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Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.
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PMID:Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders. 138 18

We have investigated the cellular basis for the clinical and epidemiologic linkage of hypertension, left ventricular hypertrophy (LVH), obesity, and non-insulin-dependent diabetes mellitus (NIDDM) and have studied cytosolic free calcium and free magnesium levels in these syndromes. Specifically, intracellular free calcium is elevated and free magnesium is deficient in hypertension, and both are related (directly and inversely, respectively) to the ambient level of blood pressure, to LV mass index (and thus to the degree of cardiac hypertrophy), and to the hyperinsulinemia and insulin resistance of essential hypertension. Dynamically, the ability of dietary salt loading to elevate blood pressure corresponds to its ability to elevate cytosolic free calcium and reciprocally to suppress free magnesium levels. Conversely, the ability of calcium channel blockade to reverse salt-induced hypertension is related to its ability to prevent these transmembrane ionic effects. Higher steady-state free calcium or lower free magnesium, or both, are also observed in clinical states linked to hypertension, such as obesity and NIDDM. Oral glucose loading in normal subjects itself elevates free calcium and suppresses free magnesium levels, as does hyperglycemia in vitro. These data suggest an ionic hypothesis of cardiovascular and metabolic disease, in which a generalized defect in cell ion handling is present in all tissues, resulting in higher steady-state free calcium and lower free magnesium levels. In pancreatic beta cells, this would produce hyperinsulinemia; in fat and skeletal muscle, cause peripheral insulin resistance; and in renal tissue, increase proximal sodium resorption and increase urinary calcium excretion--all features of essential hypertension. In vascular smooth muscle, high cytosolic free calcium would increase smooth muscle tone and cause vasoconstriction, and in heart muscle, independent of blood pressure, would increase contractility and predispose to LVH. Therefore, what may appear clinically to be the separate syndromes of hypertension, obesity, and NIDDM may pathophysiologically be different manifestations of the same underlying cellular defect, thus explaining their frequent clinical coexistence. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion-specific agents, such as calcium channel blocking drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent excess morbidity and mortality of the concurrent cardiac, vascular, and metabolic aspects of the hypertensive state.
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PMID:Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders. 138 62

Felodipine is a dihydropyridine calcium antagonist which may be administered once daily in an extended release (ER) formulation. As monotherapy in older patients with mild to moderate essential hypertension, felodipine ER once daily provides effective control of blood pressure (BP). The drug has also been effective, either as monotherapy or in combination with other antihypertensive medications, in comparisons with other antihypertensive agents, and does not adversely affect lipid profiles or, in patients with diabetes mellitus, glycaemic control. Results in patients with angina pectoris and congestive heart failure indicate a potential role for felodipine ER in these indications and data also suggest the drug reduces left ventricular hypertrophy. In addition, felodipine ER appears suitable for use in patients with concomitant respiratory disease, renal or hepatic dysfunction, cerebrovascular or peripheral ischaemic disease, or gout, making it particularly useful in the elderly who often have more than one significant clinical condition. Felodipine ER has generally been well tolerated by older patients in clinical trials, although further confirmation in the long term is desirable. Thus, felodipine ER effectively lowers BP in older patients with essential hypertension with the added convenience of once daily administration. It may be used as monotherapy or in combination with other antihypertensive agents and is a practical advance in the treatment of hypertension in the elderly.
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PMID:Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in older patients. 139 20

To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi-squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria.
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PMID:[Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients]. 143 89

A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.
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PMID:Report of a Japanese girl with Marfan syndrome associated with insulin-dependent diabetes mellitus. 144 30

The risk factors of ischemic cerebrovascular disorders in 77 young patients (< or = 40 years) were compared to those in 138 older patients (> 40 years). The risk factor profile of patients with juvenile stroke was considerably different from that of older patients. Migrainous headache and mitral valve prolapse occurred more frequently in the younger age group, whereas hypertension, diabetes mellitus, high levels of cholesterol and triglycerides were found more often in older patients with stroke. 65% of the women under the age of 40 took oral contraceptives which compares to the baseline community value of 28% of women in childbearing age in this country. Cardiac disorders such as atrial fibrillation, left ventricular hypertrophy, coronary heart disease including a history of myocardial infarction, as well as mitral valve disease were demonstrated more often in the group of elderly patients. 7 out of 77 younger patients (9.1%), and 59 out of 138 older patients (42.8%) were considered to belong to a group with "high cardiac risk for stroke". The results of this study indicate that electrocardiographic screening is of prime importance for detecting cardiac risk factors. However, echocardiographic examination often yields additional diagnostic information, particularly in younger patients. The conflicting opinions concerning the relevance of certain risk factors for ischemic stroke could partly be explained by the fact that these risk factors are distributed unevenly depending on age.
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PMID:Different risk factor profiles in young and elderly stroke patients with special reference to cardiac disorders. 146 Apr 76

