Prevalence of Hypertension in Chronic Cocaine Users

Abstract

The association of cocaine and acute hypertension is well known; however, cocaine use has not generally been linked to chronic hypertension. We hypothesized that chronic use of cocaine over time would increase the prevalence of hypertension and that cocaine induced vasoconstriction would result in urine protein leakage, manifested by microalbuminuria. Therefore, we studied a population of predominantly black male patients admitted for addiction treatment whose drug of dependence was cocaine. A urine toxicology screen was considered positive if cocaine was detected within 24 h prior to or during admission to the hospital. A total of 301 patients with normal renal function were observed over their 2 week hospitalization. The majority (62%) of the patients were normotensive regardless of the status of their initial urine toxicology screen. Twenty percent of the population had acutely elevated blood pressure that normalized within 1 day, whereas 18% had blood pressure chronically >140/90 mm Hg (chronic hypertension). Levels of systolic and diastolic blood pressures were examined at age deciles and compared to the NHANES III (Third National Health and Nutrition Examination Survey) data for a predominantly black population. There was no significant difference in blood pressure with age in the cocaine users compared to the NHANES groups. Random urine samples were screened for the presence of microalbuminuria and no significant elevation was detected in any of the samples tested. We conclude that chronic cocaine use is associated with acute but not chronic hypertension in middle-aged black males. Cocaine use does not cause microalbuminuria.

Cocaine, hypertension, microalbuminuria

Cocaine, widely used as a mood elevating drug, possesses powerful vasoconstrictor properties that render it capable of causing myocardial infarction, arrhythmia, sudden death, stroke, seizures, bowel necrosis, and numerous other complications.^1,,,,–6 Acute hypertension is another well-known manifestation of cocaine use,^6,7 as is acute renal failure^5,6,8 occurring either in the presence of rhabdomyolysis ⁸ or due to vasoconstriction,⁹ such as has been described with ergotamine,¹⁰ epinephrine,¹¹ and amphetamine derivatives.¹² Cocaine has been shown to cause severe narrowing of intrarenal arteries due to intimal fibrosis,¹³ a finding recently confirmed in an autopsy study of cocaine users.¹⁴ It is not known, however, if clinically significant hypertension or chronic renal impairment can occur, either as a late consequence of acute injury or as a result of chronic vasoconstriction. In an attempt to answer these questions, we have studied a group of cocaine users for the presence of hypertension and microalbuminuria, using the latter as a test of early renal injury.

Methods

Patients

We screened veterans admitted to the inpatient drug treatment ward during a 2 year period for the presence or absence of hypertension based on their initial and subsequent blood pressure readings. They were usually admitted for a period of about 2 weeks. Accrual of patients was not necessarily consecutive due to staff availability; however, the interval of nonaccrual was generally <1 or 2 months. Patients readily consented to be included in the study with few exceptions. A blood pressure > 140/90 mm Hg was considered to be hypertensive. All subjects considered cocaine as a drug of addiction, which was documented at some point by a positive urine toxicology screen, and many admitted to use of other substances as well. Additional information regarding medical history, medications, and drug use history was obtained by patient interview or chart review. Also noted were the results of routine laboratory tests: urinalysis, serum blood urea nitrogen (BUN) and creatinine levels, and urine toxicology. Hypertensive and normotensive patients were randomly screened for the presence of microalbuminuria.

Urinary Albumin Measurement

Freshly voided random urine specimens were obtained and frozen until assayed. Briefly, urine was dialyzed against saline using dialysis membranes with a molecular weight cutoff of 14,000 daltons to remove interfering substances. Total protein was measured by a colorimetric method (Bio-Rad, Richmond, CA) using albumin as a standard, before and after absorption of the albumin fraction by ion exchange chromatography (CM Affigel Blue, Bio-Rad) to correct for differences in albumin and globulin binding to the Bio-Rad dye. This chromatographic method compares favorably with radioimmunoassay measurement (r = 0.91) for microalbuminuria.¹⁵ Urine protein measurements were normalized for urine creatinine, which was measured by the standard picric acid colorimetric method. The results were expressed as a ratio of albumin to creatinine, with the upper limit of normal being < 0.03.

Statistics

Standard statistical analysis was done using Student t test or χ² test where appropriate.

