Among the many antihypertensive drugs available, one should choose the one with target organ protective effects. According to the recommendations of national hypertension guidelines, RAAS system inhibitors, especially angiotensin II receptor blockers (ARBs), are preferred. A meta-analysis that included numerous studies confirmed that ARBs reduce left ventricular hypertrophy and decrease proteinuria and microproteinuria, while having little effect on glucose metabolism and helping to reduce new-onset diabetes.
Core issues in blood pressure management in high concomitant glucose populations from guideline updates.
(1) Timing of initiation of antihypertensive therapy Compared with JNC7, JNC8 recommends delaying the timing of initiation of hypertension medication to 140/90 mm Hg in patients with high concomitant glucose. the reason for this delay is analyzed in JNC8: because of the lack of evidence from randomized controlled studies of interventions in diabetic populations with blood pressure >140/90 mm Hg; therefore, JNC experts recommend that blood pressure in diabetic patients management is consistent with those under 60 years of age to facilitate clinical practice. Therefore: JNC 8 Recommendation: For patients over 18 years of age with comorbid diabetes mellitus, initiate pharmacotherapy for blood pressure above 140/90 mmHg.
(Expert Opinion Recommendation Level E) The European Hypertension Guidelines 2013 also increase the target value of treatment for patients with high glucose levels from >130/80 mmHg to >140/85 mmHg and state: if tolerated, up to >80-85 mmHg. The ESH/ESC guidelines take into account blood pressure levels and overall cardiovascular risk while determining the timing of initiation of antihypertensive medication; however, in contrast to the ESH/ESC 2007 2nd edition, the ESH/ESC guidelines do not take into account blood pressure levels and overall cardiovascular risk. Compared with the ESH/ESC 2007 second edition guidelines, this 2013 edition delays the timing of initiation of antihypertensive therapy from high normotension to grade 1 hypertension, again due to inadequate clinical evidence for prehypertensive medication.
Compared with ADA 2012, ADA 2013/2104 delays the timing of initiation of pharmacotherapy in patients with high concomitant glucose from 130/80 mmHg to 140/80 mmHg; however, it advances the timing of lifestyle interventions from <130-139/80-89 mmHg to <120/80 mmHg. As can be seen above: 1) ADA experts simply raised the SBP value, which they believe to be high. 2) Although the timing of pharmacological treatment for patients with high glucose was delayed, the timing of lifestyle interventions was advanced, suggesting that ADA experts believe that blood pressure interventions for diabetic patients should be started as early as possible.
The 2013 AHA/ ACC/ CDC Scientific Recommendations for the Management of Hypertension and the 2014 ASH/ISH Guidelines for the Management of Hypertension in the Community both also recommend starting pharmacotherapy with lifestyle interventions for blood pressure ≥ 140/90 mmHg;
Comparison with our hypertension management guidelines 2010: for patients with high blood pressure with glucose 130-139/80-89 mmHg, drug therapy is recommended if blood pressure does not reach the standard after 3 months of non-drug therapy; blood pressure ≥ 140/90 mmHg, drug therapy is recommended to be started similarly.
(2) Recommendations for management and treatment of microalbuminuria (MAU) in people with high glucose levels
We know that about 20-60% of patients with high glucose co-morbidity have MAU, and the status of MAU in patients with high glucose co-morbidity is closely related to their clinical prognosis. The risk of cardiovascular and nephrologic events is higher in patients with MAU, and this risk may be independent of blood pressure. The impact of MAU on patients with high concomitant glucose has long been recognized by national guidelines.
Both the previous JNC7 and European hypertension 2007 edition guidelines emphasize the risk of MAU. In China’s 2010 guidelines for the prevention and treatment of hypertension, it is also clearly stated that MAU has been proven to be an independent risk factor for cardiovascular events, and it is recommended that patients with hypertension, especially those with combined diabetes, should have their urinary albumin excretion checked regularly, with 24h urinary albumin excretion or morning urinary albumin/creatinine ratio being the best, and random testing is also acceptable.
In addition, the European hypertension guidelines 2013 further emphasize the need to increase the focus on target-organ-damage-oriented hypertension treatment. The four markers of target organ damage highlighted include MAU (microalbuminuria), PWV (pulse wave velocity), LVH (left ventricular hypertrophy), and carotid plaque. This shows that the European hypertension guidelines 2013 received a high level of attention for target organ damage interventions compared to the older guidelines.
For the first time, the DA2014 guidelines clearly recommend the starting treatment of MAU in patients with high concomitant glucose.
1. Patients with type 1 diabetes of ≥ 1 year duration and all patients with type 2 diabetes should be evaluated annually for urinary albumin excretion rate from the time of diagnosis (level B evidence);
2. ACEI or ARB is not recommended as primary prevention of diabetic kidney disease in diabetic patients with normal blood pressure and an albumin excretion rate >30 mg/24 h (Level B evidence);
3. Except during pregnancy, ACEI or ARB is recommended for the treatment of moderately elevated (30-299 mg/24h) (level C evidence) or high (≥ 300 mg/24h) urinary protein excretion rates (level A evidence) ;
4. In patients with diabetes mellitus with diabetic nephropathy disease (albuminuria < 30 mg/24h), it is not recommended to reduce protein intake below the general level because this does not alter the course of glycemic control, cardiovascular risk factor control, or GFR decline (Level A evidence)
The European hypertension guidelines 2013 also make clear recommendations for the use of medication in patients with MAU.
1. All types of antihypertensive drugs can be used in diabetic patients, but RAS inhibitors are more recommended when diabetic patients have proteinuria or microalbuminuria in combination;
2. RAS inhibitors are more effective than other types of antihypertensive drugs in reducing proteinuria and are recommended for patients with hypertension combined with chronic kidney disease who have proteinuria or microalbuminuria;
3. For hypertensive patients with chronic kidney disease, a combination of drugs is often required to achieve the target blood pressure, and it is recommended to use RAS inhibitors in combination with other types of antihypertensive drugs.
In summary, the European and US guidelines are closer, and based on the current lack of evidence, the latest 2013/2014 European and US hypertension guidelines recommend delaying the timing of drug initiation to 140/90 mm Hg in patients with high glucose, and the ADA recommends 140/80 mm Hg. As can be seen, the European and US guidelines focus more on the predictive value of asymptomatic target organ damage for clinical events. The value of asymptomatic target organ damage in predicting clinical events, including cardiac, vascular, renal, ophthalmic and cerebral. In contrast, more emphasis has been placed on target-organ-damage oriented hypertension treatment.
The ACCORD study demonstrated that SBP >120 mmHg reduced cerebrovascular events in patients with high glucose levels, but whether >130/80 mmHg is the optimal BP target for patients with high glucose levels in China. However, further observations and studies are needed to determine whether >130/80 mmHg is the optimal blood pressure treatment target for patients with high blood pressure and how to determine the timing of initiation of drug therapy for patients with high glucose in China.