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PURPOSE OF REVIEW: The objective of this manuscript is to review and describe the relationship between Lp(a) and diabetes, exploring both their association and synergy as cardiovascular risk factors, while also describing the current evidence regarding the potential connection between low levels of Lp(a) and the presence of diabetes. RECENT FINDINGS: Epidemiological studies suggest a potential relationship between low to very low levels of Lp(a) and diabetes. Lipoprotein(a), or Lp(a), is an intriguing lipoprotein of genetic origin, yet its biological function remains unknown. Elevated levels of Lp(a) are associated with an increased risk of cardiovascular atherosclerosis, and coexisting diabetes status confers an even higher risk. On the other hand, epidemiological and genetic studies have paradoxically suggested a potential relationship between low to very low levels of Lp(a) and diabetes. While new pharmacological strategies are being developed to reduce Lp(a) levels, the dual aspects of this lipoprotein's behavior need to be elucidated in the near future.

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OBJECTIVE: In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients. METHODS: Seventy-one FH patients (39 ± 15 years, LDL-cholesterol=274 ± 101; HDL-cholesterol=50 ± 14 mg/dl) and 66 normolipidemic subjects (NL) (38 ± 11 years, LDL-cholesterol=105 ± 27; HDL-cholesterol=52 ± 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37°C, 1h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction. RESULTS: Transfer of UC to HDL was lower in FH than in NL (5.6 ± 2.1 vs 6.7 ± 2.0%, p=0.0005) whereas TG (5.5 ± 3.1 vs 3.7 ± 0.9%, p=0.018) and PL (20.9 ± 4.6 vs 18.2 ± 3.7 %, p=0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I. CONCLUSION: FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.

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La disminución de colesterol-LDL (c-LDL) se considera meta principal del tratamiento de pacientes con riesgo cardiovascular. Sin embargo, pacientes con Enfermedad Renal Crónica (ERC) en hemodiálisis presentan c-LDL menor de 100 mg/dL, aumentos moderados de triglicéridos y baja frecuencia de colesterol-HDL por debajo de valores deseables. Esta condición se encuadra dentro del fenómeno conocido como "epidemiología inversa", en la cual la conocida asociación prevalente entre hipercolesterolemia, hipertensión arterial, obesidad y morbimortalidad por eventos cardiovasculares no se encuentra y, por el contrario se invierte la estrecha relación de estos parámetros con eventos cardiovasculares propia de los pacientes no hemodializados. Por un lado el 35% de los pacientes con ERC presentan diabetes mellitus tipo 2 y por otra parte, existen otros factores patogénicos menos conocidos como la Lipoproteína asociada a Fosfolipasa A2, la Proteína C Reactiva, los remanentes lipoproteicos, la Lp(a) y enzimas y proteínas asociadas a la HDL, como la Paraoxonasa y Apo A-I. El conjunto de factores descritos podrían reemplazar, en pacientes con ERC en hemodiálisis, al colesterol-LDL (c-LDL), típico analito que en otros pacientes actúa como factor de riesgo y/o patogénico de aterosclerosis y no sólo como marcador circulante. Una explicación plausible respecto al c-LDL disminuído es la modificación cualitativa de LDL por oxidación, glicación, carbamilación, la presencia de LDL pequeñas y densas, fenómenos inflamatorios y malnutrición.(AU)

The decrease in LDL cholesterol (LDL-C) is considered the main goal in the treatment of patients with atherosclerotic cardiovascular risk. However, patients with chronic kidney disease (CKD) on hemodialysis have LDL-C below 100 mg/dL, moderate increases in triglycerides and low frequency of HDL cholesterol values below desirable.This condition fits into the phenomenon known as "reverse epidemiology", in which the normal relationship between hypercholesterolemia, high blood pressure, obesity and cardiovascular morbidity and mortality is not found; contrarily, there is a reversal in the close relationship of these parameters with cardiovascular events typical of non-hemodialyzed patients. On the one hand, 35% of CKD patients have Type 2 diabetes mellitus and on the other hand, there are other lesser known pathogenic factors such as lipoprotein-associated phospholipase A2, C-reactive protein, remnant lipoproteins, Lp(a) and enzymes and proteins associated to HDL such as paraoxonase and Apo A-I. The set of factors described could replace, in CKD patients on hemodialysis, LDL cholesterol, a typical analyte that, in other patients, acts as a risk and/or pathogenesis factor of atherosclerosis and not only as a circulating marker. A likely explanation for decreased C-LDL cholesterol is qualitative modification of LDL as a result of oxidation, glycation, carbamylation, occurrence of small and dense LDL, inflammatory phenomena and malnutrition.(AU)