Results

We screened 301 patients: 284 of these were black, 10 white, and 7 Hispanic. There were four women (one white and three black). Table 1 shows the demographic data for the group and information about their drug habits. Although all used cocaine chronically, cocaine was the sole drug used by only 10% of subjects; 48% also took heroin, and 77% used alcohol as well as cocaine. Those with a greater number of years of drug use tended to use additional substances along with cocaine (alcohol and heroin). Figure 1 shows the mean systolic and diastolic blood pressures by age decile during the initial period of hospitalization, at which time a urine toxicological exam was obtained. This figure also depicts similar data for comparison of black subjects from the Third National Health and Nutrition Examination Survey (NHANES), 1988–1991,¹⁶ because the majority of patients in our study were black. There was no significant difference in systolic and diastolic blood pressures between our study group and a group of comparable age and race.

Table 1.

Demographics and Drug Use

	n (Years of Cocaine Use)
Male/female	297/4
Black	284 (12.9)
White	10 (12.6)
Hispanic	7 (7.3)
Other	0
Chronic cocaine abuse only	30 (8.6)
Chronic cocaine and alcohol use	232 (12.5)
Chronic cocaine and heroin use	145 (14.3)

n = 301.

Systolic and diastolic blood pressure by age decile. Comparision of present study versus data from NHANES III.

Figure 1.

For further analysis the patients were divided into six arbitrary groups according to blood pressure (systolic pressure > 140 mmHg or diastolic pressure < 90 mmHg), known diagnosis of chronic hypertension and whether treated or untreated, and toxicological status at the time of the initial blood pressure measurement. This was done in order to eliminate the component of acute hypertension from recent cocaine use and increase the likelihood of detecting chronic hypertension. Patients whose initial blood pressure was elevated, were not known to have chronic hypertension, and had subsequent normal blood pressures during their hospitalization, were considered to have “acute hypertension.” Thus, the patients were separated into the following groups:

1. Normotensive, cocaine negative;

2. Acute hypertension, no known history of hypertension, cocaine negative;

3. Chronic hypertension, cocaine negative;

4. Normotensive, cocaine positive;

5. Acute hypertension, cocaine positive; and

6. Chronic hypertension, cocaine positive.

Table 2 shows the age, mean arterial pressure (MAP), creatinine, weight, and number of years of cocaine use for each of the above groups. As expected, MAP was significantly higher in groups 2, 3, 5, and 6 than in groups 1 and 4 (P < .001). The MAP was not different in the acute or chronic hypertensive groups whether cocaine positive or negative. Among cocaine-positive patients those with acute and chronic hypertension weighed significantly more than the normotensive ones. Serum creatinine was not significantly different among the groups, whether the toxicology screen was positive or negative.

Table 2.

Clinical Data by Group

Toxicology Screening*– Blood Pressure	N (%)	Age (years)	MAP (mm Hg)	Serum Creatinine (mg/dL)	Weight (lbs)	Years of Cocaine Use
1. Negative–normal BP	53 (18)	41.2	89.1	0.99	165.3	11.5
		1.01	1.29	0.02	3.57	1.56
2. Negative–acute HTN	12 (4)	40.0	112.7	1.00	172.0	10.9
		1.77	1.82	0.07	8.77	2.42
3. Negative–chronic HTN	7 (2)	45.7	103.1	1.13	180.3	16.8
		4.27	6.38	0.06	26.6	7.67
4. Positive–normal BP	133 (44)	39.8	90.1	1.08	162.5	11.9
		0.63	0.82	0.08	3.23	0.82
5. Positive–acute HTN	47 (16)	42.3	113.5	0.99	179.0	12.9
		1.2	1.18	0.03	7.49	1.19
6. Positive–chronic HTN	49 (16)	47.6	110.4	1.04	182.4	15.2
		1.1	2.2	0.04	5.9	1.6

*

All patients were cocaine users, toxicology was determined at the time of the blood pressure measurement, resulting in group assignment.

Results are mean ± SEM.

Forty-one patients were randomly screened for microalbuminuria, 23 of whom were hypertensive at some point during their hospitalization. Only two patients had significant microalbuminuria (albumin to creatinine ratio > 0.03), albeit at very low levels, 0.04 and 0.05.

