BP) > or = 160/100 mmHg or a systolic BP > or = 180 mmHg. The participants were screened with echocardiography, and left ventricular hypertrophy (LVH), defined as LV mass index (LVMI) > or = 130 g.m-2, was found in 127 (68%), of whom 95 were on antihypertensive treatment. Patients with LVH underwent a maximal bicycle ergometer exercise test and significant ST depression, indicating possible stress-induced ischaemia, was found in 29 men (23%). These subjects were subjected to exercise thallium-201 scintigraphy, which was normal in 14 but showed reversible perfusion defects in 15. Thus, a high prevalence of LVH (70%) was detected in male hypertensives selected only on age and BP. In addition, although chest pain on exertion excluded patients from entry, a substantial portion had signs of ischaemia (23% on exercise ECG alone, and in 52% confirmed by thallium scan). The prevalence of these risk factors should be considered when evaluating hypertensive patients.

The Degree of Blood Pressure Evaluation and End Organ Damage With Severe Hypertension: A Case-Control Study

To investigate the association of blood pressure and end-organ damage in patients with severe hypertension in a case-controlled manner, 26 patients with syndromes of acute end-organ damage and severe hypertension were compared with 25 patients with severe but asymptomatic hypertension for a variety of demographic, clinical, and basic laboratory values. Differences were assessed with the Chi-square test and multiple logistic regression analysis. End-organ damage was significantly associated with a degree of systolic and diastolic blood pressure elevation, a history of hypertensive crisis, serum creatinine, and a history of alcohol use, in multivariate analysis. The relationship to creatinine and a history of hypertensive crisis were not present in univariate analysis. The possible relationships of these factors to the pathophysiology of hypertensive crisis are discussed.

Scintigraphic and electrocardiographic evidence of silent coronary artery disease in asymptomatic hypertension: A case-control study

Objectives. This study was conducted to determine the incidence of physiologically significant coronary artery disease in a group of asymptomatic high risk men with essential hypertension and to assess the validity of noninvasive tests in a subset of these patients undergoing coronary arteriography.Methods. Two hundred twenty-six asymptomatic men (mean age 61 ± 8 years) with essential hypertension and no clinical evidence of coronary artery disease but with at least one additional coronary risk factor were studied prospectively. Fifty age- and risk factor-matched normotensive subjects were evaluated as a control group. After a minimum of 4 days without medication, subject's underwent stress thallium-201 scintigraphy, exercise and 48-h ambulatory electrocardiography, and echocardiography. Coronary angiography was performed in a subset of 34 (40%) of 84 patients with one or more positive test results.Results. A positive thallium-201 scintigram (18% vs. 6%; odds ratio 3.4, confidence interval 0.91 to 10.8, p = 0.056), exercise electrocardiograms (ECGs) (37% vs. 13%; odds ratio 4.1, confidence interval 1.5 to 11.2, p < 0.003) and ambulatory ECG (15% vs. 0%, p < 0.05) were more common in the hypertensive group than in the control group. In the cohort undergoing coronary angiography, thallium-201 scintigraphy was both sensitive and specific for epicardial atherosclerotic coronary disease (90% and 79%, respectively), but positive exercise and ambulatory ECGs occurred frequently in the absence of significant coronary stenoses. In the 39% of hypertensive patients who had mild to moderate left ventricular hypertrophy, positive exercise and ambulatory ECGs occurred at a higher rate.Conclusions. These findings suggests that physiologically significant coronary artery disease occurs more frequently in asymptomatic hypertensive men than in comparable normotensive control subjects. In the subgroup undergoing coronary arteriography, reversible scintigraphic defects were both sensitive and specific for diagnosing epicardial coronary artery disease, but exercise and ambulatory ECGs appeared to yield frequent false positive results, especially when left ventricular hypertrophy was present. These results indicate that patients with “silent” coronary artery disease can be identified among high risk hypertensive patients, but the appropriate application of such screening in clinical practice remains to be determined.