A diminuiþÒo de colesterol-LDL (c-LDL) considera-se objetivo principal do tratamento de pacientes com risco cardiovascular. Entretanto, pacientes com Doenþa Renal Cr¶nica (ERC) em hemodiálise apresentam c-LDL menor de 100 mg/dL, aumentos moderados de triglicerídeos e baixa frequÛncia de colesterol-HDL inferior aos valores desejáveis. Esta condiþÒo se enquadra dentro do fen¶meno conhecido como "epidemiologia reversa", na qual a conhecida associaþÒo prevalente entre hipercolesterolemia, hipertensÒo arterial, obesidade e morbimortalidade por eventos cardiovasculares nÒo se encontra e, pelo contrário se inverte a estreita relaþÒo destes parÔmetros com eventos cardiovasculares própria dos pacientes nÒo hemodialisados. De um lado, 35% dos pacientes com ERC apresentam Diabetes Melito tipo 2 e do outro, existem diferentes fatores patogÛnicos menos conhecidos como a Lipoproteína associada a Fosfolipase A2, a Proteína C Reativa, os remanescentes lipoproteicos, a Lp(a) e enzimas e proteínas associadas O HDL, como a Paraoxonase e Apo A-I. O conjunto de fatores descritos poderia substituir, em pacientes com ERC em hemodiálise, o colesterol-LDL (c-LDL), típico analito que em outros pacientes age como fator de risco e/ou patogÛnico de aterosclerose e nÒo só como marcador circulante. Uma explicaþÒo plausível a respeito do c-LDL diminuído é a modificaþÒo qualitativa de LDL por oxidaþÒo, glicaþÒo, carbamilaþÒo, a presenþa de LDL pequenas e densas, fen¶menos inflamatórios e malnutriþÒo.(AU)

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OBJETIVO: Avaliar níveis de lipoproteína(a) em pacientes com síndrome antifosfolípide primária (SAFP) e suas possíveis associações clínicas e laboratoriais. MÉTODOS: Estudo transversal de 46 pacientes (93,5 por cento do sexo feminino) com SAFP (critérios de Sapporo). Foram avaliados os dados demográficos e clínicos, medicações, anticorpos antifosfolípides, além da medida dos níveis séricos em jejum da lipoproteína(a). RESULTADOS: Os níveis de lipoproteína(a) ( > 30 mg/dL) foram vistos em 43,5 por cento dos pacientes com SAFP, com média de 42 ± 43,5 mg/dL. Comparando-se o grupo com níveis maiores que 30 mg/dL com o grupo de pacientes com níveis menores ou iguais a este valor, não foram observadas diferenças significativas em relação a dados demográficos (idade, sexo, cor branca, peso, altura e índice de massa corporal), manifestações da doença (eventos arteriais, venosos, obstétricos, plaquetopenia), eventos cardiovasculares (infarto agudo do miocárdio, angina, acidente vascular cerebral), comorbidades, estilo de vida (atividade física, tabagismo atual e pregresso), uso de medicações (corticoide atual e pregresso, estatina, cloroquina), bem como à frequência de positividade de anticorpos antifosfolípides. CONCLUSÃO: Pacientes com SAFP apresentam uma frequência elevada de níveis aumentados de lipoproteína(a). Entretanto, nenhuma associação dessa anormalidade com as variáveis clínicas e laboratoriais estudadas foi encontrada.

