No abstract

This study suggests that hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and a greater decline in renal function than do patients with normal UAE.

We previously showed that a high salt diet increases glomerular capillary pressure in salt-sensitive hypertensive patients and suggested that this may underlie the greater propensity of these patients to develop renal failure. Because microalbuminuria is considered an initial sign of renal damage, we have tested whether salt-sensitive patients display greater urinary albumin excretion than salt-resistant hypertensive patients. Twenty-two patients were placed on a low sodium intake (20 mEq/d) for 7 days followed by a high sodium diet (250 mEq/d) for 7 more days. Twelve patients were classified as salt sensitive and 10 as salt resistant. Urinary albumin excretion was greater in salt-sensitive than saltresistant patients (54±11 versus 22±5 mg/24 h, P<.01). During the low sodium diet, glomerular filtration rate, renal plasma flow, and filtration fraction were similar between the two groups. During the high sodium intake, glomerular filtration, renal plasma flow, filtration fraction, and calculated intraglomerular pressure did not change in salt-resistant patients; in salt-sensitive patients, however, renal plasma flow decreased, and filtration fraction and intraglomerular pressure increased, whereas glomerular filtration rate did not change. Urinary albumin excretion was significantly correlated with glomerular capillary pressure. Salt-sensitive patients displayed higher serum levels of low-density lipoprotein cholesterol and lipoprotein(a) and lower levels of high-density lipoprotein cholesterol than salt-resistant patients. These studies have shown greater urinary albumin excretion and serum concentrations of atherogenic lipoproteins in salt-sensitive than in salt-resistant hypertensive patients, suggesting that salt sensitivity may be a marker for greater risk of renal and cardiovascular complications. (Hypertension. 1994;23:195-199.)

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

Microalbuminuria in patients with essential hypertension is associated with increased incidence of cardiovascular morbidity and mortality. Reduction of urinary albumin excretion (UAE) with therapy could reduce cardiovascular events. The long-term effect of commonly used antihypertensive agents on UAE has not been properly investigated. In the present study, we have prospectively studied the effects of therapy for 24 months with a converting enzyme inhibitor, enalapril, or a calcium channel blocker, nicardipine, on UAE in 40 patients with essential hypertension and microalbuminuria. Enalapril and nicardipine were equally effective in reducing arterial pressure. However, enalapril decreased UAE from 77.1 +/- 10.4 to 30.4 +/- 7.9 mg/24 h after 1 year, and to 24.7 +/- 4.8 (P < .01) after 2 years of therapy. UAE however, did not change in patients treated with nicardipine (from 65.2 +/- 12 to 73 +/- 14 after 1 year, and to 52.7 +/- 21 mg/24 h after 2 years of therapy). The impact of reducing UAE on overall cardiovascular morbidity and mortality and on future progression of renal failure in patients with essential hypertension remains to be established.