Discussion

Several years ago, we described a group of patients who had smoked or sniffed cocaine for a number of years and who presented with chronic renal failure and severe hypertension, the latter often out of proportion to the degree of changes present in the optic fundi.⁷ The patients seemed to have either hypertensive nephrosclerosis or underlying primary renal disease. We postulated that in these patients, who were black and known to have increased reactivity of the intrarenal vasculature,¹⁷ cocaine had set up a vicious circle and hastened progression to renal failure by exacerbating their hypertension and possibly by causing sustained intrarenal vasoconstriction.¹³ Working with similar patients in the Watts district in Los Angeles, Thornhill-Joynes et al¹⁸ also reported that cocaine appeared to play a major role in the development of their end-stage renal disease and suggested that further studies regarding the association between cocaine use, hypertension, and renal disease were warranted.

In this study, we investigated whether cocaine-using subjects admitted for drug treatment have a higher than normal incidence of high blood pressure, a reasonable supposition considering the frequency of cocaine-induced acute hypertension. Our hypothesis, however, was not borne out by the data obtained. In fact, there was little evidence for renal disease in this population that had used cocaine for a mean period of 12 years. It is likely that the patients observed previously had more risk factors for renal and hypertensive target organ disease than the population in the current study. Moreover, only 10% of the patients studied had used cocaine exclusively, and the concomitant use of heroin and alcohol may have opposing effects on blood pressure. In a previous study of heroin users,¹⁹ there was a vanishingly low prevalence of hypertension, despite a large proportion of black subjects. This was felt to be due to the concomitant use of barbiturates by a large proportion of the study group. Seventy-seven percent of the patients in the current study admitted to some degree of alcohol use, a known risk factor for high blood pressure. Despite this, no increased tendency towards high blood pressure was found in this group. In addition, many drug users are also tobacco smokers, a habit also associated with hypertension. We did not quantitatively collect data on these factors and the NHANES study did not specify the amount of alcohol, drug, and tobacco use, thus the role of these additional factors can not be ascertained. It is of interest that the patients manifesting acute and chronic hypertension with a positive toxicology screen for cocaine weighed significantly more than the normotensive ones. This relative higher body weight was also observed in those with chronic hypertension who were negative for cocaine toxicology. Obesity is a well recognized risk factor for hypertension²⁰ and, despite chronic cocaine use, these patients tended to maintain a heavier weight and manifest elevated blood pressures.

The ability of cocaine to cause an acute hypertensive response is well recognized, but only one recent large study has investigated whether cocaine may cause chronic hypertension. The Coronary Artery Risk Development in Young Adults Study (CARDIA)²¹ longitudinally studied a cohort of black and white individuals over a period of 7 years and demonstrated stable systolic and diastolic blood pressures and the prevalence of hypertension over the duration of the study. These results are compatible with those of this study, although the CARDIA study had the advantage of looking at blood pressure over a period of years. Cocaine acutely causes hypertension by blocking neuronal reuptake of catecholamines and dopamine³ and it also enhances the release of norepinephrine and increases catecholamine receptor sensitivity. In an autopsy study of cocaine-induced cerebral hemorrhage, Kibayashi et al²² noted that 88.5% of cases had hypertensive cardiovascular disease as shown by increased heart weight, left ventricular hypertrophy, and nephrosclerosis, yet this presumption of an increased incidence of hypertension may be inflated due to the association of cardiac hypertrophy with cocaine in the absence of hypertension.²³

We also did not find an increased incidence of renal disease in this population, despite the known clinical association of cocaine use with acute renal failure and with severe hypertension.^7,24 Experimentally, several investigators have also looked at the possible role of cocaine in inducing renal disease. Thus, Pan and Singhal²⁵ demonstrated an increased uptake of IgG aggregates by the glomeruli and mesangium by cocaine, suggesting that cocaine may trigger immune complex accumulation in the kidney. In a study of cocaine effects on rats,²⁶ chronic administration of the drug resulted in glomerular capillary wall damage, tubular epithelial swelling, and progression to glomerular sclerosis and atrophy. In another study, Mattana et al,²⁷ demonstrated the ability of macrophage secretory products induced by cocaine to cause mesangial proliferation in cultured cells, providing a possible mechanism for cocaine to cause glomerular damage and renal disease. Thus, although cocaine has been shown to induce renal lesions in experimental settings, we were unable to show that prolonged use caused an increased prevalence of renal disease in this study of chronic drug users. Perhaps screening a large population of subjects with some renal impairment and following them over a period of years would be more enlightening as to the propensity of cocaine to exacerbate preexisting disease rather than producing it de novo.