OBJECTIVE: To evaluate levels of lipoprotein(a) in patients with primary antiphospholipid syndrome (PAPS) and its possible associations with clinical and laboratory features. METHODS: Transversal study with 46 (93.5 percent female) PAPS patients (Sapporo criteria). Demographic, clinical, drugs use, and antiphospholipid antibodies data were evaluated, as well as measurements of lipoprotein(a) serum fasting levels. RESULTS: Elevated levels of lipoprotein(a) ( > 30 mg/dL) were observed in 43.5 percent of PAPS patients, with a mean of 42 ± 43.5 mg/dL. A comparison between patients with lipoprotein(a) higher than 30 mg/dL and those with < 30 mg/dL did not show any differences regarding demographics (age, gender, white race, weight, height, body mass index), diseases features (arterial, venous or obstetric events, thrombocytopenia), cardiovascular manifestations (acute myocardial infarct, angina, stroke), comorbidities, life style (physical activity, smoking), drugs use (corticosteroids, statins, chloroquine), as well as the frequency of positivity of antiphospholipid antibodies. CONCLUSION: PAPS patients had a high frequency of increased levels of lipoprotein(a), however there was no association of this abnormality with the clinical and laboratorial features herein studied.

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Con el objetivo de investigar la función que ejerce la lipoproteína (a) como factor de riesgo independiente en diferentes procesos cardiovasculares se determinaron los valores de la misma en 50 sujetos sin enfermedad arterial coronaria y en 92 pacientes isquémicos. Se determinaron las concentraciones de colesterol total, HDL, LDL, triglicéridos y VLDL. Aunque las concentraciones promedio de Lp(a) fueron superiores en los pacientes que en los controles, sólo se obtuvo diferencias significativas para el grupo angina (p=0,036*). Los factores de riesgo adicionales que mostraron valores patológicos fueron el colesterol total, las LDL, HDL y los triglicéridos con diferencias significativas para los 2 primeros de p < 0,05 y p < 0,01. Se concluyó que en nuestro estudio, la lipoproteína (a) constituyó un factor de riesgo independiente de enfermedad cardiovascular por lo que su determinación debe ser incluída en las prácticas clínicas.

In order to investigate the function of lipoprotein (a) as an independent risk factor in different cardiovascular processes, its values were determined in 50 subjects with no coronary arterial disease and in 92 ischemic patients. The concentrations of total cholesterol, HDL, LDL, triglycerides and VLDL were determined. Though the average concentrations of Lp(a) were higher in patients than in controls, significant differences were only obtained for the angina group (p=0.0368*). The aditional risk factors showing pathological values were total cholesterol, LDL, HDL and triglycerides with marked differences for the first two of p<0.05 and p<0.01. It was concluded that in our study lipoprotein(a) was a risk factor independent of cardiovascular disease. Therefore, its determination should be included in the clinical practices.

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PURPOSE--To evaluate the effects of pravastatin on lipoproteins, Lp (a), apo B and apo A-I and its tolerability in primary hypercholesterolemic patients in our outpatient lipid clinic. METHODS--Twenty-two primary hypercholesterolemic patients were evaluated. They had all been treated previously with other hypocholesterolemic drugs, including the statins, forming a specific and homogeneous group with hypercholesterolemia and definite coronary risk. After 7 weeks with American Heart Association phase I diet and placebo drug, pravastatin was administered during 12 weeks. All patients received an initial daily dose of 10 mg for six weeks. After this period, this dose was increased to 20 mg. The levels of cholesterol, triglycerides, high-density lipoprotein, lipoprotein (a) and apolipoproteins A-1 and B were determined. RESULTS--No changes occurred with diet and placebo, but pravastatin at a daily dose of 10 mg, reduced significantly cholesterol level (7.22 per cent) LDL-cholesterol (13.08 per cent) and increased HDL-cholesterol (7.8 per cent). The results were better with 20 mg, achieving a reduction of (28.21 per cent) in cholesterol, (36.88 per cent) in LDL-cholesterol, (17.06 per cent) in apo B level and an increase of (10.06 per cent) in HDL-cholesterol. The smaller effect observed with the more commonly used dosage (10 mg/day) was most probably due to the characteristics of the sample with already established hypercholesterolemia, being thus dependent of higher concentrations of medications, as observed in previous treatments in our outpatient clinic. Side affects with this drug were rare. No biochemical changes were observed that would interrupt the continuation of therapy. CONCLUSION--Pravastatin was well tolerated and promoted favorable changes in the total cholesterol, LDL, apo B and cholesterol/HDL and LDL/HDL ratios of primary hypercholesterolemic patients

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