Hypertensive obese subjects run an increased cardiovascular risk. Their predominantly abdominal obesity is often associated with hypertriglyceridaemia and insulin-resistant diabetes, and their cardiovascular status is characterized by cardiac hyperdynamics and hypervolaemia responsible for left ventricular hypertrophy and dilatation. Insulin resistance and subsequent hyperinsulinaemia are thought to explain the obesity-hypertension association, the cardiovascular effects observed and the metabolic and cardiovascular complications which might result from this situation. Successful control of both arterial pressure and overweight should contribute to regression of the left ventricular hypertrophy. Simultaneous treatment of abnormalities in carbohydrate and lipid metabolism is also necessary to prevent cardiovascular complications.
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PMID:[Cardiovascular consequences of obesity associated with arterial hypertension]. 146 76

Hypertension is a powerful predisposing risk factor for cardiovascular disease at all ages and in both sexes. Epidemiological assessment indicates the largest risk ratios for stroke and congestive heart failure (CHF), but coronary heart disease (CHD) is the most common and most lethal sequela of hypertension. Examination of the risk of cardiovascular sequelae in the hypertensive population indicates that this is not uniform and varies over a 10-fold range, depending on the associated risk factors. Systolic pressure merits greater consideration than the diastole pressure because isolated systolic hypertension is a powerful cardiovascular risk at all ages. Furthermore, recent trials have indicated the benefit of therapy for systolic-based hypertension in the elderly, even using a diuretic, for coronary disease as well as stroke. Persons with hypertension have a high prevalence of associated cardiovascular risk factors, including elevated cholesterol, reduced HDL-C, diabetes, left ventricular hypertrophy (LVH), and obesity. About 9% under the age of 65 years have an associated overt cardiovascular disease; above age 65 about 30% are so afflicted. Each of these risk factors can double the risk associated with hypertension. Because they are so common, a large fraction of the disease sequelae of hypertension is attributable to these associated risk factors. The high risk of coronary disease in hypertensive patients is concentrated in those with a high total/HDL-cholesterol ratio, impaired glucose tolerance, high fibrinogen, ECG abnormalities, and cigarette smokers. Stroke risk in hypertensive persons is concentrated in those with cardiovascular disease, diabetes, atrial fibrillation, LVH and cigarette smoking.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potency of vascular risk factors as the basis for antihypertensive therapy. 148 3

Over the past decade we have seen a shift in the strategy for the treatment of hypertension, from stepped therapy--involving a highly structured, unvarying series of steps--to recommendations for more individualized treatment. How shall we accomplish that goal? Severe hypertension provides a clear indication to bypass earlier recommendations. Demographic data such as age, gender, and race, often cited, have proved less helpful. Concomitant medical problems, which are found in greater than 50% of hypertensive patients, are most often the crucial determinants in the selection of antihypertensive therapy. Concurrent coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, chronic obstructive pulmonary disease, borderline cognitive dysfunction, anxiety, and depression are all common. Each has implications for antihypertensive therapy. Moreover, blood pressure reduction is a surrogate for our real goal, which is reduction of cardiovascular risk. Thus, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, hyperlipidemia, and insulin resistance as additional risk factors in hypertension. Consideration of all of these factors makes it possible to individualize antihypertensive therapy in most patients.
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PMID:Evolution of the treatment of hypertension: what really matters in the 1990s? 151 35

To determine the predictive value of adenosine thallium-201 myocardial imaging for perioperative cardiac events, 60 consecutive patients referred for preoperative cardiac evaluation were studied before vascular (n = 25), orthopedic (n = 14), or general (n = 21) surgery. Tomographic (n = 52) and planar (n = 8) thallium-201 imaging was performed after adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Two blinded expert observers graded results of adenosine thallium-201 studies as normal (33%), fixed defect only (2%), reversible defect only (48%), and combined (fixed and reversible) defects (17%). After 6 +/- 3 months of follow-up, 81% proceeded to surgery and 43% underwent preoperative coronary angiography. Clinical variables that correlated with perioperative cardiac events were a history of diabetes mellitus (p = 0.05), left bundle branch block (p = 0.02), and left ventricular hypertrophy (p = 0.06) on the resting ECG. This clinically "high-risk" group had an event rate of 22% as compared with no cardiac events in patients in the "low-risk" group without these clinical characteristics (p = 0.005). Stepwise logistic regression analysis revealed that the presence of a combined (fixed and reversible) adenosine thallium-201 defect (p = 0.0007), three-vessel coronary artery disease (p = 0.001), and left bundle branch block (p = 0.02) was predictive of subsequent cardiac events with relative risk ratios of 4.9, 2.9, and 2.2, respectively. Therefore the presence of an adenosine thallium-201 perfusion defect is correlated with and predictive of an increased risk of perioperative cardiac events in patients referred for preoperative risk evaluation.
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PMID:Determination of perioperative cardiac risk by adenosine thallium-201 myocardial imaging. 152 2


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