Diagnostic Accuracy of Exercise Thallium-201 Scintigraphy in Men With Asymptomatic Essential Hypertension

Coronary artery disease is responsible for much of the morbidity and mortality in patients with essential hypertension, and these complications have proven to be relatively resistant to antihypertensive therapy. However, the diagnosis of coronary disease in the hypertensive population has been considered problematic. In the present study, 30 asymptomatic patients with mild to moderate hypertension with positive exercise electrocardiograms (ECG) or stress thallium-201 scintigrams underwent coronary angiography to determine the accuracy of these tests for coronary artery disease. The exercise ECG was positive in 25 subjects, of whom 15 had significant coronary lesions and 10 did not. Thallium-201 scintigraphy proved more accurate: 17 of 18 patients with reversible abnormalities had significant obstructive coronary disease anatomically corresponding to the defect, one patient with a fixed defect had normal coronary arteries and was found to have an idiopathic cardiomyopathy, and 9 of 11 without defects had no significant lesions. The results were similar in populations with and without echocardiographic criteria for left ventricular hypertrophy. These findings indicate that despite previous suggestions to the contrary, thallium-201 scintigraphy can accurately diagnose coronary artery disease in most patients with asymptomatic essential hypertension, and that most asymptomatic hypertensive patients with physiologic evidence of myocardial ischemia have associated coronary artery disease.

Middle aortic syndrome: clinical and radiological findings.

Eight patients with the middle aortic syndrome are described. They were aged 2 months to 14 years at diagnosis; follow up was one to 11 years. Clinical presentations included asymptomatic hypertension (n = 5), severe headache, nose bleed, and chest pain (n = 1), and cardiac failure (n = 1). All had severe hypertension requiring multiple drug treatment. Diminished peripheral pulses were not helpful in the diagnosis, which is made on aortography. Associated clinical findings were Williams' syndrome (n = 3) and appreciable eosinophilia (n = 3). The differential diagnosis includes Takayasu's arteritis, fibromuscular dysplasia, and neurofibromatosis. Blood pressure was adequately controlled by medical treatment in six patients. Surgical angioplasty was performed in two. One patient remained normotensive without drug treatment 21 months after operation; the other died of sepsis and uncontrollable haemorrhage in the postoperative period. Medical treatment is satisfactory in most cases: surgery should be reserved for those in whom blood pressure cannot be controlled without unacceptable side effects of drug treatment. Although rare, the middle aortic syndrome should be considered in the differential diagnosis of hypertension when commoner causes have been excluded. Aortography is necessary for diagnosis.

Cost-effectiveness of present programs for detection of asymptomatic hypertension in relation to the severity of hypertension and proteinuric hypertension.

Proteinuric hypertension is an important cause of maternal and perinatal mortality. Eclampsia cannot always be prevented. The likelihood of identifying a new case of proteinuric hypertension at any particular visit is very low using traditional antenatal care schedules, and care could be focused on women at higher risk.

What causes ST-T abnormalities in asymptomatic hypertensives: LVH, ischemia or both?

What causes ST-T abnormalities in asymptomatic hypertensives: LVH, ischemia or both?

Rapid reduction of severe asymptomatic hypertension : Zeller KR, Kuhnert LV, Matthews C. Arch Intern Med. 1989;146:218-9

Rapid reduction of severe asymptomatic hypertension : Zeller KR, Kuhnert LV, Matthews C. Arch Intern Med. 1989;146:218-9

Chronic Low Back Pain, Description, and Attributional Styloe

Twenty consecutive, chronic low back pain patients admitted to our pain treatment unit completed the Attributional Style Questionnaire (an instrument that detects a cognitive style that is correlated with, and that predicts, depression) and the Beck Depression Inventory. An age, sex, and education-matched group of normal subjects, a group of patients with asymptomatic essential hypertension, and a group of patients with end-stage renal disease receiving dialysis treatment served as controls. The majority of the chronic-pain and renal-dialysis patients had elevated depression scores, whereas none of the normal subjects or hypertensive patients were outside the nondepressed range. The Attributional Style scores of the pain and renal dialysis patients were significantly deviant from the normal control group, but no more so than those of the patients with hypertension. The results of this study suggest that individuals with a chronic medical condition, either symptomatic (chronic low back pain or renal disease) or asymptomatic (essential hypertension) in nature, develop an attributional style characteristic of depression. These data neither lend support nor refute the thesis that chronic pain syndromes are a variant of, or a masked, depression. Rather, this research implies that a more important question is what identifiable risk factors (for example, attributional style) predispose patients with chronic pain to develop a depressive illness.